Lagomorpha Flashcards

Question

Describe rabbit teeth type

Answer 1

• Rabbit teeth are elodont (continuously growing), aradicular (open-rooted), and hypsodont (long-crowned)

Answer 2

Uterine adenocarcinoma

Answer 3

Afghan pikas in human care

Answer 4

• Fipronil (Frontline) – Highly toxic, young rabbits more susceptible. Wt loss, diarrhea, seizure.

Answer 5

Endometrial venous aneurysm Ddx uterine adenocarcinoma

Answer 6

Myxomatosis: - leporipoxvirus, from Europe and spread to N. American rabbits (Brush rabbit, Silvilagus bachmani), causes cutaneous fibromas on lips, feet or base of ears but does not cause systemic disease like in domestic rabbits - transmission via blood feeding arthropods, contact, fomites, discharges. - Domestic rabbits (O. cuniculus) – eyelid, ear, head, anogenital swelling and nasal discharge, nodules on head and body - Means of rabbit control in Australia, vaccines in Europe - Tx supportive and unsuccessful Cottontail rabbit papillomavirus (Shope papilloma virus) - oncogenic DNA virus, Papoviridae - arthropod transmission - red hairless warts that are highly keratinized, on head, neck and shoulders - Affects wild cottontails, hares, and jackrabbits. Domestic rabbits get lesions on hairless areas like ears and eyelids. - Can progress to SCC (in domestic rabbits usually). - Can regress if immunocompetent. Rabbit fibroma virus (Shope fibroma): - leporipoxvirus, natural host is eastern cottontail, Oryctolagus - occasionally infected, arthropod transmission. - Young rabbits worse affected than adults. - Large wart like tumors on face, feet, and legs Hernandez Wildlife Book

Answer 7

Di Girolamo, N., Toth, G., & Selleri, P. (2016). Prognostic value of rectal temperature at hospital admission in client-owned rabbits. Journal of the American Veterinary Medical Association, 248(3), 288-297. * Rabbits with hypothermia had significantly higher mortality risk, compared with normothermic and hyperthermic rabbits. * For each 1 deg C (2 deg F) decrease in admission rectal temp, the odds of death were doubled. * Hypothermic rabbits having odds of death 5x the odds for rabbits without hypothermia. * Rabbits with hypothermia at admission had a risk of mortality 3x vs rabbits without hypothermia. * Age, suspected presence of systemic dz, presence of GI stasis were associated with a significantly increased mortality rate. * Rabbits that had not defecated in 12 hours prior to admission had odds of dying 2x vs other rabbits.

Answer 8

Wright, L., & Mans, C. (2018). Lateral rhinostomy for treatment of severe chronic rhinosinusitis in two rabbits. Journal of the American Veterinary Medical Association, 252(1), 103-107. * Lateral rhinotomy aka pararhinostomy * Accesses maxillary sinus versus nasal cavity * Facies cribrosa - porous region of maxillary bone located halfway between medial canthus of eye and ipsilateral naris * Avoid iatrogenic damage to infraorbital neurovascular bundle * Avoids need to penetrate the relatively thick nasal bone (as in dorsal approach) * May be associated with fewer perioperative complications (hemorrhage, premature closure of the ostium, avascular necrosis of the bony flap, poor cosmesis)

Answer 9

Sasai, H., Fujita, D., Seto, E., Denda, Y., Imai, Y., Okamoto, K., ... & Sasai, K. (2018). Outcome of limb fracture repair in rabbits: 139 cases (2007–2015). Journal of the American Veterinary Medical Association, 252(4), 457-463. • Most common fracture sites: tibia \> femur \> radius \> humerus * Tibial fractures healed well with type II ESF +/- IM pins * Time to healing same between open and closed fractures * Percentage of complete healing was higher in closed fractures (100%!) • Distal limb fractures (metacarpals, metatarsal, phalanges) healed well with external coaptation

Answer 10

Gleeson, M. D., Sanchez-Migallon Guzman, D., & Paul-Murphy, J. R. (2019). Clinical and pathological findings for rabbits with dystocia: 10 cases (1996–2016). Journal of the American Veterinary Medical Association, 254(8), 953-959. * Cause of dystocias: * Fetal-maternal mismatch or fetal macrosomia (n = 4) 🡪 most common * Uterine inertia (n = 2) * Fetal death or mummification (n = 1) * Stress-induced abortion (n = 1) * Unknown (n = 2) * Potential risk factors * More common in \< 4 yo primiparous does * No seasonal or breed trend * NONE of the does had other underlying repro disease * Most were small breeds (6 rabbits weighed \<2kg) – suspect small size contributed * Conclusion * Rabbits more likely to have obstructive dystocia from fetal macrosomia and secondary uterine inertia than other causes * Young, primiparous does common * Medical management alone was successful for many rabbits and should be considered, esp when surgical management not possible

Answer 11

Zoller, G., Di Girolamo, N., & Huynh, M. (2019). Evaluation of blood urea nitrogen concentration and anorexia as predictors of nonsurvival in client-owned rabbits evaluated at a veterinary referral center. Journal of the American Veterinary Medical Association, 255(2), 200-204. * Higher mortality rate over a 7 day period for rabbits with hyponatremia \< 129 mEq/L. * Hyperglycemia \> 20 mmol/L observed in rabbits with life-threatening diseases. * Rabbits with intestinal obstruction had significantly higher BG than w/stasis. * Rabbits seropositive for E. cuniculi had higher BUN than seronegative rabbits, but both were within reference. * A study looking at anorectic rabbits showed BUN \> 27 mg/dL had higher mortality rate. * A high BUN concentration increased the risk of nonsurvival over a 15 day period for client-owned rabbits, particularly those with anorexia. Hypothermia: Takeaway: **Hypothermic rabbits < 98 deg F on presentation are 5 times more likely to die.** No hematologic or biochemical variable were associated with outcome in this study. Oparil, K. M., Gladden, J. N., Babyak, J. M., Lambert, C., & Graham, J. E. (2019). Clinical characteristics and short-term outcomes for rabbits with signs of gastrointestinal tract dysfunction: 117 cases (2014–2016). Journal of the American Veterinary Medical Association, 255(7), 837-845.

Answer 12

Cox, T. E., Liu, J., de Ven, R. V., & Strive, T. (2017). Different serological profiles to co-occurring pathogenic and nonpathogenic caliciviruses in wild European rabbits (Oryctolagus cuniculus) across Australia. Journal of wildlife diseases, 53(3), 472-481. * RCV-A1 prevalence was highest in areas with higher rainfall and better breeding * The high prevalence of young rabbits (not susceptible to RHDV) may account for lower mortality * Also possible that those young rabbits get exposed to RCV-A1 which helps reduce mortality * RCV-A1 antibodies alone are not protective, but the cell-mediated mechanism are suggested to reduce mortality Take Home: • Rabbits in wetter areas have higher prevalence of RCV-A1 (nonlethal) which may confer immunity to those areas The proportion of rabbits with RHDV antibodies increased significantly at sites where RCV-A1 antibodies were present (chi-square, a=0.1, P\<0.001). Evidence that preinfection of RCV-A1 may lead to a higher proportion of sampled rabbits with antibodies to both viruses was found at only one site.

Answer 13

Cabot, M. L., Eshar, D., & Beaufrère, H. (2020). Utility of commercially available reagent test strips for estimation of blood urea nitrogen concentration and detection of azotemia in pet rabbits (Oryctolagus cuniculus) and ferrets (Mustela putorius furo). Journal of the American Veterinary Medical Association, 256(4), 449-454. - Fair agreement between categories test strip and analyzer - Precision for detecting azotemia super high in both - Accuracy better better in ferrets - High sensitivity, lower specificity in rabbits (more false positives) - Test strips occasionally higher than analyzer - Lower sensitivity, high specificity in ferrets (more false negatives) But 100% specificity in ferrets - Test strips provided reasonable estimates of BUN concentration but, for rabbits, were more appropriate for ruling out than for ruling in azotemia because of false-positive test strip results. False-negative test strip results for azotemia were more of a concern for ferrets than rabbits. Testing with a biochemical analyzer remains the gold standard for measurement of BUN concentration and detection of azotemia in rabbits and ferrets.

Answer 14

Schnellbacher, R. W., Divers, S. J., Comolli, J. R., Beaufrère, H., Maglaras, C. H., Andrade, N., ... & Quandt, J. E. (2017). Effects of intravenous administration of lidocaine and buprenorphine on gastrointestinal tract motility and signs of pain in New Zealand White rabbits after ovariohysterectomy. American journal of veterinary research, 78(12), 1359-1371. * Increased GI motility, food intake, fecal output, and number of normal behaviors * Decreased blood glucose levels, lower heart rate overall * Both groups had weight loss after surgery * Pain scores did NOT differ between groups * No rabbits required rescue protocol. Suggests both drugs provided sufficient analgesia. Takeaway: Lidocaine, provided as a CRI for 48 hours post-ovariohysterectomy, appeared to provide improved analgesia as compared to buprenorphine. Lidocaine treated rabbits had fewer signs of pain, more food intake and fecal production, and lower blood glucose concentrations.

Answer 15

Principati, S. L., Keller, K. A., Allender, M. C., Reich, S., & Whittington, J. (2020). Prognostic indicators for survival of orphaned neonatal and juvenile eastern cottontail rabbits (Sylvilagus floridanus): 1,256 Cases (2012–17). Journal of wildlife diseases, 56(3), 523-529. Chance of mortality in orphaned rabbits increases with: - Singleton - Skin injuries - Multi-organ disease - Neurologic signs - Treatment prior to presentation - Not affected by body weight, respiratory signs, dehydration - Common bacteria from predator bite wounds: Pasteurella, Staphylococcus, Enterococcus, Bacillus, Streptococcus Conclusions: Chance of survival was lower in rabbits with singleton, any integument signs, multi-organ disease, neuro signs, treatment prior to presentation.

Answer 16

Assessment of reported uterine lesions diagnosed histologically after ovariohysterectomy in 1,928 pet rabbits (Oryctolagus cuniculus). Settai K, Kondo H, Shibuya H. Journal of the American Veterinary Medical Association. 2020 Nov 15;257(10):1045-50. Most common signs of uterine neoplasia in rabbits = hematuria, serosanguinous vaginal discharg Diseases most associated with signs: Endometrial adenocarcinoma/hyperplasia Most common uterine neoplasia = endometrial adenocarcinoma Holland lops had higher odds than Netherland dwarfs Age at OVH positively associated with incidence of endometrial adenocarcinoma Most common non-neoplastic lesion = endometrial hyperplasia Conclusions: Endometrial adenocarcinoma is the most common neoplasia of rabbits uterus, which was associated with a later age of spay.

Answer 17

Comparison of intra− and postoperative variables between laparoscopic and open ovariectomy in rabbits (Oryctolagus cuniculus) Kabakchiev C, Singh A, Dobson S, Beaufrère H. American Journal of Veterinary Research. 2021 Mar;82(3):237-48. Laparoscopic ovariectomy in rabbits (compared to traditional ovariectomy) had: Longer surgical time and anesthesia time Smaller incision More difficulty removing the right ovary More complications (intestinal perforation, superficial incisional dehiscence, SC emphysema, seroma) Traditional ovariectomy also had superficial incisional dehiscence No post op differences (food consumption, feces, weight, vitals, BG, cortisol, palpation, grimace, ethograms) Conclusions: Longer surgery and anesthesia times and more complications for laparoscopic ovariectomies in rabbits but no difference from traditional post-op monitoring.

Answer 18

Comparison of the use of a vessel-sealing device versus ligatures for occlusion of uterine tissues during ovariohysterectomy or ovariectomy in rabbits (Oryctolagus cuniculus) Euan J. McLean, Andrew P. Woodward, Stewart D. Ryan Am J Vet Res 2020;81:755–759 Key Point: Vessel sealing device was effective at uterine horns but NOT at the cervical-vestibule junction (CVJs) Very poor seal in some CVJs VSD used in this study got good seals at the uterine horns (UHs), but not the CVJs. Conclusions: Do not use a vessel sealing device to seal the cervical-vaginal junction in rabbits where that junction is \>10 mm in diameter. May be able to use safely to seal uterine horns.

Answer 19

Computed tomographic findings of dental disease in domestic rabbits (Oryctolagus cuniculus): 100 cases (2009–2017) Artiles CA, Sanchez-Migallon Guzman D, Beaufrère H, Phillips KL. Journal of the American Veterinary Medical Association. 2020 Aug 1;257(3):313-27. Most common breed = Dwarf miniature Most common sex = male Most common clinical signs: ocular discharge \> mandibular/maxillary masses \> hyporexia \> nasal discharge Dental disease was most common in older rabbits Common findings (in order of prevalence): Apical elongation Sharp dental points Periodontal ligament space widening Periapical lucencies (often with abscesses; mandibular \>\> maxillary) Tooth resorption Incisor malocclusion (often with premolar/molar elongation in dwarf-mini breeds) Most common tooth = Mandibular PM3 Conclusions: The most common dental disease syndrome was a dwarf miniature rabbit with ocular discharge, apical elongation and sharp dental points, especially of mandibular premolar 3.

Answer 20

Investigation of a maxillary nerve block technique in healthy New Zealand White rabbits (Oryctolagus cuniculus) Peña T, Campoy L, de Matos R. Investigation of a maxillary nerve block technique in healthy New Zealand White rabbits (Oryctolagus cuniculus). American Journal of Veterinary Research. 2020 Nov;81(11):843-8. Key Points: Landmarks of maxillary nerve block in rabbits: Facial tuber Zygomatic arch Needle enters skin ventral to zygomatic arch and aims dorsocaudally Maxillary nerve block was effective for ~60 min Not affected by volume No adverse effects Conclusions: Maxillary nerve block in rabbits can be performed with this new technique.

Answer 21

Ozawa, S. M., Hawkins, M. G., Drazenovich, T. L., Kass, P. H., & Knych, H. K. (2019). **Pharmacokinetics of maropitant citrate in New Zealand White rabbits (Oryctolagus cuniculus).** American journal of veterinary research, 80(10), 963-968. Key Points: - Mild local reactions at some SC injection sites (most common adverse effect) - Hyperexcitability and/or tachypnea in some rabbits for 5-15 minutes after IV or SC injection - Low bioavailability (60%) compared to dogs or cats (\>90%) - Levels similar to in dogs for 24 hours Conclusions: Rabbits have similar maropitant PK to dogs but had local injection site reactions and transient hyperexcitability and/or tachypnea.

Answer 22

Gardhouse, S., Guzman, D. S. M., Cox, S., Kass, P. H., Drazenovich, T. L., Byrne, B. A., & Hawkins, M. G. (2017). **Pharmacokinetics and safety of ceftiofur crystalline free acid in New Zealand White rabbits (Oryctolagus cuniculus)**. American journal of veterinary research, 78(7), 796-803. Key Points: - Ceftiofur: 3rd gen cephalosporin - Action on gram+ and gram- (E. coli Proteus, Salmonella, Klebsiella, shigella, Enterobacter) -- *Does NOT work on Pseudomonas aeruginosa* but other 3rd gen cephalosporins do work - Time dependent - Inhibits bacterial cell wall synthesis = bactericidal - Adverse effects of CCFA injection = bruising and SQ nodule formation at injection site - CFFA in rabbits (compared to other species) had: -- Faster Tmax -- Higher Cmax and AUC -- CCFA in rabbits (compared to ceftiofur sodium) had higher T1/2, AUC Cmax, Tmax -- Above target MICs for 24-72h Conclusions: - Ceftiofur at 40mg/kg given q24-72h in rabbit with side effects at injection site in 50%. - Cmax,Tmax, and AUC higher for rabbits than other sps.

Answer 23

J Am Vet Med Assoc 2021;258:977–982 Comparison of plasma total solids concentration as measured by refractometry and plasma total protein concentration as measured by biuret assay in pet rabbits and ferrets David Eshar dvm Kacey L. Solotoff dvm Hugues Beaufrère dvm, phd * Plasma TS values overestimated plasma TP for both ferrets and rabbits * These two methods can not be used interchangeably for rabbits and ferrets since refractometer overestimated biuret values on average for both species * Cholesterol, glucose, BUN, hemolysis and lipemia had significant effects on the magnitude of bias for ferrets * BUN had a significant impact on measurement bias in rabbits Take home: • Plasma TS concentration as measured by refractometry overestimated and failed to adequately estimate the plasma TP concentration as measured by biuret assay for both ferrets and rabbits

Answer 24

**Chapter 13: Gastrointestinal Physiology of Rabbits – summarized by ADW** * **Monogastric, hindgut-fermenting herbivore w/ digestive physiology reliant on cecotrophy** * Efficient digestion of fibrous vegetation w/o needing to store large volumes of food w/in body * GIT: simple stomach, well-developed cecum, particle-dependent separation mechanism w/in proximal colon * Digestible fiber particles/solutes not immediately digested/absorbed enter colon & selectively retained as substrates for microbial fermentation w/in cecum * Nondigestible fiber rapidly expelled * **Cecotrophy** (ingestion of packets of cecal contents) enhances nutrition of forage-based diet **_Ingestion of Food_**: intake driven by food’s energy density & gastric fill * Original wild rabbits had seasonal diets low in energy density w/ grasses dominating * Seek more energy-dense diets when offered a choice * Palatability, variety also important * Adults feed \>20X in a 24-hour cycle (short sessions of 2-8 g food consumed over 4-6 min) * **Crepuscular**: more frequent feeding around light/dark cycle transitions * Olfactory/tactile information about food is important (eyes laterally positioned so rabbits do not see their food as they eat) * Healthy dentition relies on food choice \> **upper incisors grow as fast as 2mm/week** * Incisors slice food into smaller pieces \> premolars/molars masticate in lateral grinding motion (also keeps occlusal surfaces in correct alignment) * Large tongue circulates food particles through molar grinding surfaces * Chewing actions up to 120X/min required to breakdown fibrous foods for fermentation **_Stomach_**: simple stomach comprises ~15% GI volume * Cannot vomit (**well-developed cardiac sphincter**) * Hydrochloric acid, pepsin secreted into stomach to initiate digestive process as in other species * Gastric pH varies diurnally but generally **very acidic** compared to other species (postprandially drops to pH 1.0-2.0, rises to 3.0 after ingestion of cecotrophs) \> low pH sterilizes ingesta * Juvenile (preweaned) rabbits have higher gastric pH (5.0-6.5) to promote survival/passage of ingested bacteria \> facilitates establishment of large intestinal flora * Normal stomach contents: hair, food, fluid even after 24 hours fasting/anorexia * Gastric transit time: ~3-6 hours * *Cyniclomyces guttulatas (Saccharomycopsis guttulata)*: symbiotic yeast lines stomach of rabbits & likely proliferates there rather than in cecum/large intestine **_Small Intestine_**: primary site of nutrient digestion/absorption, similar to other monogastrics * Bicarbonate: secreted into proximal SI \> neutralizes acidic digesta leaving stomach * _Duodenum_ enriched w/ enteropeptidase, aminopeptidases, oligosaccaridases, disaccharidases * During developmental transition to solid foods: upregulated host digestive enzymes (pancreatic amylase, lipase; proteases [trypsin, chymotrypsin]; jejunum shifts from lactase to maltase & sucrase) * _Jejunum, ileum_: site of nutrient absorption, digestion/absorption of nutrients from ingested cecotrophs * **Efficient digestion: 80-100% dietary starch & amino acids absorbed by the time they reach the distal ileum** * Nutrient-dense foods w/ high digestibility (e.g. commercial rations) have higher bioavailability than vegetative foods/grasses * Bulk of diet is vegetative forage \> mastication breaks into small particles (cellulose, hemicellulose, lignin, oligosaccharides, protein; all are bound in a biomatrix) \> particles pass through SI largely undigested * Dry matter in distal ileum: ~70% fiber, ~15% nitrogenous * **Rapid SI transit time**: 10-20 min jejunum, 30-60 min ileum * **Ileocolic valve** at distal ileum prevents retrograde motion of ingesta from colon/cecum into ileum **_Gut-associated Lymphoid Tissue (GALT)_**: Peyer’s patches, sacculus rotundus, vermiform appendix * **Peyer’s patches**: lymphoid follicules associated w/ jejunum, distal ileum * 2 unique structures to rabbits: both enriched in lymphoid nodules which are sites of lymphocyte expansion * **Sacculus rotundus** (@ ileocecal junction) * **Vermiform appendix** (@ distal terminus of cecum) * (similar lymphoid follociles present along colon) * GALT roles incompletely understood: provide barrier functions, stimulate oral tolerance, mediate antigen presentation of microbial proteins, influence enterocyte development

Answer 25

**_Large Intestine_**: cecum, colon * _Cecum_: thin-walled, comprises 49% GIT volume, primary site of digestible fiber fermentation * Occupies \>50% abdomen, positioned on the right in a coiled structure * Terminates in a vermiform appendix that secretes water & bicarbonate into cecum for fermentation (also has lymphoid tissue, see above) * _Colon_: contains 4 regions that are structurally/functionally distinct * **Most anterior region (approximately 10 cm) of proximal colon**: longitudinally striated by 3 thick muscular bands (taeniae) interspersed w/ 3 sacculated haustra that provide a high luminal surface area * **Next ~20 cm**: single longitudinal taenia & haustrum * **Fusus coli** (unique to lagomorphs): 4-cm long structure demarcates the proximal & distal colon * Densely innervated, banded circumferentially w/ muscle * Lacks both taeniae & haustra, luminal surface rich in goblet cells * **Distal colon** (80-100 cm long): thin walled, extends from fusus coli to rectum * Luminal surface has short crypts & numerous goblet cells * **Ampilla caecalis coli**: specialized chamber that connects the ileum, cecum, and proximal colon * _Proximal colon_: mechanically separates digested particles by size for either cecal fermentation or fecal excretion * Haustra luminal surfaces lined w/ dense mucosal protrusions called “**warzen**” (or warts) averaging 0.5 cm diameter * Smaller (\<0.3 mm) fiber particles penetrate spaces btwn warzen & preferentially retained along haustra * Larger particles (\>0.3 mm) remain in central lumen * _Complex sequence of contractions separates particles_: * Post-prandial aboral propulsion of larger, nonfermentable particles * Aldosterone mediates resorption of water, potassium, sodium from fibrous material * Muscular fusus coli compacts material into rounded pellets * Additional water, electrolytes, volatile fatty acids extracted during fecal passage thru distal colon * Excreted feces mostly comprised of nondigestible fiber (dry matter, 52.7%) w/ very little water * Indigestible fiber does not contribute to metabolizable energy, but its bulk properties promote GI motility, cellular regeneration, muscle tone, & help regulate microbiota composition **_Hindgut Flora and Fermentation_**: fermentation occurs predominantly in cecum (distal ileum, proximal colon contains microbial populations that may contribute pectinases & xylanases for conversion of soluble fiber) * _Complex microbiota is genetically unique to rabbits_: 1-gram cecal contents contains 10¹⁰-10¹² bacteria, 10⁷ copies of 16S RNA from archaea (prokaryotes) * Microbiota lack eukaryotic protozoa, anaerobic fungi (debatable presence of yeast [*C. guttulatus*] in cecum – these line the stomach); most are new species not previously identified * *Firmicutes* (\>90%) phylum dominates bacterial cecal microbiota (most abundant families: *Ruminococcacaeae* (45%), *Lachnospiraceae* (35%)) * *Bacteroidetes* (4%) * Facultative anaerobes (*Streptococcus* species, *Escherichia coli*) abundant postnatally but largely disappear postweaning * Lack *Lactobacillus* * Adult healthy rabbits have stable cecal community over time * Low interrabbit variability (may be due to genetics or limited diet variability) * **Cecotroph profile reflects cecal environment** (vs. fecal composition more divergent) * Fermentation in cecum coverts forage into energy & nutrient forms * 1-gram of cecal material has 10⁷ CFU cellulolytic, 10⁹-10¹⁰ CFU pectinolytic & xylanolytic bacteria \> cellulose, pectin, hemicellulose can be fermented (pectin, hemicellulose dominates) * Nitrogen sources for microbes: plant proteins, plasma urea * Mucin production by cecal goblet cells modulates microbial growth * Digesta entering cecum from ileum is predominately fiber (70%) & nitrogenous compounds (15%) * Volatile fatty acids (VFAs): typically 75% acetate, 10% proprionate, 15% butyrate; produced via fermentation of plant oligosaccharides by microbial hydrolases * Also produced: ammonia, intermediate organic acids (lactate, succinate, formate), small quantities of gas (H2, CH4, CO2) * Fermentation efficiency: pectin \> hemicellulose \> cellulose * VFAs, organic acids transported to mucosal cells for use by colon, remainder used by liver * VFAs, organic acids are preferred energy source for colon (esp. butyrate) * VFAs contribute 30-50% of basal metabolic needs * Proportion of VFAs varies by time of day, diet, developmental stage * Indigenous intestinal microbiota serves protective role from potential pathogens * *Clostridium* spp. are \<1% to 0.1% total bacterial population of normal rabbits * Energy is limiting factor for cecal microbial population * Dysbiosis: disrupted normal balance of microbiota in gut, from inappropriate therapeutic antibiotics, exposure to pathogenic organisms/toxins, increased glucocorticoid levels (iatrogenic, secondary to stress), GI hypomotility, poor diet (low fiber, high CHO, high protein) * Suckling rabbits only feed for 3-4 min 1-2X/24-hr period \> **rabbit milk is very energy-dense** (8.5 MJ/kg) w/ 10-15% protein, 12-15% lipid, low lactose (5% DM) * Stomach: milk enzymatically converted to curd that is slowly digested over 24 h * Milk is rich in medium-chain triglycerides (esp. octanoic & decanoic acid) which confer antimicrobial properties * Days 4-6: ingestion of maternal hard feces to begin cecal microbiota colonization (facilitated by stomach’s higher pH) * Days 16-18: solid food consumption begins, increases sharply @ day 25 * Weaning @ 5-6 weeks or sooner if mother is pregnant

Answer 26

**_Cecotrophy_**: production actively regulated, occurs in circadian rhythm inverse of food intake & fecal synthesis * Diphasic production, 4 hours after a meal during quiet period * Frequency modulated by age, light cycle, feeding pattern * NOT a response to nutritional stress, it is normal physiologic process to enhance nutrient content of poor-quality foods through reconsumption of fermented digesta enriched w/ microbe-derived nutrients * **Cecotroph = cecal contents compressed into soft pellet (5 mm diameter), coated by mucus; emerge from anus in grapelike cluster & directly consumed from anus w/o chewing** * Unknown what signals initiate cecotrophy (cecal pH? Content of VFA?) * **Fusus coli is “intestinal pacemaker:”** controls segmental, peristaltic, haustral colonic motility \> antiperistaltic contractions minimized to reduce mechanical separation process \> aboral peristaltic waves dominate to propel cecal contents thru proximal colon \> passes thru fusus coli to compress loss cecal material \> goblet cells coat small pellets w/ mucin * Transit time for cecotrophs thru colon: 1.5-2.5X faster than hard feces * Cecotrophs are 34% DM by weight, contains 18% fiber, 30% protein (80% of the protein is microbial in origin), rich microbiota (bacteria 10¹⁰/g DM, some archaea) * Most nutrient richness from microbiota & cecal fermentation of plant forage \> essential amino acids (lysine, threonine, sulfur AA), vitamins (thiamin, riboflavin, niacin, pantothenate, pyrodixine, folate, B12, biotin, vitamin K), minerals from plant matrix (phosphorus, magnesium, iron, copper, zinc) * Cecotroph protein is 10-23% daily AA requirement * Cecotroph reingestion enables nutrient absorption in jejunum/ileum * Stays intact w/in stomach for 3-6 hours, buffers stomach pH (from pH 1.0-1.5 to 3.0) * Lysozyme in cecotroph (from colon) breaks down peptidoglycans in microbial cell walls & releases protein/micronutrients for digestion \> microbes further ferment fiber from cecotrophs * **Small quantities of cecotroph microbiota make it to the cecum \> rabbits w/ cecal dysbiosis may benefit from ingesting health cecotrophs**

Answer 27

**_Motility_**: * _SI_: postprandial motility influenced by autonomic nervous system, hormones, nutritional content (esp. indigestible fiber levels) * Interdigestive phase: **motilin** released from endocrine M cells w/in duodenojejunal mucosa stimulate migrating motor complex \> propels materials aborally, limits bacterial overgrowth * Motilin receptors present in SI, colon, rectum, CNS; absent from cecum * Motilin activity mimicked by motilide pharmacologic agents, macrolide antibiotics (e.g. erythromycin) * _Cecum/colon_: circadian motility pattern for fermentation coordinates cecotropes/feces * Hard feces formation coincides w/ feeding activity * Cecotrope formation is several hours after feeding (typically during rest) * Rhythm influenced by diet, age, reproductive status * Cecum: peristaltic, antiperistaltic waves move from base to apex & back at frequency of 1-2 contractions per minute \> slow waves make backflow \> mixes cecal contents, enhances fermentation * _Proximal colon_: shallow aboral contractions of haustra (13.8-16.2/min) mix digesta & drive particle size separation * Retrograde contractions along single-haustrated colon propel small particles/liquid back to triple-haustrated colon/cecum \> supplies cecal microbiota w/ substrate for fermentation * Migrating segmental contractions (at same time as retrograde contractions) propel large particles aborally to fusus coli for concentration/excretion * Haustral contractions are suppressed when cecotrophs are produced \> giant rhythmic contractions stimulated by prostaglandins expel cecal contents through proximal colon for processing into cecotrophs

Answer 28

**_Nutritional Requirements_** * Exact nutrient requirements unknown * Nutritionally adequate diet has (A) fiber substrate for cecal fermentation, GI motility and (B) meets nutrient/energy needs in excess provided by fermentation/cecotrophy (these are nutritionally inadequate for energy, protein, micronutrients) * Diet should promote normal foraging behavior throughout the day **_Energy Requirements_**: influenced by age, body size, environment * Estimates: maintenance 400 kJ/day/kg (96 kcal/day/kg); growth/pregnancy/lactation 430 kL/day/kg (103 kcal/day/kg) * Not a linear relationship between energy requirement and body weight * **Smaller breeds require more energy per kg** (higher basal metabolic rate, smaller gut capacity) * Environmental temperatures above/below thermoneutrality (21C-25C) increase/decrease energy intake, respectively * Typically self-regulate food intake in response to energy status, but boredom & need for gastric fill promotes overeating * Low density foods (forage) should predominate & energy-dense foods (pellets) restricted for rabbits kept in cages/indoor (low energy expenditure environment) to reduce obesity **_Protein_**: required for growth/lactation, maintenance, fur production * Requirements: 12-14% maintenance, 18% lactation, 16-18% angora breeds (constant fur production) * Essential amino acids: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine * From diet & ingested cecotrophs (28% protein) * Essential AA from cecotrophs do not meet requirements if dietary protein quality is poor * Cereal grains (corn, barley, oat, rye) are low in lysine/methionine, so commercial diets add complementary protein sources (e.g. alfalfa) * Urea cycle supplies sufficient arginine * Forage contains sufficient sulfur-containing amino acids * SI protein digestion is efficient for forages (alfalfa 72-83%, fresh grass 78%) * Poor utilization of nonprotein nitrogen \> **dietary urea can be toxic** * Voluntary regulation of cecotrophy to balance protein intake \> **more uneaten cecotrophs occur if fed a high protein diet** * **Excess dietary protein elevated plasma urea, cecal ammonia content \> raises cecal pH \> environment permissive for *Clostridia, Escherichia* overgrowth** **_Carbohydrate (CHO)_**_:_ major source of energy, very efficient digesters of starch/simple sugars * Ileal digestibility averages 97% (ranges: 93% wheat, 99% maize starch) * Lower starch digestibility in young rabbits \> digestibility rises as pancreatic amylase levels increase thru 12 weeks of age * **High intakes of rapidly fermentable CHO & reduction of fiber intake increases enteritis risk** * Rabbits may tolerate greater starch intakes than currently recommended (150-155g/kg DM) if fiber intake \>10-12% * Exception: young rabbits have greater ileal flow of starch and high CHO will increase risk for enteritis **_Fiber_**: commercial pellets should have 20-25% dietary fiber (pet/maintenance) or 18-20% (production) * Need both digestible & nondigestible fibers * **Long-strand fibers** (e.g. hay) promote healthy dentition (keeps molar surfaces in proper occlusion), propel ingested fur thru GIT (reduces trichobezoar risk), stimulates gut motility & enterocyte turnover * Fermentation of predominantly digestible fiber (& some cellulose) provides 30-50% daily energy * Volatile fatty acids are preferred energy source for colon * Fiber digestibility is function of fiber source, diet composition, breed * Digestibility varies from 10-27% cellulose/lignins, 11-46% hemicellulose/pectins * Lower efficiency than other hindgut fermenters (horses) * Cecotrophy provides vitamins, essential amino acids * Fiber promotes microbial diversity, reduces enteritis risk * Ad libitum hay satisfies frequent foraging need (prevents obesity, fur-pulling behavior) * Low fiber diets associated w/ increased GI disorders, death, reduced voluntary food intake **_Fat_**: small % of daily calories, exact requirement unknown \> 20 g/kg (2%), do not exceed 30-35 g/kg (3-3.5%) * Similar triglyceride digestion as other nonruminants (pancreatic lipases, bile acids, duodenal absorption of micelles) * Fats promote absorption of fat-soluble vitamins, provide essential fatty acids (ESA), improve palatability * ESA (linoleic, linolenic, eicosapentanoic, docosahexaenoic) are precursors for eicosanoid hormones that modulate inflammation, blood pressure, thrombosis * ESA requirement unknown, emphasize omega-3 over omega-6 * **Avoid high fat diets: prone to obesity, hepatic lipidosis, atherosclerosis** **_Vitamins and Minerals_** (see Table 13.1 at the end): only production values known, maintenance requirements may be slightly lower * _Vitamins_ * Cecotrophs provide vitamin K, most B vitamins * Vitamin D from sun-cured hay (as ergosterol) or direct sunlight exposure (as cholecalciferol) * Vitamin E in alfalfa meal, seed oils * Vitamin A efficiently synthesized from plant carotenoids (rabbits do not store carotenoids) * Toxicosis more likely than deficiency (from feed misformulation, carrot overconsumption) * Vitamin C is synthesized (no dietary source needed) * Supplementation above requirements increases risk for toxicosis (no health improvements shown) * Deficiencies uncommon: poor diet quality, intestinal parasites, failure to consume cecotrophs, chronic disease * _Minerals must be from diet_ * Microbial phytases in cecum significantly improve bioavailability of plant-based calcium/phosphorus & divalent metals (magnesium, copper, zinc, manganese) * **Intestinal calcium absorption is directly proportional to intake, independent of phosphorus/vitamin D \> serum calcium directly reflect dietary calcium** * Vitamin D, PTH regulate serum calcium \> excess calcium secreted thru urine (instead of bile) * Alkaline urine (pH 8.2) precipitates urinary calcium as insoluble white/yellowish carbonate deposits (can be seen grossly) \> excess calcium increases risk of urolithiasis, soft tissue calcification * Continually growing teeth have high calcium demand \> inadequate calcium intake may increase risk for dental disease * Do not completely remove calcium from diet since calcium will be drawn from bones/teeth to meet plasma/cellular needs * Salt/mineral lick unnecessary (minerals provided by forage, vegetables, pelleted chows)

Answer 29

**_Dietary Components_** **_Hay_**: feed ad libitum, refresh daily * Satisfies satiety needs, has low energy density, promotes gut motility & cecal fermentation, reduces risk for dental disease * 2 broad classes: leguminous, grasses * Leguminous hays (alfalfa, clover): for lactating does, young growing rabbits * Higher protein (15-25%), higher calcium (1.2-1.5%) * May increase risk of cecotroph overproduction (from higher protein) and urolithiasis (from calcium) * Grass hays (brome, fescue, orchard, rye, timothy): for mature/nonbreeding rabbits * Lower energy & nutrient density than leguminous hays * Nutrient content varies w/ growth stage at time of harvest (fiber content increases & nutrient content decreases as plant matures) * Typical: 7-15% protein, 25-35% fiber * First-cut hays generally higher in fiber * Second-cut hays generally higher in protein, lower in fiber * Do not offer: * Grain-based hays (oat, wheat, barley) \> contain seed heads \> encourages poor dietary habits & weight gain * Silage \> reduces growth & food intake * Straw \> poor nutrient content can cause deficiencies (anecdotal: straw-only diet for 2-3 days may help reestablish cecal microbiota & reduce enteritis risk) * Quality hay smell fresh, is not musty * Store in airtight container away from sunlight, heat, moisture **_Fresh Vegetables (“Greens”)_**: 2 cups varied fresh vegetables or edible plants for a 2.3 kg (5 lbs) rabbit * Many (but not all) micronutrients & modest fiber provided by fresh vegetables/leafy greens * High water content of greens provides satiety w/o many calories * Introduce fresh greens, novel items gradually to allow gut microbes to adapt & avoid GI dysbiosis * Suitable: green & red leaf & romaine lettuces (not iceberg), celery leaves, chard, chicory, endive, escarole, radicchio, spring greens, green & sweet red peppers, carrots (small quantities), beets, radish tops, herbs (cilantro, fennel), broccoli, brussels sprouts, cauliflower, cabbage * Occasional wild plants: bramble, chickweed, fresh clover, dock, plantain, sunflower, wild strawberry & raspberry leaves, violet, yarrow * High calcium intake in some rabbits promote urolithiasis \> offer high calcium greens in moderation or not at all (dandelion, collard, mustard greens, kale, bok choy, spinach, watercress, basil, mint, parsley) * Offer rotation of veggies for nutrient variety & to prevent overfeeding of veggies w/ high calcium, carotenoid, CHO content * Fruit: offer sparingly if at all \> high sugar content \> potential CHO overload in hindgut & obesity * Small amount 1-2 times weekly is OK (1 Tbsp for a 2.3 kg [5lbs] rabbit) * Store perishable veggies/greens in a fridge & rinse w/ water before serving to remove contaminants **_Commercial Mixes and Pellets_**: ¼ cup BID per 2.3 kg (5 lbs) * _Maintenance-style diet for adult nonbreeding rabbits_: high fiber (20-29%), low protein (13-14%), low calcium (\<1%), low digestible energy (1.6 kcal/g) \> reduces risk for obesity, cecotroph overproduction, urolithiasis * vs. production diets: lower fiber (18-20%), higher protein (16-18%), higher calcium (\>1.5%), higher digestible energy (3.8 kcal/g) * Available diets are timothy-based or timothy/alfalfa blend * Alfalfa based acceptable if fed in restricted quantities * Concentrates: offer ad libitum to growing/pregnant/lactating or rabbits that have difficulty maintaining weight * Adult nonbreeding: offer pellets in limited quantity \> reduces obesity, encourages hay consumption * Serving sizes based upon size, age, activity level, and pellet energy density * Decrease serving size in obese rabbits: **safe rate of body mass loss = 100 g/week** * A vegetable/greens meal substitutes for a pellet serving but **pellets necessary for nutritionally complete diet** * _Nutrient composition of commercial pellets variable_: * **Long fiber particles (\>0.5 mm) stimulate gut motility, small particles (\<0.3 mm) lead to increased gut retention time, reduced gut motility, enteritis** * Optimal pellet size: 0.63 cm long, 0.47 cm diameter * Extruded grain components enhance digestibility * Antioxidants (vitamin E, benzoic acid) prevent rancidity * Prebiotics/probiotics unnecessary * Store pellets in cool, airtight containers in pest-free locations and use before manufacturer’s expiration date * Mixed/muesli-style rations have flaked/rolled grains, nuts, extruded biscuits w/ high energy density \> **do not offer** \> selective feeding & nutrient imbalances * Rabbits favor the flaked peas/corn (high starch, low calcium/fiber \> obesity, enteritis, dental disease) * Complete mixture of ingredients rarely consumed * Some ingredients (e.g. locust beans) implicated in GI obstruction **_Other Feed Items_**: * Do not feed food high in digestible CHO/fat \> enteritis, obesity, picky eating * e.g. beans, peas, corn kernels, bread, breakfast cereal, nuts, seeds, chocolate, high-sugar fruits (bananas), some commercial “treats” * OK as treats: carrots, low-sugar fruits (strawberries, raspberries), timothy-based treats with no added sugar **_Water_**: fresh, clean water available always (10% loss of body water is fatal) * **Water consumption varies: 0.25-0.57 L/day, or 120 mL/kg** * Intake influenced by temperature & diet * Water-rich foods (vegetables) reduce water intake * Offer in bowl/bottle \> drink more from bowl \> promotes urinary calcium excretion * Ceramic crocks: easy to clean, unlikely to tip over * Bottles less likely contaminated w/ spilled food/feces, might reduce risk of moist dermatitis on dewlap (intact females) * Check bottles/automatic watering systems daily for air bubbles blocking water flow **_Summary of Dietary Recommendations_** * Diet of nonbreeding adult pets differ from production rabbits * Lactation, pregnancy, growth, recovery from illness have added nutrient demands \> concentrate pellets & leguminous hays (e.g. alfalfa) * Most common mistake of owners: overfeeding energy-dense pellets/treats, lack of hay * Unlimited access to hay (helps dentition, satisfies constant foraging need) * Grass hays \> leguminous hays, but any hay better than no hay * High-quality pellet in restricted quantities proportionate to age, size, activity level * **Start w/ ½ cup per 2.3 kg (5 lbs) BW & adjust for pellet’s energy density** * Adults: timothy based/blend w/ _\>_14% protein, 0.5-1% calcium, 20-29% fiber * Avoid pellet-free diets (hay- & vegetable-only diets cannot meet all nutrient requirements) * Fresh vegetables: 2 cups per 2.3 kg (5 lbs) displaces pellet meal * No highly digestible, energy-dense foods (e.g. beans, peas, grains, nuts, corn) \> dysbiosis, cecal blockage * Mixed ration/muesli-style pellets promote selective eating \> unbalanced * Unlimited fresh water * Dietary changes should be gradual

Answer 30

**Chapter 12 – Basic Approach to Veterinary Care of Rabbits** Joao Brandao, Jennifer Graham, Katherine Quesenberry **Housing** * Rubberized mats provide grip and fecal/urine drainage * Feed – good quality hay & pellets + leafy greens for anorectic rabbits * Fresh water should always be available – studies show rabbits prefer dishes so offer one regardless (if they like bottles, still give one too) * Hospitalized away from predators * Warm areas for reptiles or birds can cause hyperthermia **Handling & Restraint** * Rabbit skeleton is 7-8% of BW – other mammals typically 12-13% * 57% of rabbits struggle slightly when handles, 61-75% show signs of fear when handled by an unfamiliar person * Handling techniques * One hand on thorax or holding the scruff, the other supporting the hindlimbs * Fractious rabbits should be in the football hold (face in elbow, holding the hindlimbs) * Fractious rabbits should be placed rear end first to reduce injury * Towel burritos can be useful for examination or medication if an assistant is not available * Rabbits are obligate nasal breathers so don’t occlude the nostrils * Rabbits appear calmer on their backs – they go into a sort of tonic immobility with lower HR, RR, and corticosterone levels **Physical Examination** * Dyspneic rabbits should be placed in oxygen cage before examination (midazolam 0.5-1 mg/kg) is an effective calming sedative * Rectal temperature is a prognostic indicator – each 1C (1.8F) decrease in temp doubles the odds of death * Use a nonslip surface on the table to avoid injury * Sedation or anesthesia is likely necessary for a thorough evaluation of the oral cavity * A firm, dough-like or tympanic stomach; gas or fluid filled intestines, or absence of gut sounds may be present with stasis * Grimace scale has been established for rabbits – orbital tightening, cheek flattening, pointing of the nose, whisker changes are indicative of pain – should be used post-operatively **Sample Collection** * Blood collection * Lateral saphenous, cephalic, jugular, marginal ear veins, central auricular artery * Concern over sloughing ear in small eared breeds * Large jugular veins are difficult to access in females with a large dewlap. * Hematologic & Biochemical Testing * Veterinary BG monitors overestimate blood glucose * Severe hyperglycemia (\>360 mg/dL, \>20 mmol/L) is associated with a poor prognosis * Plasma sodium levels decrease with hyperglycemia * Lactate increase of 3.3 mmol/L within 48 hours of initial examination is associated with a better prognosis * Urine and Fecal Collection * Cystocentesis – US guidance to avoid the gut * Urethral catheterization – well lubricated 9-Fr catheter * Female – sternal recumbency, urethral opening on the floor of the vagina * Male – sitting position for extrusion of the penis – retrograde placement into the ejaculatory canal and vesicular gland can occur. In dorsal recumbency, the catheter is passed into the urethra and the other hand applies pressure over the pubic symphysis which will feel the advancing catheter and help direct it to the bladder * Dermatologic Sampling * Tape preps can help find Cheyletiella, bacteria, and yeast * Cerebrospinal Fluid Tap * Best site is the cerebellomedullary cistern * Position rabbit in lateral recumbency with head flexed toward the chest at a 90-degree angle * Shave the fur over the neck from the occipital protuberance to the third cervical vertebrae and past the wings of the atlas * Landmarks – cranial margins of the wings of the atlas and the occipital protuberance – place the needle midways between these points directly perpendicular to the skin * Collect fluid as it drips – attaching a syringe will likely cause blood contamination from the movement **Treatment Techniques** * Catheterization and Fluid Therapy * Cephalic, saphenous, or lateral ear vein – sloughing can result from fluids in the ear vein * Take care not to cause fluid overload – 50-70 mL/kg/day can be tolerated in nearly all patients with volumes up to 1.5-2 times maintenance in patients without cardiac disease * Normal fluid needs are 100-150 mL/kg/day * Intraosseous catheters can be placed in the proximal humerus, greater trochanter of the femur, or tibial crest in patients whose peripheral vessels are collapsed from dehydration * Fluids injected into the tibial marrow cavity reach the heart in 10 seconds * Apply antimicrobial ointment to the insertion site with a light dressing to hold the catheter in place * Gross & microscopic changes to the metaphyseal bone from the catheter resolve in 3 weeks * Subcutaneous fluids – 100-120 mL/kd/day divided into 2-3 treatments daily – decrease if edema is occurring * Injection Techniques * Same routes as other patients * If hindlimbs are used, inject in the cranial thigh muscles to avoid damaging the sciatic nerve in the caudal aspect of the leg * Avoid repeated injections of benzathine or procaine penicillin in the same location, as localized tissue reactions can occur * Oral Medications - Suspensions better than tablets * Enteral Feeding Support * Oxbow Critical Care, Emeraid Sustain Herbivore – timothy based formulas – fine grind can go through nasogastric tubes, Emeraid Intensive Care Herbivore is high-fiber cellulose and soy-protein for critical patients * Syringe feeding – if they take from a catheter tip syringe that is easiest; small or resistant patients can be fed with individual 1 mL syringes directly into the back of the oral cavity * Orogastric tubes can be used for a single feeding or to remove excess fluid from the stomach * Nasogastric tubes – measure from the tip of the nose to the last rib, 3.5-5 Fr used for most patients, place a drop of proparacaine in the nose, secure with a drop of cyanoacrylate glue on the furred area above the nose and tape or suture to the top of the head * Vaccinations – none in US, Europe – myxomatosis & rabbit viral hemorrhagic disease are recommended * Pain Control * Painful rabbits sit very still at back of the cage, hunched, grinding teeth. Other signs of pain include decreased fecal production, head elevation, aggression, isolation, and rapid breathing. Rabbit grimace scale is also useful. * Meloxicam 1 mg/kg PO q24h * Buprenorphine every 6-12 hours, fentanyl patches (25 mcg/hr in 4 kg rabbits) can be placed on the ear * Visceral pain may respond better to opioids (or lidocaine) and somatic or integumentary pain to NSAIDs * Anesthetic Delivery * Topical, injectable, inhalant, local * Topical anesthetic creams may take up to 45 minutes to become fully effective * Nasolacrimal cannulation * Ear cleaning * Minor cleaning can be done unsedated with cleaning solutions and cotton swabs * Severe otitis may require sedation, a flexible ear currette of CTAs to remove debris; ear can be flushed with a red rubber and warm saline (only if membrane isn’t ruptures)

Answer 31

**_Gastrointestinal Stasis Syndrome_**: common term to describe reduced/absent GI motility, one of the most common disorders * Often caused by inappropriate diet but can be initiated by stress (illness, painful condition, stressful event) * Eventually stop eating \> lack of food exacerbates GI stasis \> can be rapidly life-threatening * **_The Role of Fiber_**: large quantities of indigestible fiber are main driving force for normal intestinal motility * Fiber stimulates cecocolic motility (distension effect of bulk, or direct effect) * High fiber diets promote production of specific volatile fatty acids in cecum that promote peristalsis * Inadequate coarse fiber inhibits peristalsis * Hair is normally ingested while grooming but they cannot vomit accumulated hair \> normal GI motility moves hair along out w/ food into feces * Impaired GI motility results in accumulation of hair/ingesta in stomach \> fluid absorption from stomach compacts contents \> discomfort exacerbates anorexia \> GI hypomotility worsens * Results in large amounts of hair/compacted ingesta accumulated in stomach due to impaired intestinal motility (incorrect to call them “hairball,” “wool block,” “trichobezoar”) * **_The Effect of Diet and Cecocolic Motility_**: disrupted cecal microflora (dysbiosis) from inappropriate diet or GI stasis * Low fiber diet causes cecocolic hypomotility, prolongs retention of digesta in cecum, ultimately changes cecal microflora * Potentially pathogenic bacteria (*Clostridium, E. coli*) normally present in small numbers in cecum * Slowed cecocolic motility \> abnormal cecal fermentation products \> altered cecal pH \> increases pathogenic populations & decreases normal organisms \> pathologic changes (intestinal gas distension, death from enterotoxemia) * Gas, toxin \> pain, stress \> further hyporexia \> cycle of pain, inappetence, hypomotility * End-stage ileus can result w/o intervention * High fiber diets have low levels of carbohydrates \> decreased risk of enterotoxemia caused by carbohydrate overload of hindgut * Carbohydrates allow pathogens (*E. coli, Clostridium*) to proliferate * Glucose (byproduct of carbohydrate digestion) is necessary to produce iota toxin by *Clostridium* species * **_History and Clinical Signs_**: * Obtain complete dietary Hx (type/amount of pellets, hay, leafy greens, treats) * Primarily pelleted diet w/o adequate hay have increased risk of GI stasis * Higher risk if fed pellet mixes (dried fruits, vegetables, seeds, nuts, grains) * Acute GI stasis common after ingesting large volume of high-carbohydrate, high-fat treats * Low risk: fed unlimited good quality high-fiber grass/timothy hay, moderate fresh greens, minimal pellets, no/occasional treats * Stress alone (including stress from painful disease) can cause GI stasis * Changes in housing, introduction of new rabbits/pets, recent illnesses/trauma/surgery, underlying disease processes * Common: dental dz, chronic upper respiratory tract dz, neurological disorders, lower urinary tract dz, renal/hepatic disorders * Often have Hx of little/no exercise * Most common presenting complaint: gradual hyporexia over 2-7 days w/ subsequent decrease in fecal production \> will stop eating entirely if untreated * Water consumption often decreased * Feces are scant/dark/dry or absent * _+_ decreased activity due to abdominal pain * Pain: reluctant to move, less social, grind teeth, dig/scratch, hunched posture * **_Physical Examination Findings_**: * QAR w/ little/no lethargy * Palpate abdomen carefully (stomach contents, intestines, cecum) * Stomach contents vary w/ duration of disease but **always contains ingesta** (not fluid/case as in obstructed cases) * Fluid pulled from stomach results in firm/doughy feel that remains pitted on compression; occasionally very dehydrated/solid * Sometimes no fluid/gas palpable in stomach but intestines/cecum contain variable gas * Little/no feces in colon * Auscultate abdomen for borborygmus (intestinal hypomotility = absent/decreased GI sounds) * **_Diagnostic Testing_**: * CBC/CHEM: consistent w/ dehydration * Rads: useful to differentiate GI stasis from obstructive disorders, **stomach contains ingesta** that becomes compact/dense (may be surrounded by small halo of gas), moderate-severe gas distension of cecum, scant fecal pellets * **_Treatment_**: rehydrate patient & stomach contents, alleviate pain, provide nutrition, treat underlying disorders * Fluid therapy: IV, SC, PO * Mild stasis or treated early: respond well to PO/SC fluids on outpatient basis * Anorexic 1-2 days: usually severely dehydrated & require hospitalization for IVFT * Rehydrate stomach w/ assisted feeding _+_ placing NG tube * Ingestion of fibrous food critical to reestablish GI motility * Ensure patient eats during/after treatment (anorexia exacerbates GI hypomotility, deranges GI microflora, prevents secondary hepatic lipidosis) * Do not feed pineapple, pineapple juice, papaya \> ineffective/detrimental * GI stasis has moderate-severe gut pain \> opioids _+_ NSAID (if hydrated, no underlying renal disorder) * Lidocaine CRI useful for preventing pain & GI stasis * Start w/ parenteral route due to limited intestinal absorption w/ ileus * Intestinal prokinetic agents: metoclopramide initially parenterally, ranitidine, cisapride * Antibiotics only if severe dysbiosis * Encourage movement to stimulate gut motility further \> make rabbit hop around on floor 1-2X/day * Treat for 3-5 days, most will eat/defecate w/in 24-48 hours (initial feces may be abnormal, containing mucus/hair) * Other remedies that are not beneficial: lubricants (petroleum laxatives), protein-digesting enzymes (pineapple, papain; may increase risk of GI ulceration), simethicone (appears to have no ill effects)

Answer 32

**_Gastrointestinal Obstructive Disorders: Acute Gastrointestinal Obstruction and Moving Obstructions_** * Usually caused by compact mat or “felt” of hair approximately 3 x 1 cm (almond sized) \> may be compacted in cecum then ingested/swallowed whole w/ other cecal contents during normal cecotrophy * Other foreign objects: carpet, other cloth fibers, locust beans, plastic * Extraluminal compression: neoplasia, postsurgical adhesions, tapeworm cysts, abscesses, hernias * **Acute GI obstruction** (GI dilation or “bloat”): acute, life-threatening * Hypovolemic shock \> sudden loss of fluid into lumen of GIT proximal to obstruction * 200-250 mL accumulates in obstructed intestinal segment then stomach w/in hours \> fluid resorption impaired in obstructed segments \> rapid fluid loss \> hypovolemic shock * Gas formation proximal to obstruction \> GIT distension * Gut pH, bacterial flora shift \> Enterobacteriaceae, gas-formed clostridia increase GI distension * Stretched intestines compromises venous outflow \> pressure necrosis \> motility declines \> secondary GI stasis * _+_ Acute stomach rupture * Rapid course of disease depends on obstruction location * Most common: proximal duodenum (approx. 2-5 cm from pylorus where lumen narrows) * Shock w/in hours, death w/in 6-8 hours * Distal obstructions (jejunum, ileocecocolonic junction): intestinal loops progressively fill w/ fluid/gas over longer time (jejujum average death in 12-24 hours, ileum average death in 21 hours) * **Intestinal tract proximal to obstruction becomes** hypomotile \> often successful moving obstruction distally, there “**moving obstructions**” are common * Obstruction may pass w/ appropriate tx, or small mats of hair w/o tx * Cx resemble GI stasis * **_History and Physical Examination Findings_**: * **Sudden anorexia, depression**, _+_ acutely dead w/o premonitory signs (if acute proximal obstruction), refusing food, no fecal production * GI sounds may be audible from a distance w/ moving obstructions * Rabbit may stretch out & change positions frequently to get comfortable * _Complete obstruction_: severe pain (reluctance to move, hunched posture) * _Shock development_: severely depressed, listless, laterally recumbent, minimally responsive to external stimuli * _Stomach rupture_: suddenly cry out, death * Stomach palpates large, fluid-filled/tympanic, _+_ painful * Gut sounds increase before affected intestinal segments become necrotic, GI motility may be visible thru abdominal wall * Initially animals are alert but quiet, then w/ onset of shock becomes hypothermic, bradycardic, hypotensive * **Always obtain body temperature**, body temperature declines w/ shock * 98-99\*F in early stages of shock * \<98F is severe, life-threatening shock * **_Diagnostic Testing_**: * **RADS: stomach distended w/ fluid (not ingesta)** _+_ gas-distended GI loops * Proximal/duodenal or late-stage distal obstructions: severe stomach distension w/ fluid _+_ gas cap (**characteristic “fried egg” appearance**) * _CBC/CHEM_: glucose \>300 mg/dL (esp at onset of shock), increased renal values _+_ acute renal failure, r/o liver lobe torsion * **_Initial Medical Treatment_**: immediate warming (if hypothermic), treat shock, decompress stomach, correct fluid/electrolyte imbalances, control pain (opioids) * IVF (shock fluids) _+_ hypertonic saline/hetastarch * Avoid NSAIDs until renal status known * Sedation _+_ gas anesthesia necessary to decompress stomach \> oro-gastric tube (cuts hole at end of red-rubber catheter) measured from distance from nose to last rib \> pass tube while holding head in ventroflexion * **No percutaneous trochariazation of stomach \> likely ruptures stomach** * **Stomach fluid is prognostic** \> should be green/smell of food but if red/black then stomach likely necrotic w/ grave Px * Obstruction usually passes after medical tx & decompression \> rads/palpation to determine if obstruction is passing * Repeat decompression if needed, but surgery indicated if no improvement after second decompression (intestines will necrose if obstruction not relieved) * **_Surgical Treatment_**: exploratory laparotomy * Indications: lack of response to medical treatment, inability to decompress stomach, declining GIT motility \> indicates extraluminal obstruction or not moving * Always place ETT due to risk of intraoperative gastric reflux * Ideally decompress stomach & stabilize shock pre-operatively * IVF, heat support, lidocaine CRI (analgesia, anti-inflammatory, helps prevent postoperative ileus) * Most acute intraluminal obstructions are in proximal duodenum (3-5 cm from pylorus) \> avoid enterotomy, manipulate foreign body into cecum or move into stomach for gastrotomy * **Gastrotomies better tolerated than enterotomy** (lower post-operative complications: stricture, leakage, GI stasis) * Assess intestinal viability for potential intestinal resection & anastomosis * Grave Px if large sections of intestinal loops ischemic \> euthanize * If negative explore \> evaluate for evidence of neoplasia, abscesses, adhesions * Px: good if foreign body promptly removed, guarded to poor if intestinal viability is compromised

Answer 33

**_Cecotrophy and Intermittent Diarrhea_**: * Owners may confuse cecotrophs for diarrhea if cecotrophs not eaten (multiple soft fecal pellets stuck together resembling a blackberry) \> not consumed if physically unable to do so or if abnormally formed * Obesity, musculoskeletal disorders, vestibular dz, dental dz, pain, physical barriers (E-collars) * Abnormal cecal motility, pH, flora \> soft/malformed/pasty/odiferous cecotrophs not eaten * Commonly caused by dietary deficiencies * Stress, concurrent dz, Abx * Dx: Hx, rabbits produce normal fecal pellets throughout the day, soft feces found on fur or smeared on flooring * If rabbit unable to reach anus: feces pasted to perineum, secondary dermatitis * PE: obesity or signs of neuromuscular/dental/painful disorder * Tx: correct underlying disorder * If rabbit can physically reach anus, question owner about diet \> commonly insufficient fiber (hay) or excessive carbohydrates * Correction of diet usually corrects problem \> feed ONLY hay (preferably first-cut, high fiber) until uneaten cecotrophs no longer seen, then gradually add back pellets, then greens * (some rabbits always get abnormal cecotrophs with greens so need to have greens permanently withheld)

Answer 34

**_Cecoliths_**: abnormally hard lumps of cecal contents from compaction/dehydration of cecal/colonic material due to altered motility (cecum, colon) or abnormal diet (short fiber length, feeding indigestible fiber e.g. psyllium) * Chronic Hx of large/malformed feces, recurrent cecal impaction, abdominal pain, anorexia * PE: underweight & lacking normal muscle mass (since cannot form normal cecotrophs), _+_ gas accumulation in sacculated large intestine if completely obstructed (painful, moribund) * **Congenital progressive fatal disorder of sodium transport into cecum in homozygous spotted (English Spot) & Checkered Giant breeds \>** called “**megacolon-syndrome**” but involves cecum primarily * Presumptive Dx: palpation of doughy to very firm material in cecum; rads/AUS confirm presence of cecoliths * Tx: rehydration of inspissated cecal/colonic contents (IV/SC fluids, may need long term SC fluids), feed foods w/ high water content (feeding slurries, wetted leafy vegetables), appropriate fiber source (grass hay) to stimulate normal cecal motility/function, intestinal promotility agents, analgesia * Long term Px: guarded to poor * **Complete cecal obstipation** \> critically ill/painful, requires immediate tx (IVF, analgesia) * May be able to soften/move cecolith w/ gentle enema (careful: colon may be necrotic when obstructed) \> surgical removal once stable if medical therapy fails

Answer 35

**_Dysbiosis, Enteritis Complex, and Enterotoxemia_** * Enteritis complex common: range from soft stool, diarrhea, enterotoxemia, sepsis, death * Simple (soft/pasty stool as only Cx) can be due to minor disruption of cecal flora, pH, motility \> correct diet, add fiber (hay), decrease stress * Factors allowing pathogenic bacteria to proliferate: stress, diet, antibiotics, genetic predisposition to gut dysfunction * Epinephrine-mediated inhibition of gut motility believed to cause stress-induced enteritis **_Enterotoxemia_**: characterized by more significant than w/ enteritis, caused by **iota-like toxin from *Clostridium spiroforme*** * Mostly affects **newly weaned animals (3-6 weeks old)** \> highest mortality rate * Can be from simple exposure to *C. spiroforme* due to underdevelopment population of normal GI flora & high gastric pH that allows proliferation * Adults more resistant, usually need stress (dietary, environmental) to induce dysbiosis * Rapidly growing *C. spiroforme* significantly alters cecal flora * Nursing does develop “**milk enterotoxemia**” from *Clostridium* enterotoxin in doe’s cecum \> passed to bunnies in milk * Acute dz: anorexia, marked depression, brown/watery diarrhea soiling perineum/rear legs may contain blood/mucus * 24-48h: hypothermic, moribund, death * Nx: petechial/ecchymotic hemorrhages on serosal surface of cecum _+_ appendix/proximal colon * Various gas amounts throughout GIT, cecum, colon from ileus * _+_ Hemorrhage, pseudomembranes, mucus in mucosa of cecum/proximal colon **_Mucoid Enterititis_**: major cause of morbidity/death in 7-14 weeks old * **Cx: anorexia, lethargy, weight loss, diarrhea, cecal impaction, excessive mucus production by cecum** * Unknown cause – possible relation btwn bacterial dysbiosus, hyperacidity of cecum, & symptoms * Mucus production w/in cecum/colon stimulated by altered cecal pH (from changes in production/absorption of volatile fatty acids or vigorous fermentation of carbohydrates that destabilize cecal microbial population) * Prevention: feed diet high in fiber and low in simple carbohydrates **_Antibiotic-Induced Dysbiosis_**: clindamycin, lincomycin, ampicillin, amoxicillin, amoxicillin-clavulanic acid, cephalosporins, many penicillins, erythromycin \> suppress normal flora, allows pathogen proliferation \> enteritis **_Treatment and Prevention of Dysbiosis and Enterotoxemia_**: * Aggressive supportive care \> **correct dehydration, maintain normal hydration (IV/IO fluids),** assist feed * Antimicrobials have limited value, used primarily as support (e.g. *Clostridium spiroforme* sensitive to metronidazole/penicillin G \> may reduce deaths from enterotoxemia) * Efforts to increase cecal/colonic motility * Discourage growth of pathogenic bacteria & production of toxins * Cholestyramine (ion-exchange resin that binds bacterial toxins) may prevent death in clindamycin-induced enterotoxemia * Supporting growth of normal flora \> cecal transfaunation? * Prevention: optimal husbandry, minimize stress, feed good-quality grass hay, limit/remove pellets from diet * Pellets should have no less than 18-20% fiber, limit to \<1/3 cup per 5 lbs * Avoid sudden dietary changes * Make hay available to weanlings from 3 weeks of age, avoid early/forced weaning **_Primary Bacterial Enteritis_**: * Occasionally seen in adult pet rabbits * Common mortality in commercial rabbit industry (mortality 50-100%) * Typical enteritis in neonates or \<16 weeks stressed by weaning/transport/overcrowding * Enterohemorrhagic **_Escherichia coli_** (potentially zoonotic): * Shiga toxins cause hemorrhagic colitis w/ hemorrhagic diarrhea * Susceptible via oral ingestion \> develop **thrombotic microangiopathy** (hallmark of shiga toxin) which is believed to cause acute renal failure * 7 groups of pathogenic *E.* coli; enteropathogenic *E. coli* causes major economic loss in commercial rabbit industry * Attaching & effacing *E. coli* strain where bacterial adherence (via fimbrial adhesin) results in destruction of brush boarder & rearrangement of enterocyte structure * Diarrhea from villus atrophy, malabsorption \> severity varies based on age, specific serogroup * Infected does pass passive immunity to litters * Disease limited to cecum/colon \> cecal wall inflamed w/ longitudinal “paintbrush hemorrhages * Severe cases: intussusception, rectal prolapse * Presumptive Dx: isolation of *E. coli* strains from stool/tissue samples from affected animals (however, nonpathogenic *E. coli* can proliferate in any rabbit w/ dysbiosis) * Definitive Dx: histology of tissues observing *E. coli* attachment to intestinal cells * (Serotyping *E. coli* available for research purposes only) * Tx: antibiotics (guided by C&S), supportive care (fluids, feeding, maintain normothermia) * Prior to culture results, use TMS or enrofloxacin **_Proliferative Enteritis, Proliferative Enteropathy, Proliferate Enterocolitis_**: *Lawsonia intracellularis* * Causes enterocolitis as both single pathogen & in associated w/ enteropathogenic strain of *E. coli* (distinct from prototypical rabbit diarrhea *E. coli* strain) * Gram-negative, curved to spiral shaped, found free in apical cytoplasm of intestinal epithelial cells * Cx: acute diarrheal disease in age 2-4 mo (weanlings) * Histo: **proliferative ileitis w/ or w/o proliferative colitis characterized by epithelial hyperplasia, mucosal inflammation** * Tx: chloramphenicol, florfenicol **_Tyzzer’s Disease_**: *Clostridium piliforme* (formerly *Bacillus piliformes*) * Motile gram-variable, spore-forming, obligate intracellular bacterium * Stress (overcrowding, unsanitary conditions, high temps, breeding) plays important role * Cx: watery diarrhea, depression, death * Morbidity/mortality rates high in weanlings, older rabbits develop chronic form (= chronic weight loss) * Nx: **characteristic foci of necrosis in mucosa of proximal colon** * Tx: palliative once Cx develop * Exposed animals tx w/ preventative measures (isolation, good hygiene, supportive care, high-fiber diet) may not develop dz * Prevention: good husbandry * Disinfection: 0.3% sodium hypochlorite, heating to 173F for 30 min **_Other Causes of Bacterial Enteritis_** * Campylobacter species (*C. cuniculorum, C. jejuni, C. coli*) found in health/diarrheic rabbits * *C. cuniculorum* has antibiotic resistance to fluorquinolones, macrolides but sensitive to chloramphenicol (pathogenic role unknown) * Water-borne pathogens: *Salmonella* spp, *Klebsiella pneumonia, Klebsiella oxytoca, Pseudomonas aeruginosa* * Outbreaks when food/water system is contaminated * Salmonellosis uncommon but causes disease w/ high morbitidy/mortality \> most commonly ***Salmonella typhimurium*** but other species/serovars reported * Cx: sepsis \> quick death; _+_ diarrhea * Nx: consistent w/ septicemia, vascular congestion of organs, diffusely distributed petechial hemorrhages, LN/GALT edematous w/ necrotic foci * Mycobacteriosis (*Mycobacterium bovis, Mycobacterium avium* subsp *paratuberculosis*): diarrhea, emaciation * *M. bovis* is zoonotic, *M. a. paratuberculosis* has zoonotic capacity * Natural infections of *M. a. paratuberculosis* reported in wild rabbits from farms w/ high prevalence of ruminant paratuberculosis * Supportive Dx: fecal cytology, tissue bx confirming acid-fast bacteria * Definitive Dx: mycobacterial culture, PCR * Tx: challenging, controversial

Answer 36

**_Viral Disease of the Digestive Tract_** **_Papillomatosis_**: benign, caused by papillomavirus, only reported in lab rabbits (esp NZW) * Cx: small white growths on ventral surface of tongue, rarely elsewhere in mouth * Early lesions are sessile \> becomes rugose/pedunculated \> ultimately ulcerated * Papillomas can be \>4-5mm diameter but typically smaller (1-3 mm) * Can persist for up to 145 days but often disappear w/in weeks **_Rabbit Hemorrhagic Disease Virus_**: *Lagovirus* genus w/in family Caliciviridae include rabbit hemorrhagic disease virus (RHDV), European brown hare syndrome virus, nonpathogenic rabbit calicivirus * European brown hare syndrome affects European hares of *Lepus* genus * RHDV specifically affects domestic rabbits; no disease in wild cottontail rabbits, jackrabbits, hares * Endemic in Europe, Cuba, Australia, New Zealand * Limited outbreaks in Middle East, South America, Mexico (eradicated), USA (sporadic outbreaks, last in Indiana in 2005) * 2010: **new variant (hemorrhagic disease virus 2 [RHDV2])** ID’d in Europe \> reported in UK, Australia since 2015 * **Affects both domestic/wild rabbits**; disease in rabbits vaccinated against classic RHDV strain * Clinical dz in rabbits \>2 mo (younger unaffected) * Virus shed in urine, feces, respiratory secretions * Transmission: direct contact, contact w/ carcasses/fur from affected rabbits, fomites (water/feed/utensils/clothing/cages), vectors (flies, insects), feces from predators eating infected rabbits * Highly infections, high morbidity (40-100%) & mortality (~100%); higher M&M in naive populations * Incubation period: 1-3 days * Outbreaks: # rabbits infected peaks in 2-3 days, disease course lasts 7-13 days * **RHDV2 variant is less virulent w/ lower M&M, clinical signs more chronic** * Virus replicates in liver \> severe hepatic necrosis/death from DIC * Peracute dz: death w/o premonitory signs, or febrile/lethargic & die w/in 12-36 h * Acute dz: febrile, depressed, lethargic, anorexic, constipated/diarrhea, _+_ neurologic (ataxia, opisthotonos, excitement, seizures) * End-stage dz: tachypnea, cyanosis, blood-tinged foamy nasal discharge * Some have slower dz course: jaundice, depression, anorexia, fever, death w/in 1-2 weeks * Subacute dz: milder Cx, rabbits often live * Asymptomatic rabbits can have persistent/latent infections * CBC: lymphopenia, gradual thrombocytopenia * Prolonged PT/PTT in moribund rabbits w/ detectable fibrin degradation products * Nx: **hepatic necrosis, splenomegaly, evidence of DIC**, congestion/hemorrhage in most organs (most pronounced in lungs), pale liver, periportal necrosis w/ fine reticular pattern, spleen dark/thickened, catarrhal enteritis * Presumptive Dx: Hx, Cx, pathologic findings \> **contact state/federal regulatory agencies if disease suspected (reportable), only send samples to diagnostic labs under secure conditions** * Definitive Dx: ID virus (EM, RT-PCR, Western blot, ELISA) * Vaccines: * Heat-killed liver extracts, VP60 protein, recombinant myxoma-RHD live virus \> no protection against RHDV2 * Specific RHDV-2 vaccines or combined RHDV-1/RHDV-2 vaccines commercially available in Europe/UK * **Disinfection: inactivate virus w/ 0.5% sodium hypochlorite or 1% formalin** **_Rabbit Enteric Coronavirus_**: affects 3-10 week old rabbits, also found in clinically normal adults * Cx of naturally occurring outbreaks: lethargy, diarrhea, abdominal swelling, death * Pleural effusion, cardiomyopathy also associated w/ coronavirus-like particles * High morbidity/mortality (e.g. one outbreak had 40-60% affected rabbits w/ 100% dead w/in 24h) * Nx: fluid cecal contents, atrophy of intestinal villi * Tentative Dx: Hx, Cx, Nx, histopathology * Hemagglutination activity in feces is supportive * Confirm Dx by demonstrating virus in feces/cecal contents **_Rotavirus_**: endemic w/in domestic rabbits, wild *Sylvilagus, Lepus* lagomorphs (Europe, Asia, USA) * Infants most susceptible \> virus targets terminally differentiated enterocytes lining tips of villi of jejunum/ileum * Less severe/subclinical infections in weaned rabbits due to protective maternal antibodies (some protection past 45 days when antibody levels decline) * Morbidity/mortality varies w/ age, host immunity, environmental stressors * Increased w/ coinfection (e.g. *E. coli*) * Cx: diarrhea, dehydration, sudden death * Nx: mild-severe villus blunting, villus fusion, submucosal edema of SI, fluid cecal contents, lamina propria infiltrated w/ lymphocytes _+_ heterophils * Definitive Dx: histopathology of intestine * Suggestive Dx: virus isolation, demonstration of antibodies (detectable w/ human ELISA test kits for rotavirus group A) * Prevention/control complicated (highly infectious): reduce stress (reduce crowding, stop breeding, remove socially dominant animals, add dietary fiber), improve hygiene, & appropriate tx concurrent dz **_Other Viral Causes of Enteritis_** * Adenovirus, astroviruses in young rabbits w/ diarrhea/enteritis * Co-pathogens common * Same prevention/control as rotavirus * Novel bocaparvovirus (parvovirus) described in both healthy rabbits & rabbits w/ enteritis \> prevalence, pathogenesis unknown

Answer 37

**_Parasitic Disorders of the Gastrointestinal Tract_** **_Coccidia_**: most common parasites of GIT, frequent cause of illness \<6 mo * Adults rarely clinically ill \> oocytes on fecal exam does not mean disease * 12 species of genus *Eimeria* infect rabbits, only 1 species (*Eimeria stiedae*) is found outside GIT (liver) * Diseased rabbits often have 2+ coccidia species * **_Hepatic Coccidia_**: ***Eimeria stiedae*** is ubiquitous in open rabbitries not treating preventatively w/ coccidiostats * Infective sporulated oocysts ingested \> excystation in duodenum \> sporozoites penetrate intestinal mucosal to go to bile epithelial cells \> schizogony \> merozoites invade contiguous epithelial cells \> gametogeny \> microgametes \> macrogametes \> develops into oocyst \> oocysts rupture from epithelial cells \> passed in bile through feces * Many infections asymptomatic, but can be fatal (esp. young rabbits) * Cx (heavily infected): signs related to decreased hepatic function & bile duct obstruction (anorexia, debilitation; diarrhea/constipation in terminal stages), _+_ abdominal enlargement, _+_ icteric * CHEM: increased ALT, AST, bile acids, tbili * RADS: _+_ hepatomegaly, _+_ ascites * Nx: hepatomegaly w/ yellowish-white, nodular, abscess-like lesions of varying sizes (some w/in fibrous capsule) * Dx: ID oocysts in sample sample, biopsy, or fecal * **_Intestinal Coccidia_**: * Important species: *Eimeria perforans, Eimeria magna, Eimeria media, Eimeria irresidua* **(*E. perforans* most common)** * Ingestion of sporulated oocysts (cecotrophs eaten from anus do not contain infectious oocysts) * Cx: varies based on age, organism, parasitic burden, susceptibility of animal * Subclinical infection common in young/adults \> finding oocysts in clinically normal rabbit does not warrant tx * Cx often associated w/ poor husbandry, overcrowding, generally \<6 mo (or severely immunosuppressed older rabbits) * Mild intermittent to severe diarrhea (may have mucus/blood), weight loss, dehydration * Intussusception may develop w/ diarrhea * Death from dehydration, secondary intestinal dysbiosus * Nx: lesions in SI/LI (depends on organism), _+_ ulcerated intestinal epithelium * Presumptive Dx supported by organism in fecal samples or intestinal scrapings in symptomatic animals * Definitive diagnosis based on histologic findings * Tx: goal is to limit multiplication until immunity develops; survivors develop lifelong immunity * Groups of rabbits: sulfadimethoxine, amprolium * Individuals: toltrazuril, sulfadimethoxine, TMS * Prevention: good husbandry, clean stress-free environments **_Cryptosporidia_** (*Cryptosporidia parvum*, no effective treatment) * Causes discrete/transitory diarrhea in young rabbits (peaks at 30-40 days), may lead to growth retardation * Adult rabbits unaffected * Cx: diarrhea lasting 3-5 days, hyporexia, depression, lethargy, exhaustion, dehydration * Pathogenesis: infects intestinal tract (esp. ileum, jejunum) * Bx: atrophy of villi in ileum in young rabbits **_Other Protozoa_**: nonpathogenic flagellates found in feces, more commonly w/ diarrhea * Anterior SI: *Giardia duodenalis* * Cecum: *Monocercomonas cuniculi, Retortamonas cuniculi*, large cilated protozoa (genus *Isotricha* found in ruminants) * Cecum/colon: *Entamoeba cuniculi* **_Helminths_** * **_Nematodes_**: * ***Passalurus ambiguus***: common pinworm of domestic rabbits (also reported: *Passalurus nonanulatus*) * **Nonpathogenic** (even in large numbers) * Adult pinworm in anterior portion of cecum/colon, grossly visible in lumen of cecum/large intestine & when passed w/ fresh feces * Juvenile stages in mucosa of SI/cecum * Direct lifecycle: ingestion of infective eggs during cecotrophy * Commonly seen during routine surgical produces (e.g. OVH) * Dx: ID adult worms or demonstration of eggs in feces * Tx (usually insisted by owners): benzimidazoles (thiabendazole, fenbendazole), piperazine * Other helminths rare * Reported in farmed rabbits: *Obeliscoides cuniculi, Graphidium strigosum, P. ambiguus, Trichuris leporis, Trichostrongylus spp., Strongyloides spp.* * **_Cestodes and Trematodes_**: clinical disease not reported in pet rabbits, only in wild/lab populations * Several spp cestodes can be hosted by GIT: *Cittotaeniae variabilis, Mosgovoyia pectinate americana, Mosgovoyia perplexa, Monoecocestus americana, Ctenotaenia ctenoides* * Life cycle unknown; oribatid mites or ants may be intermediary hosts? * Rabbits are intermediate hosts for several dog/fox tapeworms: *Cysticercus pisiformes,* larval stage of *Taenia pisiformis*, *Coenurus serialis*, larval stage of *Taenia serialis*, *Echinococcus granulosus* * Oral ingestion of eggs (from carnivore feces) \> larval migration from intestine \> cysts in various tissues * Tx: single dose praziquantel * Prevention: avoid feeding wet grass clippings from areas where possible natural hosts may be present

Answer 38

**_Neoplasia_** * _Uncommon_: * Stomach: adenocarcinoma * Intestines: leiomyoma, leiomyosarcoma * Sacculus rotundus: papilloma * Rectal squamous columnar junction: papilloma * Metastatic neoplasia (most common: uterine adenocarcinoma) involving GIT * Tx: surgical resection (can resect intestinal masses if detected early) * _Rectal papillomas_ (cauliflower-like, fungating masses from anorectal junction): benign, unrelated to papillomas of skin/oral cavity * Tx: removal * _Bile duct: adenoma, adenocarcinoma_ * Multiple tumors consisting of interlocking cysts filled w/ thick, viscous myxoid fluid * Possible causative factors: noxious stimuli (infection w/ *E. stiedae*?) * Dx: radiography, AUS * Tx: none (surgery not practical) * Px: grave (metastatic disease often military) **_Liver Lobe Torsion_**: acute vs. chronic forms * **Caudate lobe** most affected (also reported: right lobe, quadrate lobe, posterior lobule of the left hepatic lobe) * _Acute LLT_: rapid progression, deteriorate over a short time (obtunded, hypothemic) * Hx: acute GI obstruction (acute anorexia, cranial abdominal discomfort, weak/depressed) * PE: stomach has food/small volume gas suggestive of GI stasis syndrome, _+_ abnormal liver palpable, _+_ pale MM (if hemoabdomen present) * Death w/in 12-72h from onset of signs * CBC/CHEM: anemia (PCV 16-17%), mild-severe increases in liver enzymes (ALT, AST, GGT) although may be normal initially * RADS: rounded liver margins, hepatomegaly, increased liver density, _+_ ascites * **AUS is diagnostic**, may demonstrate heterogenous appearance & lack of color doppler blood flow in affected liver lobe * _+_ Hemoabdomen: free fluid in peritoneum, fresh blood on abdominocentesis * Tx: initial supportive care (IVF, analgesia, thermal support), **prompt liver lobectomy is treatment of choice** but some will survive on supportive care alone * _Chronic LLT_: **nonspecific signs, “poor doers” w/ hx recurrent GI stasis** * LLT has been Dx at Nx in previously asymptomatic rabbits * PE: _+_ firm, nonpainful mass in cranial abdomen * CBC/CHEM: _+_ mild-moderate increases in liver enzymes, _+_ anemia, _+_ azotemia * Dx: AUS of affected lobe * Tx: liver lobectomy **_Alfatoxicosis_** (from *Aspergillus flavus, Aspergillus parasiticus)* * LD50 in rabbits is one of the lowest of any species studied * Cx (from 1 outbreak): anorexia, dullness, weight loss then jaundice in terminal stages, death w/in 3-4d * Nx: livers congested/icteric, gallbladders distended w/ inspissated bile * Liver: degenerative changes of hepatic cells, dilatation/engorgement of sinusoids * Bile ducts: mild-severe periportal fibrosis * Dx: aflatoxin B1 levels in tested feed (90-540 mg/kg in this case) * Tx: remove contaminated feed, supportive care \> gradual disappearance of Cx, deaths

Answer 39

**Chapter 15 – Respiratory Disease** Angela Lennox, Elisabetta Mancinelli **Anatomy of the Respiratory Tract** * Rabbits are obligate nasal breathers – the epiglottis engages over the caudal margins of the soft palate – open mouth breathing indicates a severe abnormality * The chonchomaxillary cavity connects with the nasal cavity with a single slitlike opening on both sides making the space vulnerable to pathology * The nasolacrimal duct is closely associated with the nasal cavities, and bends ventromedially through the infratrochelar incisure through the nasolacrimal canal and ends on the dorsomedial side of the naris * Nasal cavities are also closely connected to the tympanic bulla – through the nasopharyngeal meatus and eustachian tubes * Dental disease can impact the paranasal sinuses, nasal cavity, nasolacrimal duct – disease of the nasal cavity can cause disease of the bullae * Epiglottis naturally sits above the soft palate – hyperextension of the head causes it to disengage * Each lung is divided into cranial, middle, caudal lobes (right has an accessory lobe) – there are no septa between lobules so pneumonia is typically generalized rather than localized **Physical Examination** * Signs of disease include nasal and ocular discharge, nasal flaring when breathing, increased effort and rate worsening with exertion * Rabbits with discharge may use their forefeet to clean it off, resulting in debris on the medial aspect of the feet * Rabbits with tracheitis will cough when trachea is palpated * Severe upper respiratory disease tends to increase inspiratory effort – lower respiratory disease tends to increase expiratory effort **Diagnostic Testing** * Laboratory analysis * Hematology may not show a leukocytosis, but an inverse shift in heterophill/lymphocyte ratio (2:3) may be suggestive * Culture & sensitivity are useful from deep nasal swabs, BAL, or nasolacrimal flushes * Diagnostic Imaging * Skull rads – five views – lateral, VD/DV, RLO, LRO, rostrocaudal * Thorax – three views * US – cardiac size and function, thoracic masses * CT – best for skull imaging * Sedation may be necessary for imaging in distressed or fractious patients – Midazolam 0.25 mg/kg, butorphanol 0.2 mg/kg * Endoscopy * 1.9 mm rigid scope can be place in patients weighing more than 2 kg **Diseases of the Upper Respiratory Tract** * Infectious Diseases * Bacterial Pathogens * Most common – P multocida (55%), B. bronchiseptica (52%), Pseudomonas (28%), Staphylococcus (17%) * Moraxella and E. coli isolated in other studies as well * Pasteurella * Strains vary in pathogenicity – can be transmitted hematogenously causing sepsis * Does with venereal infections can pass it vertically * Typically passed through the nose, spreads to all of respiratory tract * Risk factors – stress of concurrent disease, exposure to ammonia (poor husbandry), corticosteroids * Bordetella * Common inhabitant – usually only causes issues following another pathogen, usually Pasteurella * Pathogenic to guinea pigs, dogs, cats, and pigs * Staphylococcus – commonly isolated from nares, also a secondary pathogen * Viral Pathogens * Myxoma virus – can induce ocular and nasal discharge and dyspnea, also associated with acute hemorrhagic pneumonia * Herpes outbreaks have also been associated with respiratory signs * Noninfectious Diseases * Trauma * Inflammation of the glottis and stenosis of the trachea commonly reported * Has been corrected with ballooning stent placement * Dental Disease – produces nasal cavity disease which * Neoplasia – nasal mucosal adenocarcinoma reported * Miscellaneuos – single case of laryngeal paralysis reported **Diseases of the Lower Respiratory Tract** * Bacteria isolated from pulmonary lesions in order of frequency: Pasteurella, Bordetella, Psdeudomonas. Chlamydia has been isolated and Pneumocystis oryctogai has been isolated from newly weaned rabbits. * Myxoma virus is associated with acute hemorrhagic pneumonia * Neoplasia – Metastasis (uterine adenocarcinoma, osteosarcoma, lypmphoma, mammary carcinoma) **Diseases Producing Secondary Respiratory Syndromes** * Cardiomyopathy, endocardiosis, congestive heart failure * Diaphragmatic hernia – entrapment of stomach, intestines, fat, kidney * Pneumothorax from trauma * Thymoma **Treatment of Respiratory Disease** * Thoracocentesis – should be done with US guidance following preoxygenation and sedation – insert needle at 5^th-7^th or 2^nd-3^rd intercostal spaces, avoiding the heart * Antibiotic Therapy * Marbofloxacin effective against the majority of isolates in one study, except for Bordetella * Enrofloxacin, ciprofloxacin, and penicillin IV shown to also be effective against Pasteurella * Remember risk of enteric dysbiosis * Nebulization may be more appropriate in severe cashes * Can also instill antibiotics into the nasolacrimal duct * Rhinotomy * Three sided osteotomy technique (top, bottom, one side) us used to gain access to nasal fossae bilaterally while leaving a bone flap for closure * Nasal cavity can be flushed and debrided through that Prevention * Quarantine of new animals, proper husbandry, etc * Pasteurella free rabbits are available for laboratory use but are unlikely to be available as pets

Answer 40

**Chapter 16 – Disorders of the Urinary and Reproductive Systems** Nicola Di Girolamo, Paolo Selleri **Disorders of the Reproductive System** * Reproductive Physiology * Rabbits reach sexual maturity by 4-6 months of age * Induced ovulators * Serial cycles that last 7-14 days until conception * Receptivity is accompanied by swelling and congestion of the vulva (this is not vulvitis) * Bucks are precocious and may attempt to breed as early as 3 months * Spraying is a normal sexual behavior of intact bucks and some does – not a UTI * Common abnormalities in wild European hares – cystic endometrial hyperplasia, hydrosalpinx, extrauterine fetuses, neoplasms, psudopregnancies, resorptions * Female Disorders * Uterine Adenocarcinoma * Most common neoplasm of female rabbits * Age and breed are important risk factors (tan, French silver, Havana, Dutch \> 4 years old) – 50-70% prevalence * Invasion through the myometrium occurs early leading to hematogenous metastasis * Clinical signs * First clinical sign is hematuria or serosanguinous vaginal discharge (only 17% present this way) * Cystic mammary glands often develop conccurently * Diagnosis – enlarged uterus, uterine nodular masses * DDx – pregnancy, pyometra, metritis, hydrometra, endometrial venous aneurysms, endometrial hyperplasia * IHC shows there are two classes * Papillary adenocarcinomas are mostly (81%) receptor negative for both estrogen and progesterone * Tubular/solid adenocarcinomas are mostly positive for both receptors * So there may be more than one pathogenesis * US more sensitive than rads * Treatment – ovariohysterectomy is curative if the tumor is contained within the uterus, with survival times up to 22 months * Most metastatic disease is not macroscopically apparent. Rabbits should be rechecked every 3-6 months for 1-2 years following surgery to look for mets * Prevention * Ideal age is not determined (cancer has occurred as young as 2 years) * Spaying at 8-12 months is easiest with distensible ligaments and not as much fat * Endometrial Hyperplasia or Uterine Polyps * Endometrial changes exist along a continuum – polyps to cystic hyperplasia to adenomatous hyperplasia to adenocarcinoma * Deslorelin (4.7 mg) does not prevent the development of endometrial hyperplasia * US is the best diagnosis, treatment is OVH * Pyometra and Endometritis * CS – vaginal discharge, lethargy, weakness, enlarged abdomen * Recent history of parturition, pseudocyesis, or inability to breed * Can still occur in nulliparous does and can be secondary to adenocarcinoma * Common pathogens – Pasteurella & Staphylococcus are the most commonly isolated * Others – Chlamydia, Listeria, Moraxella, Actinomyces, Brucella melitensis, Salmonella * Diagnosis – palpation, US, rads, CBC may show mild leukocytosis and heterophilia or renal value elevation * Treatment – OVH likely necessary to remove exudates, give preoperative antibiotics * Hydrometra * CS – enlarged, fluid filled uterus, Tx with OVH * Uterine Torsion * Associated with pregnancy, hydrometra, endometritis * CS – shock, cachexia, abdominal distension * Grave prognosis * Congenital Abnormalities * Uterus unicornis – two ovaries, one uterus * Uterine atresia * Endometrial Venous Aneurysms * Cylindrical blood clots passed with the urine are highly suggestive * Affected does at high risk for fatal exsanguination * OVH is treatment of choice * Pseudopregnancy aka pseudocyesis * Typically lasts 16-17 days, followed by hair pulling and nesting behavior * CL secretes progesterone causing uterine and mammary development – most pronounce the first 10 days * Lower kindling rate in group housed does with one buck rather than those housed with a buck individually * Dystocia and Retained Fetuses * Gestation averages 31-32 days (28-36 days is range) and delivery is typically complete within 30 minutes * Litters range from 4-12 kits, both anterior and posterior presentations are normal * Risk factors – obesity, large fetuses, small pelvic canal, uterine inertia * CS – persistent contractions, straining, bloody or greenish brown discharge * Tx – Calcium followed by oxytocin (1-3 units) * C-section if no response * Prognosis is guarded * Pregnancy Toxemia * Last week of gestation – fetuses develop rapidly in second half of pregnancy * Risk factors – obesity and inadequate caloric intake * CS – weakness, depression, incoordination, anorexia, abortion, convulsions, coma * Clin Path – acidic urine (5-6 pH), proteinuria, ketonuria, hyperkalemia, ketonemia, hyperphosphatemia, hypocalcemia * Tx – calcium gluconate, feed once stabilized * Abdominal Pregnancy * Usually the fetuses mummify and are not an issue * Abortion and Resorption * Fetal death before 21 days results in resorption, after results in abortion * When reported, check doe for additional fetuses * Causes – infection, stress, genetics, trauma, drug effects, dietary imbalances, Listeria, herpes * Can be induced with aglepristone 10 mg/kg on days 15-16 after mating * Reduced Fertility * Malnutrition (ADE), heat stress, systemic illness, nitrate contamination, environmental distrubaances, endometrial adenocarcinoma, metritis, pyometra; old age, too young * Vitamin E deficiency – myodystrophy leads to abortions stillbirths and neonatal deaths * Hypervitaminosis A – fetal resorptions * Hypovitaminosis A – hydrocephaly * Uterine & Vaginal Prolapses – resolved by pulling uterus into abdomen and then performing an OVH * Male Disorders * Cyptorchidism * Testicles usually descended by 12 weeks of age * Scrotal sac does not develop if they don’t descend * Wait several weeks before surgery in case estimated age is wrong * Orchitis and Epididymitis * CS – fever, intermittent appetite, weight loss, testicles may be enlarged with obvious abscesses * Tx – castration, antibiotics * Paseurella is most commonly isolates – you should also request Treponema testing * Testicular Neoplasms * Uncommon, but seminomas, interstitial cell tumors, Sertoli cell tumors, teratoms, and hamartomas have been reported * Venereal Spirochetosis * Treponema paraluiscuniculi * Bucks can spread to several does and young can be affected * Disease is self-limiting and asymptomatic carriers occur until they are stressed * Lesions first appear on the perineum and genitalia and start as erythema progressing to edema, vesicles, ulcerations, and scab * Autoinfection causes the lesions to spread to chin, lips, nostrils, and eyelids * Diagnosis – usually by presentation, but you can submit a biopsy and request silver staining * Bucks are often asymptomatic carriers (may have star shaped scars on scrotum) * Females with multiple litters are likely to be positive * Treatment – penicillin G SC – 42-84,000 IU/kG q7d x 3 injections or 40-60,000 IU/kg IM q24h for 5-7 days **Disorders of the Mammary Glands** * Septic Mastitis * Mastitis can occur with lactation or in pseudopregnancy * Abscess can develop regardless of lactation status * Risk factors – heavy lactation, poor sanitation, abrasive bedding or carpeting, injury to teat * Clinical signs – depression, fever, anorexia, PUPUD, septicemia, death of doe or young; mammary glands are firm hot, and swollen and skin is discolored red to dark blue * Common isolates – Staphylococcus, Streptococcus, and Pasteurella – S. aureus mastitis is severe and can lead to septicemia in both doe and young * Dx – culture exudate from gland * Tx – enrofloxacin or TMS with fluids and pain management * Cross foster (risk of transmission to new doe) or bottle raise babies * Cystic Mastitis, Mammary Dysplasia, Mammary Tumors * Cystic mastitis occurs in both breeding and nonbreeding does * Glands are swollen and firm, with clear to serosanginous discharge when expressed * Not overtly painful * Associated with uterine hyperplasia and adenocarcinoma * Can lead to malignant changes leading to mammary adenocarcinoma and metastasis * Treatment is OVH and mastectomy if neoplastic

Answer 41

**Disorders of the Urinary System** * Intro * Presenting complaints – incontinence, inappropriate elimination, urine scalding, hematuria, stranguria, pollakuria * 1**0% of rabbits presenting to a teaching hospital were diagnosed with urinary tract diseas**e * Creatinine is a more reliable test of renal function than BUN * Urinalysis * Ideally urine is collected via cysto – use US and don’t hit the gut * Normal urine volume is 130 mL/kg/day * Urine is the primary excretion route for calcium and magnesium * First urine is the best to assess * Glucosuria can occur with stress * Normal pH is basic 7.7-9.6 * Specific gravity is between 1.007-1.051 * Triple phosphate and calcium carbonate crystals are common * **In a histo study, 33% died or were euthanized because of kidney disease; 25% of healthy rabbits had renal lesions** * **Renal abscesses, staphylococcal nephritis, pyelonephritis, and pyelitis were most common in rabbits \<5 months** * **Renal fibrosis with or without dystrophic calcification was most common in rabbits \>10 months** * Spontaneous amyloidosis was also observed * Urolithiasis & Hypercalciuria * Cystic, urethral, renal, and ureretal calculi all reported * Hypercalciuria commonly seen – sand or sludge in bladder * Rabbits maximize dietary calcium absorption – 45-60% of calcium is excreted in urine (other mammals is \<2%) * Phosphorus is excreted in the feces * History of limited exercise, free choice pellets, high calcium greens, alfalfa hay, or obese; vitamin or mineral supplementation * Clinical signs – depression, anorexia, weight loss, lethargy, hematuria, anuria, stranguria, grinding of teeth * Enlarged kidneys may be present with hydroureter or hydronephrosis * Some sand in bladder on rads can be incident * If renal calculi are present, GFR studies should be done (pyelography or renal scintigraphy) * **Pseudomonas and E coli may cause cystitis** * Uroliths in urethra may be removed or dislodged by catheterization * Using a surgical spoon in cystotomy is preferred to prevent pushing things into the urethra with flushing * If sand is present (not a calculus), give fluids and manually express the bladder – sedation can help relax the urethra for better success * Nephrotomy has been performed; nephrectomy not recommended * Change diet * Rabbits only need 0.22 g of calcium per 100 grams of food for optimal growth; alfalfa based pellets have 0.9-1.6 g/100g * Renal Failure * Acute – sudden disruption of filtration, accumulation of uremic toxins, dysregulation of fluid, electrolytes and acid-base; potentially reversible if identified and treated aggressively * Chronic – history of weight loss, anemia, PUPD, isosthenuria; kidneys palpate small and irregular * **Pyelonephritis – Pasteurella or Staph most commonly** * **Encephalitizoon causes subclinical, chronic, interstitial nephritis** * Hypercalcemia, renal calcinosis, interstitial fibrosis may result from hypervitaminosis D * Lymphoma commonly involves the kidneys * Treatment * Acute – correct perfusion, rehydrate, diurese – measure output volume (should be 5-10 mL/kg/hr during diuresis, 2 mL/kg/hr normally) * Chronic – long term SC fluid support * Hypervitaminosis D * Pathologic changes with mineral deposition in the aorta and kidneys will be the first things noticed on imaging * Nephrotoxicity * Aminoglycosides – give SC fluids concurrently * Tiletamine in Telazol – irreversible nephrosis at high doses, even low doses cause disease * Diclofenac * Other NSAIDS with chronic use as well * Renal Cysts – usually asymptomatic, polycystic kidney disease documented in New Zealand Whites * Encephalitozoonosis * Absorbed in intestines by mononuclear cells and distributed systemically * Spores have a predilection for kidneys, brain, and spinal tissue – appear in kidney after 31 days and in urine for up to 3 months * Infections typically cause nonsuppurative, granulomatous nephritis that can progress to interstitial fibrosis – but is usually chronic and subclinical * Incontinence is usually due to spinal lesions rather that renal ones * Urinary Incontinence * Usually E cuniculi * Can be induced by OVH, but corrected with diethystilbestrol * Psychogenic PU/PD reported in New Zealand whites * Scrotal/Inguinal Herniation of Urinary Bladder – diagnose with imaging, treat with surgery * Urinary Bladder Rupture – usually after trauma, surgery, flush abdomen, fix bladder * Urinary Bladder Eversion – can happen with parturition * Polypoid cystitis – may be induced by the sludgy urine * Tumors – low incidence, with nephroblastomas being the most frequent * Red Urine * Pigment v true hematuria * Pigmented urine lasts longer and stays colored after centrifugation and also fluoresces * Hematuria concentrates with centrifugation

Answer 42

**Dermatologic Diseases** -reviewed by ZCR Bacterial diseases * Subcutaneous abscesses * Common- skin wounds, dental disease, bacteremia * +/- adhered, nonpainful * **Lack myeloperoxidase** so pus is thick and caseous * Dx: aspirate using at least 22ga needle, scraping or section of capsule is most useful for bacteriologic analysis * **Tx: surgical excision is BEST** * If cannot remove all, marsupialize and manage as open wound * PMMA beads or calcium sulfate beads can be used * Cellulitis * Bacterial infection of the dermis and SQ fat, from tracking bacterial infections incl respiratory - Pasteurella, Bordetella, Staph aureus all common * Painful, erythematous, swollen area of skin * Cytology to guide abx * Parenteral abx with meloxicam * **MRSA** * **39% of clinically normal rabbits +ve in one study** * Cocci on cytology, resistant to abx- quinolones, penicillins, aminoglycosides, tetracyclnes and chloramphenical; sensitive to sulfas, doxy * **Moist dermatitis** * **Obesity, unspayed females with dewlap, urine scalding, dental dz** * ***Pseudomonas - blue green color* from pyocyanin pigment** * Tx - clip, clean skin with chlorhexidine, topicals (Domoboro’s sol’n, SSD cream) * Ulcerative pododermatitis * Avascular necrosis of the skin on the plantar and occ palmar feet * **Risk factors - rough flooring, inadequate bedding, obesity, poor mobility** * **Rex breed overrepresented** - lack guard hairs on feet * Difficulty lifting hock off the ground on hard floors, places pressure on superficial digital flexor tendon * Hair loss → erythema → infx of underlying bone. **Luxation of the SDF tendon can occur**, resulting in permanent disability. * Tx - mild cases - topicals, liquid bandages; advanced cases - wound care, sx debridement, bandaging. Analgesia if skin ulceration - meloxicam; opioids, tramadol, gaba if bone involvement. * **End stage is medial luxation of the SDF tendon - digits cannot be flexed when this happens, rabbit is forced into a plantigrade stance**. * Syphilis * **Spirochete Treponema paralysis cuniculi**. Mostly rabbit breeding colonies. NOT zoonotic. Transmitted sexually, direct contact of mother with young at birth. * swelling/redness of skin in anogenital region, also skin around eyes, nose, commisures of mouth - autoinfection. May be asymptomatic. * Dx - definitive - **ID organism in a lesion scraping by dark field microscopy** (lesions develop in 3-6 wks post infection). Serology is delayed and inaccurate. * **Pen G/procaine is the tx** * Necrobacillosis * Fusobacterium necrophorum - skin infection - swelling, abscesses, ulcers, necrosis * **Long, filamentous bacterial rods** on cytology; anaerobic culture of tissues confirms dx Fungal Diseases * Dermatophytosis * **Microsporum canis and gypsum in pet rabbits; Trichophyton in outdoor rabbits** * Asymptomatic carrier state, as high as 26% in wild rabbits * Predisposed due to fungistatic sebum * Early lesions - nasal planum, eyelids, pinnae, spreads to other areas by grooming * Dx - apple-green fluorescence under Wood’s lamp (M. canis only), DTM culture of fur, ELISA, bx * Self-limiting in healthy; tx with topical antifungals - clotrimazole, miconazole cream, 2% chlorhex BID, antifungal shampoo; if no response can rx a systemic antifungal i..e itraconazole, terbinafine, griseofulvin. Tx until 2 negative cultures, 7 days apart. Environmental decontamination with commercial disinfectants, 1:10 dilute bleach, or spray/foggers with enilconazole.

Answer 43

Parasitic Diseases * Ear Mites * *Psoroptes cuniculi*: * **A single, bell-shaped structure on end of the first two pairs of legs differentiates it from other psoroptiform mites** * Low grade subclinical infections, mild pruritus may be only sign * Early stages: dry grey-white to tan crusty exudate * **Exudate becomes darker, advances into ear canal and pinnae; can spread to head and neck, ears droop → excoriations, fur loss, secondary infections → vestibular signs** * Do not try to remove crusts without analgesics * Microscopic exam of crusts, ear wax * Tx - parasiticides - ivermectin, selamectin, moxidectin, moxidectin with imidcloprid, eprinomectin, fluralaner; decon envt with flea products * Fur Mites * *Cheyletiella parasitovorax*: * **Common nonburrowing mite of rabbits**, lives in superficial keratin of epidermis. More common in animals that cannot groom well, young, immune compromised * Mites MC in the dorsal neck, trunk * **White, flaky, dry dermatitis, pruritic, patchy alopecia. “Walking dandruff”** * Zoonotic! Causes a mild pruritic papular dermatitis. * Dx via microscopic exam of skin scrapings, acetate tape prep, flea comb * Saddle shaped with inward curving claws, hair-like setae at end of distal limbs * Tx with ivermectin or selamectin, lime sulfur drips or carbaryl flea powder * Other fur and skin mites * *Leporacarus (Listrophorus) gibbus*: nonburrowing, nonpathogenic fur mate of wild and domestic rabbits. Browse on surface keratin and sebaceous secretions. * **Nonpathogenic,** **can be spread to people**. * Brown, laterally compressed with short legs and single projections from the head * Same dx, tx as Cheyletiella * *Sarcoptes scabei var cuniculi* and *Notoedres cati* - both highly contagious, burrowing mites - lab, commercial rabbits MC * Highly pruritic, yellow, crusting dermatitis * ivermectin , other tx for Cheyletiella * *Demodex cuniculi* - thin elongated mite, obligate, host specific parasite of rabbits. * Alopecia, seborrhea, crusting dermatoisis of face, head an eck * Tx with ivermectin and amitraz * Fleas * **Ctenocephalides felis, C. canis, most common**; pregnant does, young animals MC affected * Dull coats, patchy alopecia, fleas transmit myxoma virus * Topical imidacloprid/permethrin, selemectin, oral lufenuron * Selamectin does not have prolonged residual activity in rabbits b/c of short half life compared with that in cats and dogs * Do NOT use fipronil * Lice * Rare in pet rabbits, usually poor husbandry related * Dx by finding lice and eggs * Ivermectin tx * Black Flies * spread myxoma virus, breed in water * Ticks * Rare in pet rabbits * Wild rabbits harbor both ixodid (hard) and argasid (soft-bodied) ticks, most common is continental rabbit tick *Haemophysalis leporispalustris* * Vectors of myxomatosis, Lyme disease, RMSF, Tularemia * Ivermectin single dose after manual removal to kill remaining * Myiasis * Caused by obligate host specific flies (i.e. Cuterebra) or facultative free living flies (Lucilia sp). * **Botflies (Cuterebra) - MC wild rabbits in late summer and fall; eggs laid near nests and larvae burrow into fur, enter body through nasal or oral; cysts form in ventral cervical region, axilla, rump, inguinal areas → as they mature a breathing hole/fistula forms** * Fly strike - predisposed by fecal/urine staining, obesity, inadequate grooming * Tx - remove larvae, extend breathing hole to remove the larvae whole. Wound care - clip, debride necrotic tissue, flush wound. Endoparasites of the Skin * Oxyuriasis * *Passalurus ambiguous* - rabbit pinworm, adults live in GI, eggs can cause perianal pruritus, nonpathogenic * ID eggs on tape strips from perianal skin or fecal samples * Tapeworms * IHs of many tapworms for which dogs and foxes are the DH * Eggs hatch in SI → larvae burrow in SC and IM tissues, cause cysts in different sites (retrobulbar space, cheek, axilla) * Surgical removal of the cyst is the treatment of choice

Answer 44

Viral Diseases * Myxomatosis * **Myxoma virus** - a **poxvirus** - found naturally in *Sylvilagus brasiliensis* (jungle rabbits) in Central and South America and brush rabbits in California * **Develop cutaneous fibromas, no systemic disease in these hosts, but pathogenic and fatal systemic disease in *Oryctolagus* rabbits** * **Inoculation via arthropod vectors → swelling of eyelids and ear margins → generalized facial swelling → genital swelling/ocular discharge, die from septicemia in severe cases** * Pyrexia, lethargy, systemic illness, skin nodules * Supportive care is the only tx * Recommended vaccination in UK, Europe * acute, peracute form caused by variant strain in southern CA., acute death * Shope Fibroma virus * **Tumorigenic poxvirus**, endemic in Sylvilagus spp. → biting mosquitoes spread to domestic rabbits → fibromatous skin lesions on feet/legs, occ face, back * Self limiting * Shope papilloma virus * Rare, likely inoculation from biting insects * **Keratinized papillomas around face and ears** * **Malignant transformation to SCC in Oryctolagus rabbits** * Oral papillomatosis * Wart-like lesions on oral mucosa * Direct contact, MC in young and immunocompromised * Rabbit pox * Eruptions over skin, mucous membranes, lethargy, pyrexia, lymphadenitis * Minimal risk in pet rabbits, mainly lab colonies Neoplasia * Primary skin neoplasms rare in rabbits, basal cell tumors most common Trauma * Barbering * Dominant animal overgrooms another * Self barbering in does in estrus * Maladaptive, low fiber diet * Medical tx usually not required * Self-mutilation * May be secondary to envtal stress * Genetic in lab rabbits * Provide supportive care, analgesia +/- abx if infected * Use only soft collars, most rabbits dont tolerate collars well Diseases of Unknown Origin * Sebaceous adenitis * **T-cell autoimmune rxn to sebaceous gland and hair follicle** * **Linked to thymoma, autoimmune hepatitis in rabbits** * **Nonpuritic, exfoliative dermatitis**, areas of alopecia, hair epilates easily with follicular casts (keratin debris on hair shafts) * Histo: orthokeratotic hyperkeratosis * **Tx with cyclosporine, miglyol successful** * Cutaneous Asthenia or Ehlers-Danlos-Like Syndrome * Skin fragility, hyperextensibility and joint laxity - easy skin tearing * Dermal fibrosis * Hormone-related**, fibrous dermal thickening of the dorsum - intact male rabbits** * Nonpruritic, no alopecia * Eosinophilic granuloma * Rare cutaneous rxn - red, ulcerated skin lesions assoc with ectoparasites, allergies * Dx via histopath * Allergic dermatitis/contact dermatitis * Direct contact with skin irritants * Remove the potential source, consider steroids * Intradermal skin testing not validated in rabbits

Answer 45

**NEUROLOGIC & MUSCULOSKELETAL DISEASES** - reviewed by ZCR Fungal Diseases * Encephalitozoonosis * *Encephalitozoon cuniculi* - **microsporidium, obligate intracellular pathogen** * Commonly chronic and subclinical infections * Median age 2.4 years * High prevalence in rabbit colonies * Transmission: 6 weeks from infected dam, spores ingested or inhaled; **oral ingestion from urine MC** * Spores have a polar filament that injects the sporoplasm into target cells - retciuloendothelial cells - initiating infection * Meronts differentiate via sporonts into infective spores (sporogony; acquire thick spore wall) → pseudocyst becomes overcrowded → cell rupture → systemic circulation of infective macrophages * **Most immunocompetent rabbits develop chronic, subclinical infections** * **Vestibular disease #1 neuro sign** * Head tilt, rolling * Central vestibular dz **can mimic peripheral** in these cases. **Central signs often lacking despite presence of central disease.** * **Otitis interna is #1 ddx and can be accompanied by facial hemiparesis or hemifacial dysfunction**, **not seen with E. cuniculi** * Cerebrum #1 location affected in brain, followed by leptomeninges * **Histo lesions not always indicative of overt encephalitozoonosis as the cause for neuro signs** * Most rabbits in one study showed perivascular inflammatory infiltrates * Antibodies develop 3-4 wks post infection, highest at 6-9 wks * Dx: * **PE, serology, r/o other ddx** (otitis interna, suppurative meningoencephalitis, trauma, brain tumor) * **Serology indicates exposure, doesn’t diff b/w active and latent infx**. **A negative titer generally rules out *E. cuniculi* as cause for neuro signs** since seroconversion occurs several weeks before organism reaches CNS. * IgM rises in acute stages - minor importance for detection in this disease * Other methods: urine Ab levels, plasma or serum protein electrophoresis, C-reactive protein, CSF analysis * Increased Ab in asymptomatic rabbits * Abnormalities in protein electrophoresis seen, but not specific * C-reactive protein can have a high specificity and positive predictive value * CSF shows lymphomonocytic pleocytosis and increased protein concentrations -nonspecific * PCR remains unreliable * E cuniculi is an opportunistic pathogen in immunocompromised humans * Treatment/control * Challenging to report tx success - latent infections, some resolve spontaneously * **Benzimidazoles drug of choice, adverse effects include BM suppression and intestinal tract crypt necrosis** * Systemic steroids - has shown benefit if fenbendazole started 7 days prior contentious * Antiemetics not indicated, nausea not assoc with torticollis

Answer 46

Parasitic Diseases * Neural Larva Migrans * Baylisascaris sp reported NLM in rabbits * Reported where raccoons live, important cause of NLM and ocular LM in humans * Rabbits are **paratenic hosts**, become infected when they **ingest vegetation, hay or bedding contaminated with raccoon feces** **carrying Baylis eggs** → larvae migrate to other tissues, predilection for CNS (track like lesions in CNS tissues) * Neuro signs- swaying and falling are pronounced. May show improvement, or be rapidly progressive. * Dx - based on poss exposure and c/s, antemortem challenging * Albendazole and steroids in people, oxibendazole has had success in rabbits * Cuterebra * Pupate in subcitis, also migrate to ear canals, CNS causing neuro signs * Toxoplasmosis * Rare in rabbits * Nonspecific neuro signs - tremors, ataxia, posterior paresis, paralysis, tetraplegia * Serologic testing - exposure only * **Tx: TMS and pyrimethamine or doxy**, NOT clindamycin (GI dysbiosis and death) Bacterial Diseases * Otitis Media-Interna * Vestibular signs, head tilt, rolling * **Lops are predisposed** because the ear canal is folded and stenotic * Bacterial otitis interna historically assoc w/ Pasteurella * **Primary OM can be assoc with URI** migrating to middle ear via Eustachian tube * Can also spread to inner ear or external ear canal * **Facial nerve deficits\*\*\*** * Dx - c/s, skull rads, CT, endoscopy * Tx - sx in advanced cases, abx long term (4-8 wks) * Bacterial Infections of the CNS * Primary suppurative encephalomyelitis * Staph species, Pasteurella * **Otogenic intracranial infection as an extension of otitis media common,** peripheral → central vestibular signs Viral Disease * Rabies * Rarely reported in rabbits - 30 cases between 1971-1997 - most were in cases where racoon variant was enzootic * Paralysis or paresis of one or more limbs, head tremors * No rabies vaccine approved, protect outdoor rabbits from contact with wildlife * Herpes simplex virus (HSV) * Rare but HSV encephalitis reported. Transmission from people to rabbits is likely, as most cases occurred in assoc with humans with herpes labialis * Nonsuppurative meningoencephalitis of the grey matter o the cerebral hemispheres. * Circling, spinning, hypersalivation, seizures * This virus is consistent with HSV (herpes simplex virus) in humans Trauma * Vertebral fracture or luxation * Most common cause of acute posterior paralysis; fractures \>\> dislocations, **Lumbosacral (L6-L7) is the MC site for fracture** * Heavily muscled hindquarters twist about the LS junction, often frightened, improper handling * Paraplegia, loss of deep pain, skin sensation, motor control of urinary bladder and anal sphincter depending on compromise to spinal cord * Radiographs to confirm * Tx * Moderately affected rabbits can respond to conservative management - weeks to months of strict cage rest. Analgesics, anti-inflammatories. * Bladder expression if indicated * Decubitus ulcers often develop * Can be fitted with a cart to permit movement Degenerative Disorders * Osteoarthritis, Spondylosis, IVDD * Age-related OA * **MC sites: elbows and stifles** * Sponylosis deformans: degenerative spinal disease resulting in ankylosis of the vertebral joints * **MC in cervical vertebrae** * Risk factors: trauma, genetic predispositions, obesity, old age * Kyphosis, lordosis, scoliosis, hemivertebrae are common in pet rabbits * Spontaneous degenerative changes seen in lab rabbits * Chondroid metaplasia of nucleus pulposus throughout vertebral column by 2 years * Calcification of the NP in the caudal thoracic spine * Spondylosis in cervicothroacic spine * Disc protrusion can mimic signs of spinal fracture/luxation * c/s of MS pain- decreased grooming, abnormal gait/mobility, perineal soiling, unkempt coat, uneaten cecotrophs * Spinal pain assoc with aggression, reduced GI motility * Dx * Radiographs: * OA - capsular swelling, osteophytosis, thickening of surrounding soft tissues, narrowed joint spaces * Spondylosis deformans: spinal exostoses, narrowed disc spaces, calcification of nucleus pulposus * MRI necessary to confirm spinal cord compression * Therapy * Excellent response to meloxicam and tramadol * Gabapentin suggested * Adequan, glucosamine and sodium chondroitin sulfate - nutraceuticals * PT * Environmental modification - reducing need to climb stairs, climb furniture, providing ramps, nonslip surfaces * 51 acupoints described in the rabbit, a Yin species (parasympathetic dominates) - acupoints around neck, shoulders and back are good place to start, avoid paws * The following acupoints have also been described in the * Rabbit76: * Seizure: Da-feng-men, Nao-shu, LIV-3 * Coma: GV-26, PC-6/TH-5, KID-1, PC-8, HT-9 * General weakness: LI-10, ST-36 * Splay Leg * Developmental musculoskeletal condition of young rabbits or older, sedentary rabbit * **Housing on slippery floors and inability to adduct one or more limbs** * Hind limbs in younger rabbits more affected - **flattening/reduction of femoral head, subluxation of the hip, valgus deformity, patellar luxation** * Can treat early cases via splinting and changing flooring * **Abduction of forelimbs in older rabbits - long term inactivity and associated muscle wasting can lead to this. Obesity and OA may contribute.** * Hereditary Cerebellar Degenerative Disease * Cerebellar cortical abiotrophy, degenerative disease of the cerebellium, reported in a litter shortly after birth from a single pair of breeding rabbits * Radial Hemimelia * Reported in a 1.5 mo old rabbit presented with acute lameness after a fall * Hemimelia: complete or partial absence of one or more bones of the limbs

Answer 47

Toxicities * Lead toxicosis * Neurologic signs in rabbits can occur, but anemia, anorexia, depression, loss of body condition and GI stasis are more common * Signs result from CNS edema and hypoxia * Sources-household paint (before 1978), old glazed ceramic dishes, old linoleum, stained glass solder, lead weights in curtain hems * **Anemia, nucleated RBCs, retics, basophilic stippling, hypochromasia** * Dx - rads to r/o metal FB, measure blood lead conc. \>10ug/dL indicates tx * Chelation with Ca EDTA, repeat blood lead levels, 2 courses of tx (5-7d each) may be required * Fipronil Toxicosis * Anorexia, lethargy, fatal seizures * Guarded prognosis for recovery if already showing c/s * If acute, bathe to remove fipronil * Midazolam for seizures, supportive care PRN (IVF, feedings) * Pyrethrin/permethrin * Some ectoparasiticides may cause anorexia, lethargy, muscle twitching and seizures when applied to rabbits * Similar tx to fipronil Metabolic Disorders * Pregnancy Toxemia * Rare, usually late gestation in obese, multiparous does * Neuro signs in severe cases (depression, incoordination, convulsions, coma), can also be asymptomatic * **Risk factors: obesity, decreased dietary intake** * **Pathology: hepatic lipidoses and necrosis (severe), fatty changes in kidneys, heart, adrenal glands, liver** * Tx: treat electrolyte disturbances, IVF w/ glucose * **Provide a high energy palatable diet during gestation** * Heat stroke/stress * Rabbits prefer \<80F and are very susceptible to heat stroke/stress * Emit body heat through pinnae and feet, incr temps → SNS-mediated vasodilation and incr blood flow to pinna, skin → stress or prolonged chronic high temps/humidity → vasoconstriction and inhibition of physiologic cooling → pathologic hyperthermia * c/s: weakness, depression, incoordination, seizures, coma with temps \>105F * Tx: cool with fans, spray with water, wrap in wet towels; STOP cooling at 102F * Midazolam, hypertonic saline for cerebral edema (crystalloids + colloids) Nutritional Disorders * Vitamin E- * Deficiency: **nutritional muscular dystrophy** - clinical paresis from degeneration of skeletal muscle fibers. Can occur with prolonged storage of feeds. Recommend fresh pellets. * Vitamin A * **Hypovitaminosis A - hydrocephalus** from defective bone through, stenosis of cerebral aqueduct * Vitamin D * Excess - resorption of bones, calcification of soft tissues (arteries, liver, kidneys) * Calcium * Deficiency - nutritional hyperparathyroidism - enlarged joints, crooked backs, arched backs and enlarged rib costochondral jxns in young rabbits; demineralization of bones and pathologic fx in adults. * hypoCa in does - weakness, paresis, recumbency * Manganese * Brittle bones and limb problems, has a coenzyme for cartilage formation * Magnesium * Deficiency - seizures * Potassium * Deficiency - muscle weakness and paralysis Other Misc Diseases * Neoplasia * **MC cause of CNS neoplasia = Lymphoma** * Others: teratomas, ependymoma, plasma cell myeloma, neuroblastoma * Osteosarcomas reported - usually assoc with facial bones, mets in lungs, heart, liver, kidneys, pericardium * Vascular * Cerebrovascular accidents suspected in sudden loss of motor fxn * Supportive care can recover fxn * Idiopathic * 16/118 rabbits in one study for neuro signs could not have a cause identified * “Floppy rabbit syndrome” - acute tetraplegia with generalized lower motor neuron signs; clinically normal other than paralysis, will eart and drink on their own, can urinate/defecate * No evidence of Toxo or E cuniculi, CK elevated on biochem * Miscellaneous * Neuro signs assoc w/ listeriosis * Seizures - hypoxia secondary to empyema, pneumonia, metastatic tumors, azotemia

Answer 48

Ferrets, Rabbits, and Rodents **Chapter 20 - Lymphoreticular Disorders, Thymoma, & Other Neoplastic Diseases** * Histopathologic diagnosis from tissue biopsy needed to make diagnostic and therapeutic decisions but cytologic results of FNA may be sufficient when accurate diagnosis is possible * For locally aggressive tumors, surgical resection and/or radiation therapy indicated depending on tumor type, location and ability to obtain clean margins. * Chemotherapy indicated for systemic neoplasia _Lymphoreticular Neoplasia_ * **Most cases diagnosed as generalized or multicentric lymphoma, but cutaneous lymphoma, lymphoid leukemia, thymic lymphoma and thymomas are described with varying incidence** * Cause of lymphoreticular neoplasia unknown and likely multifactorial * Strain susceptibility assoc with autosomal recessive genes Is in wirehair rabbits with generalized lymphoma seen at 5-13 months old * Have not confirmed role of an oncogenic retrovirus _Multicentric lymphoma_ * **Most common type of lymphoproliferative disease in rabbits, seen in several breeds (NZ white, Japanese white, Dutch and Netherland Dwarf) and can occur in all ages (\<1 yr to geriatric)** * Can be T or B cell, **but B cell more common** * **Cx: anorexia, lethargy, emaciation, pallor, diarrhea, exophthalmos, upper respiratory stridor, rhinitis depending on organ involvement/location** * Biochem – may be unremarkable or see increases in AST, CK, BUN, Crea. * **CBC – moderate to severe anemia - in young rabbits fluctuating and depressed Hct may be an early indication of lymphoma**. * Typically normal twbc but see relative predominance of lymphoid cells, including immature and atypical cells * Common sites affect on necropsy: LN, GI, kidneys, liver, spleen, adrenal glands, gonads, bone marrow _Cutaneous Lymphoma_ * **Usually primary but can be secondary to multicentric involvement** * Two types differentiated histologically and immunohistochemically * Epitheliotrophic – T cells infiltrate epidermis and adnexal structures * Nonepitheliotropic – B cell infiltrate middle and deep dermis * Have the potential to metastasize to internal organs * More commonly reported in Europe than US; genetic/extrinsic factors may play a role * **Affects all ages (7 mo to 9yr)** * **Cx: solitary or multiple subcutaneous nodules in multiple locations, erythematous alopecia, and hemorrhagic crusts on chin/neck, blepharitis or nonpruritic alopecia** _Leukemia_ * Lymphoid leukemia – proliferation of neoplastic lymphocytes that typically originate in the bone marrow and occasionally the spleen. * **Neoplastic cells may or may not be in circulating blood** * **Twbc counts ranged 30k-100k and in all reports, neoplastic cells seen in BM and LNs** _Thymic lymphoma_ * Neoplasm of T lymphocyte origin, possibly with other organ or systemic involvement * Present similar to thymoma, paraneoplastic syndromes (chylothorax and exfoliative dermatitis) have been reported _Thymoma/Thymic Carcinoma_ * Rabbits have persistent large thymus cranioventral to hear and extending into thoracic inlet * **Adults can have hyperplastic thymus (enlarge 3-4x normal), grossly resembling tumor but with no neoplastic criteria on histologic exam** * **Thymoma – slow growing and benign, mix of lymphoid and epithelial cells** * **More common and higher incidence in older rabbits (no breed/sex bias)** * **Thymic carcinoma – malignant cytologic features, more likely to metastasize** * Differentiation is based on morphologic and histologic features * **Cx: Presence of mediastinal mass usually causes difficultly breathing (hyperpnea, open mouth breathing). Often seen nasal flaring, increased respiratory rate and effort on PE. Uniquely, may have exophthalmos (that can be retropulsed) or prolapse of third eyelids** * May hear muffled lung sounds over anterior mediastinum and decreased compressibility of thoracic cavity in smaller breeds * **Cranial vena caval syndrome – space occupying mass compressing vessels of anterior thorax causing changes in blood pressure and impeding vascular return to the heart** * Paraneoplastic syndrome – thymoma rabbits may have scaling, dermatitis, or sebaceous adenitis. Thymoma associated exfoliative dermatitis * Can have normal CBC, leukocytosis (lymphocytosis \>70% small lymphs), or anemia. _Diagnosis of Lymphoproliferative Disorders and Thymic Masses_ * Basic – CBC, Chem, thoracic and abdominal rads * Leukocytosis w/ mature lymphocytosis, inverse H/L ratio, or anemia * Abdominal ultrasound with FNA of mass/enlarged LNs * **CT with contrast recommended for thoracic mass or if unavailable, thoracic u/s** * **Epithelial cells usually poor exfoliation and cystic fluid may be nondiagnostic** * **Thymoma – mixed population small to intermediate mature lymphocytes and epithelial cells** * **Lymphoma – intermediate to large lymphoblasts** * Biopsy often needed for definitive diagnosis _Treatment of Lymphoproliferative Disorders_ * Long term prognosis of lymphoma and other lymphoid disorders with treatment guarded to poor * Chemotherapy: * Cyclophosphamide, Vincristine, Prednisolone with or without doxorubicin and L asparaginase have been used with limited success. * **Must weigh potential risks of treatment with lack of data on efficacy of chemo** * Case report of mediastinal lymphoma responding to lomustine but died or renal failure * **Immunosuppression by chemo or steroids can give rise to lethal encephalitozoonosis in subclinical rabbits** – consider testing serology * Adverse effects: anemia, enteritis, typhlitis, and nephrotoxicity * In rabbits, Vincristine – neurotoxic, doxorubicin – aplastic anemia, L-asparaginase IV – diabetic syndrome, repeated cyclophosphamide – renal failure _Treatment Options for Thymomas_ * Radiation * Similar action of radiation therapy across species * CT w/ or w/o MRI vital for planning radiation, surgery, or both * **Radiation of lymphocytes results in fast depletion via apoptosis – tumors with high lymphocyte population shrink down more quickly and dramatically** * Epithelial cell population shrink more slowly or not at all * **Surgery is questionable in rabbits due to high perioperative risk of thoracotomy. Mutidose radiation therapy favored over surgery, and is considered first treatment of choice in rabbits** * Intensity modulated radiation therapy – method of choice because it delivers better dose to tumor and significantly reduces exposure to adjacent organs * **MST with radiation reported ~1yr, with response times of 4d to 40 days with tumor volume shrinking \> 30%** * **Adverse effects – alopecia, radiation induce pneumonitis and myocardial failure** * Due to fast tumor shrinkage, must re-image to adjust radiation planning, especially if highly lymphocytic cell population * Volumetric arc technology (VMAT) had MST of ~2 yr, no side effects, and 100% complete response within 6 months. More expensive technology. Radiation plan adjustments made in all cases. * Surgery * High risk of surgical or anesthetic death * **Acute perioperative death is the most common risk associated with surgical excision – mass often impinged on lung when placed in dorsal recumbency thus intubation and short anesthesia necessary** * Aspiration * **Thymomas can be primarily cystic or solid. Removal of fluid in cystic thymomas may alleviate dyspnea and improve quality of life for palliative treatment**. Can be repeated every 3-6 months for symptomatic relief for 8-12 months on avg. _Other Neoplastic Diseases_ * The most common organs systems of primary tumors in rabbits are reproductive, skin and subcutaneous tissues. * Reproductive * Uterine adenocarcinoma is most common neoplasm in doe (other uterine neoplasms – leiomyosarcoma, leiomyoma, choriocarcinoma, hemangiosarcoma, deciduosarcoma, mixed Mullerian tumors * Mammary gland adenocarcinoma in does often associated with uterine disease * Cystic mammary dysplasia and adenocarcinoma associated with high serum prolactin levels from prolactin secreting pituitary adenomas * Interstitial cell tumor most frequent testicular neoplasia (other – seminoma, serotli cell, granular cell and teratoma * Skin and Subcutis * Trichoblastoma (prev basal cell tumor) – most common cutaneous neoplasm in rabbit * Melanoma uncommon but can involve ear pinnae, eyelid, head, peri-vulvar, thigh, stifle, scrotum * Other primary tumors * Osteosarcoma most common bone tumor in rabbits * Nephroblastoma or embryonal nephroma is benign tumor associated with polycythemia **_Diagnostics_** * Venipuncture and injection sites (F8): * Marginal auricular veins and central auricular arters (**fluids only**) * Jugular and cephalic (**catheters**), saphenous (**venipuncture**)

Answer 49

**Bilateral pararhinotomy with middle meatal antrostomy of the maxillary sinus in a rabbit with chronic rhinitis** JAVMA 2019 Relevant anatomy – Paranasal cavities are paired comprise a dorsal conchal sinus, large maxillary sinus with a dorsal and ventral recess, and a sphenoidal sinus. - Maxillary sinuses largest, extend from facies cribrosa to rostral orbital edge. - Dorsal recess of each maxillary sinus ovoid shape, located lateral to middle nasal meatus and ventral to dorsal conchal sinus. - Ventral recess of maxillary sinus localted ventral and medial to dorsal recess, with ventral edge against the alveolar bulla of maxillary premolar teeth. - Dorsal and ventral recesses connect through an opening in the rostral half of the dorsal recess of the conchomaxillary cavity. - Conchomaxillary cavity opens into middle nasal meatus through area of dorsal recess of the maxillary sinus. - Ostium maintains pressures between nasal cavities, allows ventilation of conchomaxillary cavity and clearance through mucociliary transport. With maxillary sinusitis, maxillary sinus ostium may become occluded. - Develops positive pressure followed by negative pressure, reduces mucociliary function and facilitates bacterial adherence and development of secretions. - Inadequate ventilation contributes to development and reduced oxygen tension following obstruction of maxillary sinus ostium facilitates growth of facultative anaerobes. - Reduced mucociliary transport in the sinuses decreases clearance of pathogens. - Chronic sinusitis may be assoc with dental disease, trauma, neoplasia, FB. - May develop secondary otitis media due to connection to nasal cavity through nasopharyngeal meatus and Eustachian tubes. CT > MRI for chronic disease, may not reflect acute changes in mucosa during early disease. Deep nasal swab culture recommended in management of chronic sinusitis/rhinitis in rabbits. - Most common organisms include Pasteurella multocida, B. bronchiseptica, Pseudomonas, Staphylococcus. - Most common mix is P multocida and B bronchiseptica. - B Bronchiseptica is common in rabbit resp tract, may not induce disease. Lateral approach for pararhinotomy chosen over dorsal approach because it was considered less invasive and faster.

Answer 50

Homer, L. M., & Bacon, N. J. (2021). **Hemipelvectomy to treat sarcoma of the proximal portion of the femur in a rabbit**. Journal of the American Veterinary Medical Association, 258(2), 192-196. Case Description: A 7-year-old sexually intact female rabbit was admitted to the hospital because of a 6-month history of chronic right pelvic limb lameness. Clinical Findings: Clinical examination revealed a prominent right pelvic limb lameness and signs of pain on manipulation of the right hip joint, with a focal, well-defined soft tissue mass palpable in the right pelvic area. Pelvic radiography revealed a lytic hip joint lesion and CT detailed an expansile lesion within the proximal portion of the femur with an appearance consistent with a soft tissue mass. Histologic evaluation of incisional biopsy samples of the soft tissue mass revealed a poorly differentiated sarcoma. Treatment and Outcome: A hemipelvectomy was performed, and histologic evaluation of the soft tissue mass confirmed the diagnosis, with tumor-free margins achieved. The patient recovered well from surgery and had good mobility. The patient survived 21 months after surgery and died of a non–cancer-related disease. Anatomic dissection was described in a cadaver rabbit to aid future surgeries. Clinical Relevance: To the authors' knowledge, this was the first report of a hemipelvectomy performed in a rabbit. Hemipelvectomy is more routinely performed in canine and feline patients, but with the right candidate and owner commitment to aftercare, it may be safely and successfully performed in rabbits. Key Points: ● Right-sided hemipelvectomy performed to remove a sarcoma of the proximal femur/hip with margins. ● Ventral paramedian approach with a curvilinear incision from the inguinal fold to the ischium. ● Sartorius, adductor, gracilis, pectineus, medial aspect of the tensor fascia latae transected proximally to expose the pubic symphysis. ● Femoral artery and vein individually double ligated proximal to the femoral triangle. ● Rectus abdominus and linea alba transected at insertions on cranial pubic symphysis. ● Iliopsoas muscle transected close to insertion on the lesser trochanter of the femur, several cm from the tumor. ● Lateral skin incision made joining ends of the previous medial incition. Superficial gluteal, biceps femoris, lateral aspect of the tensor fascia latae, and coccygeofemoral muscles transected. ● Pubis cut paramedian at the cranial and caudal edges of the right obturator foramen, disarticulated the sacroiliac joint. ● Transected branches of the lumbosacral plexus close to the pelvic limb and removed en bloc. ● Opposed thoracocolumbar fascia with the external abdominal oblique and rectus abdominus muscles to close, followed by SQ tissue and skin. ● Only intraoperative complication was mild hemorrhage, controlled with pressure and cautery. ● Follow-up: Did well, occasionally would fall to the right side although mobility remained good. Some issues with flexibility/ability to groom and perform coprophagia. ● Limb amputation in rabbits described with those of appropriate body weight, younger, and without pododermatitis before surgery having a better outcome. Most common complications are difficulty ambulating, issues with hygiene/grooming, and pododermatitis. ● Muscle mass around the hind limb is proportionally larger in rabbits vs dogs and cats. Sartorius has a much smaller diameter and 1 segment instead of 2. Lateral musculature i.e. coccygeofemoral muscle originates from the craniolateral sacrum and inserts on the lateral condyle of the tibia. Skin is much thinner. Takeaways: Hemipelvectomy may be a safe and viable option for rabbits. Complications include difficulty ambulating, issues with grooming, and pododermatitis.

Answer 51

Kabakchiev, C. M., Zur Linden, A. R., Singh, A., & Beaufrère, H. H. (2020). **Effects of intra-abdominal pressure on laparoscopic working space in domestic rabbits (Oryctolagus cuniculus)**. American Journal of Veterinary Research, 81(1), 77-83. OBJECTIVE To assess the effects of 3 intra-abdominal pressures (IAPs) on pneumoperitoneal (laparoscopic working space) volume in domestic rabbits (Oryctolagus cuniculus). ANIMALS 6 female New Zealand White rabbits. PROCEDURES A Latin-square design was used to randomly allocate sequences of 3 IAPs (4, 8, and 12 mm Hg) to each rabbit in a crossover study. Rabbits were anesthetized, subumbilical cannulae were placed, and CT scans were performed to obtain baseline measurements. Each IAP was achieved with CO2 insufflation and maintained for ≥ 15 minutes; CT scans were performed with rabbits in dorsal, left lateral oblique, and right lateral oblique recumbency. The abdomen was desufflated for 5 minutes between treatments (the 3 IAPs). Pneumoperitoneal volumes were calculated from CT measurements with 3-D medical imaging software. Mixed linear regression models evaluated effects of IAP, rabbit position, and treatment order on working space volume. RESULTS Mean working space volume at an IAP of 8 mm Hg was significantly greater (a 19% increase) than that at 4 mm Hg, and was significantly greater (a 6.9% increase) at 12 mm Hg than that at 8 mm Hg. Treatment order, but not rabbit position, also had a significant effect on working space. Minor adverse effects reported in other species were observed in some rabbits. CONCLUSIONS AND CLINICAL RELEVANCE A nonlinear increase in abdominal working space was observed with increasing IAP. Depending on the type of procedure and visual access requirements, IAPs > 8 mm Hg may not provide a clinically important benefit for laparoscopy in rabbits. ● Which IAP provides greatest increase in working space with minimizing adverse effects on cardiorespiratory function and local tissue perfusion ● Working space – volume of abdominal space created by insufflation to allow visual access ● Depends on patient size, GI contents, organomegaly, IAP, patient ventilation, and muscle tone effects of anesthetic protocol ● CT scans prior to cannula placement and then scans in each position at each IAP ● Imaging software to convert images to 3D models ● Positioning (dorsal, left lateral, or right lateral) did not affect laparoscopic working space ● Significant effect of IAP on working space volume – 4mmHg << 8mmHg << 12mmHg ● Order of treatment had an effect of working space volume ● IAP of 4mmHg, working space was lower when applied first than applied second or third ● IAP of 8mmHg, difference in working space when applied second than applied first or third ● May be due to prestretch phenomenon ● After insufflation to 8 or 12mmHg all rabbits were apneic and had increased ETCO2 (50-60 mmHg) ● Adverse effects: mild GI signs, SQ emphysema due to inappropriate cannula placement Take home: May not be advantageous to use IAP >8 mmHg

Answer 52

**ASPIRATION BRONCHOPNEUMONIA BY ACINETOBACTER BAUMANNII IN A WILDLIFE EUROPEAN HARE (LEPUS EUROPAEUS) IN BRAZIL** David G. Pereira, Elizabeth Batista, DVM, MSc, Thierry G. de Cristo, DVM, MSc, Fa ́bio Santiani, DVM, Ricardo A. P. Sfaciotte, DVM, MSc, PhD, Sandra M. Ferraz, DVM, MSc, PhD, Aury N. de Moraes, DVM, MSc, PhD, and Renata A. Casagrande, DVM, MSc, PhD Abstract: **Acinetobacter baumannii is a major cause of illness in hospitalized patients and the most important and common pathogen in nosocomial outbreaks worldwide**. In animals, A. baumannii has been associated with respiratory infections in a group of minks, leading to pneumonia and acute mortality. **This report documents a case of aspiration bronchopneumonia in a wild European hare caused by A. baumannii.** A free-ranging, adult male European hare was submitted to necropsy after acute trauma due to being hit by a car. Its lungs showed consolidation with abscess in the middle and cranial lobes. Histopathologic evaluation revealed liquefactive necrosis associated with neutrophilic infiltration, cellular debris, plant material, and bacterial myriads surrounded by moderate neutrophils, macrophages, multinucleated giant cells, lymphocytes, and plasma cell inflammation. Acinetobacter baumannii was isolated from lung tissue. Journal of Zoo and Wildlife Medicine 51(1): 253–256, 2020 Brief communication: - Acinetobacter baumannii = cause of nosocomial infections in hospitalized people -- Multi-resistant strains important 🡪 pneumonia in ICU -- Rare reports in animals with pneumonia but has also been isolated from fecal samples of wild birds -- Opportunistic, aerobic, pleomorphic, nonmotile, gram-negative bacillus -- Found in soil + water, isolated from nonhuman sources such as animals, lice, vegetables, aquaculture - European hare (adult male) hit by car and sent to pathology lab for necropsy (Brazil) -- Good BCS, multiple fractures + luxations -- Middle lobe of the lung had an abscess, cranial lobes had consolidation -- Adhesion of the pericardial sac and the parietal pleura - Histopath lesions -- Liquefactive necrosis in the middle + cranial lung lobes - Culture of the lung = A. baumannii and E.coli - Likely died from hypovolemic + neurogenic shock secondary to trauma; aspiration bronchopnuemonia presumed to be incidental, or could have been a predisposing factor to the trauma - Unknown if the European hare is the natural reservoir for the bacteria, or if infection occurs from exposure to hospital contamination - Hare may have contact with native and domestic animals, humans - A. baumannii reported in European minks with hemorrhagic pneumonia

Answer 53

Cutler, D. C., Koenig, A., Di Girolamo, N., & Mayer, J. (2020). **Investigation for correction formulas on the basis of packed cell volume for blood glucose concentration measurements obtained with portable glucometers when used in rabbits**. American Journal of Veterinary Research, 81(8), 642-650. Objective: To determine effects of PCV on blood glucose (BG) concentration measurements obtained with a human portable blood glucometer (HPBG) and a veterinary portable blood glucometer (VPBG) on canine (cVPBG) and feline (fVPBG) settings (test methods) when used in rabbits and to develop correction formulas to mitigate effects of PCV on such measurements. Sample: 48 resuspended blood samples with known PVCs (range, 0% [plasma] to 92% [plasma and packed RBCs]) from 6 healthy research rabbits (experimental sample set) and 252 historic measurements of BG concentration and PCV in 84 client-owned rabbits evaluated at a veterinary hospital (validation data set). Procedures: Duplicate measurements of BG concentration with each test method and of PCV were obtained for each sample in the experimental sample set, and the mean results for each variable for each test method and sample were compared with results from a clinical laboratory analyzer (reference method) used to determine the true BG concentration for each sample. Mean ± SD differences in measurements between the reference and test methods were calculated. Linear regression and modified Clarke error grid analysis were used to develop correction formulas for the test methods given known PCVs, and these formulas were evaluated on the validation data set with linear regression and a modified Clarke error grid. Reslts: Blood glucose concentrations were falsely low for cVPBG and fVPBG used on samples with PCV < 31% and were falsely high for all test methods used on samples with PCV > 43%. Compared with original measurements, formula-corrected measurements overall had better agreement with reference method measurements for the experimental sample set; however, only the formula-corrected HPBG measurements had improved agreement for the validation data set. Conclusions and Clinical Relevance: Findings indicated that, in rabbits, HPBG measurements had improved accuracy with the use of the correction formula HPBG measurement of BG concentration + ([0.75 × PCV] − 15); however, the correction formulas did not improve the accuracy of VPBG measurements, and we believe that neither the cVPBG nor fVPBG should be used in rabbits. Key Points: - BG measurements with portable glucometers typically falsely lower for hemoconcentrated samples and falsely higher for hemodilute samples. Also reported in rabbits. - Measured BG in duplicate and PCV in triplicate for whole blood samples: -- BG measured with HPBG and VPBG on canine and feline settings. - Validation data set was an external data set of historic BG concentration measurements from a previous study of healthy and diseased rabbits at a vet hospital. - Correction form was developed. - HPBG yielded results more consistent with the LABgluc results vs VPBG, consistent with previous studies in rabbits. - A study showed that BG is assoc with prognosis and tx in clinically ill rabbits and rabbits with BG > 360 mg/dL had worse prognoses. Mean BG was 445 mg/dL with GI obstruction vs 153 mg/dL with stasis. - Another study showed hyponatremia < 129 mEq/L had 2.3 x increased risk of death within 7 days after clinical presentation.

Answer 54

Oura, T. J., Graham, J. E., Knafo, S. E., Aarsvold, S., Gladden, J. N., & Barton, B. A. (2019). **Evaluation of gastrointestinal activity in healthy rabbits by means of duplex Doppler ultrasonography**. American journal of veterinary research, 80(7), 657-662. OBJECTIVE To use duplex Doppler ultrasonography to compare gastrointestinal activity in healthy sedated versus nonsedated rabbits and to evaluate agreement between B-mode and pulsed-wave Doppler (PWD) ultrasonographic measurements. ANIMALS 10 healthy client-owned rabbits brought for routine physical examination and 11 brought for routine ovariohysterectomy or castration. PROCEDURES Duplex Doppler ultrasonography of the gastrointestinal tract was performed once for the 10 rabbits that underwent physical examination and twice (before and after presurgical sedation) for the 11 rabbits that underwent routine ovariohysterectomy or castration. Mean number of peristaltic contractions during a 30-second period was determined for the stomach, duodenum, jejunum, cecum, and colon from B-mode and PWD ultrasonographic images that had been video recorded. Findings for the duodenum and jejunum were compared between B-mode and PWD ultrasonography and between sedated and nonsedated rabbits. RESULTS Duodenal and jejunal segments had measurable peristaltic waves; however, the stomach, cecum, and colon had no consistent measurable activity. B-mode and PWD ultrasonographic measurements for the duodenum and jejunum had high agreement. No significant difference was identified between nonsedated and sedated rabbits in mean number of peristaltic contractions of the duodenum or jejunum. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that both B-mode and PWD ultrasonography of the duodenum and jejunum may be suitable for noninvasive evaluation of small intestinal motility in rabbits and that the sedation protocol used in this study had no impact on measured peristaltic values. Key Points - US assessment of GIT difficult because of GI gas accumulation - Traditional B-mode US - generates grayscale image based on amplitude and depth of returning echoes - Doppler US - identifies shift in sound frequency of moving target within an imaged area; quantitative, providing velocity of returning echoes - Pulsed-wave Doppler US - allows identification of Doppler shift from specific depth or location, with Doppler shift displayed as graph mapping velocity over time - Duplex Doppler US - consists of simultaneous display of real-time B-mode and PWD images, used to provide subjective (B-mode) and more quantitative (PWD) analysis of GI peristalsis -- Helps differentiate b/w mechanical and paralytic ileus - Objective: assess utility of duplex Doppler US for evaluation of GI activity in healthy non-sedated and sedated rabbits and evaluate agreement between B-mode and PWD US measurements - Methods – 10 non-sedated and 11 sedated (torb/midaz/ketamine) rabbits underwent duplex doppler US of GIT - Mean # of peristaltic contractions during 30-sec determined for stomach, duodenum, jejunum, cecum, and colon from B-mode and video recorded PWD US images - Only duodenum and jejunum had evidence of reliable propulsive contractions - No significant difference observed in # of peristaltic contractions in duodenum and jejunum as identified via B-mode versus PWD US or in sedated vs nonsedated rabbits -- sedation had no obvious adverse impact on US identification of peristalsis -- lack of reliably identified motility in stomach, cecum, and colon -- some rabbits in study had no duodenal or jejunal peristaltic contractions 🡪 more research needed to make clinical decisions

Answer 55

Bateman, F. L., Kirejczyk, S. G., Stewart, G. V., Cutler, D. C., Quilling, L. L., Howerth, E. W., & Mayer, J. (2019). **Effects of an enrofloxacin–silver sulfadiazine emulsion in the ears of rabbits with perforated tympanic membranes**. American journal of veterinary research, 80(4), 325-334. OBJECTIVE To determine whether an enrofloxacin–silver sulfadiazine emulsion (ESS) labeled for treatment of otitis externa in dogs has ototoxic effects in rabbits following myringotomy. ANIMALS 6 healthy adult New Zealand White rabbits. PROCEDURES Rabbits were anesthetized for brainstem auditory-evoked response (BAER) tests on day 0. Myringotomy was performed, and BAER testing was repeated. Saline (0.9% NaCl) solution and ESS were then instilled in the left and right middle ears, respectively, and BAER testing was repeated prior to recovery of rabbits from anesthesia. Application of assigned treatments was continued every 12 hours for 7 days, and rabbits were anesthetized for BAER testing on day 8. Rabbits were euthanized, and samples were collected for histologic (6 ears/treatment) and scanning electron microscopic (1 ear/treatment) examination. RESULTS Most hearing thresholds (11/12 ears) were subjectively increased after myringotomy, with BAER measurements ranging from 30 to 85 dB in both ears. All day 8 hearing thresholds exceeded baseline (premyringotomy) values; results ranged from 30 to 85 dB and 80 to > 95 dB (the upper test limit) in saline solution–treated and ESS-treated ears, respectively. All ESS-treated ears had heterophilic otitis externa, epithelial hyperplasia of the external ear canal, various degrees of mucoperiosteal edema, and periosteal new bone formation on histologic examination. Scanning electron microscopy revealed that most outer hair cells in the ESS-treated ear lacked stereocilia or were absent. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that ESS has ototoxic effects in the middle ear of rabbits. Further research is needed to confirm these findings. Myringotomized laboratory rabbits may be useful to study ototoxicity of drugs used in human medicine. - Otitis externa and otitis media are common in rabbits, particularly in lop breeds - Topical medications can be toxic when the tympanic membrane is ruptured - Topical antimicrobials in human studies – infections resolved faster than with systemic antibiotics, topical placebo and topical antiseptics - Myringotomy - saline instilled in middle ear on one side and ESS in the other - BAER test right before and right after myringotomy on Day 0 then again Day 8 - Euthanized for histo evaluation - Hearing thresholds increased in all rabbits on Day 8 🡪 ESS ear worse than saline ear - All 6 rabbits had evidence of ototoxic changes in the ESS treated ear -- Calcification observed in the external ear canal epithelium -- Periosteal new bone formation in the tympanic bulla -- Loss of outer hair cells in the organ of Corti - Diffusion of molecules across the round window - main mechanism for ototoxic compounds to access the inner ear and organ of Corti -- Round window prominent and large in animals and positioned to allow prolonged contact with a fluid placed in the middle ear -- Rodents having the thinnest round window membrane – may be more susceptible to ototoxicity -- Rabbit round window thickness not known Takeaway: ESS = ototoxic when applied to middle ear of rabbits after myringotomy.

Answer 56

Lippi, I., Perondi, F., Petrini, D., La Fortuna, M. C., Luci, G., Intorre, L., ... & Meucci, V. (2019). **Evaluation of glomerular filtration rate estimation by means of plasma clearance of iohexol in domestic rabbits (Oryctolagus cuniculus)**. American journal of veterinary research, 80(6), 525-532. Objective: To evaluate glomerular filtration rate (GFR) estimation by means of plasma clearance of iohexol (IOX) in domestic rabbits and to assess accuracy of limited-sampling models for GFR estimation. Procedures: Each rabbit received IOX (64.7 mg/kg [0.1 mL/kg], IV), and blood samples were collected at predetermined times before and after administration. Plasma IOX concentration was determined by high-performance liquid chromatography. The pharmacokinetics of IOX was determined by a noncompartmental method. For each rabbit, plasma clearance of IOX was determined by dividing the total IOX dose administered by the area under the concentration-time curve indexed to the subject’s body weight. The GFR estimated from the plasma IOX concentration at 6 sampling times (referent model) was compared with that estimated from the plasma IOX concentration at 5 (model A), 4 (model B), and 3 (models C, D, and E) sampling times (limited-sampling models). Results: Mean ± SD GFR was 4.41 ± 1.10 mL/min/kg for the referent model and did not differ significantly from the GFR estimated by any of the limited-sampling models. The GFR bias magnitude relative to the referent model was smallest for model D in which GFR was estimated from plasma IOX concentrations at 5, 15, and 90 minutes after IOX administration. ● Model D – 5, 15, 90 min after administration of IOX. Conclusions and Clinical Relevance: Results suggested that plasma clearance of IOX was a safe, reliable, accurate, and clinically feasible method to estimate GFR in domestic rabbits. Further research is necessary to refine the method. ● Chronic kidney disease in rabbits – In dogs/cats with reduction in renal function, remaining glomeruli enter state of hyperfiltration; rabbits recruit silent (inactive) glomeruli. ● Rabbits with CKD can live for years without CS. ● Once loss of > 50-70% function, increased Cr and BUN. Can be impacted by extra-renal factors. ● GFR – Determined by urinary or plasma Cl (clearance) of an ideal filtration marker (freely filtered), not reabsorbed or secreted, not metabolized or bound, not nephrotoxic. ● Universally considered best indicator of overall renal function in human and veterinary medicine. ● Ioxehol – Nonionic, low-osmolarity contrast medium, low toxicity. Takeaway: ● Iohexol was well tolerated, safe at these doses in rabbits. ● Small data set technically not up to par with Am Soc of Vet Clin Path.

Answer 57

Tsouloufi, T. K., Tsakmakidis, I. A., Tsousis, G., Papaioannou, N., Tzika, E., & Kritsepi-Konstantinou, M. (2018). **Effect of subchronic oral exposure to zearalenone on the reproductive system of rabbit bucks**. American journal of veterinary research, 79(6), 674-681. OBJECTIVE: To determine the effect of subchronic oral exposure to zearalenone (ZEA) at a daily dose of 50 μg of ZEA/kg of body weight (an environmentally relevant concentration) on the reproductive system of rabbit bucks. ANIMALS: 8 healthy sexually mature New Zealand White rabbits. PROCEDURES: During the experimental period (March to June), each rabbit underwent a 7-week control protocol and then a 7-week treatment protocol. Water (0.5 mL) or ZEA solution (50 μg/kg [0.5 mL]) was administered orally once daily during the control and treatment period, respectively; ejaculates were collected weekly. Studied end points included semen quality variables (spermatozoa kinetics, morphology, viability, and DNA fragmentation), serum testosterone concentration, and results of histologic examination of the testes and epididymides following euthanasia at the end of the experimental period. RESULTS: Treatment with ZEA solution resulted in significant increases in spermatozoa beat-cross frequency, in the percentages of spermatozoa with head and midpiece abnormalities, and in the percentages of DNA-fragmented spermatozoa, compared with effects of the control treatment. Serum testosterone concentration, other spermatozoa velocity variables, and percentages of progressive and total motility, rapidly or slowly moving spermatozoa, and live spermatozoa did not differ significantly between the 2 periods. Histologic examination revealed no patterns of abnormal findings in the testes and epididymides. CONCLUSIONS AND CLINICAL RELEVANCE: Oral treatment with ZEA solution at an environmentally relevant con-centration caused minor interference with rabbit bucks’ sperm quality. Although mostly considered mild, the sperm quality changes warrant further investigation in terms of fertilizing capacity impairment. ● Zearalenone – nonsteroidal estrogenic mycotoxin produced by Fusarium – commonly found in cereals & grains ● Considered genotoxic, hematotoxic, nephrotoxic, and immunotoxic – swine are very susceptible ● Effects in female farm animals well documented, less so in males ● Rats, young boars (mature boars & rams not affected)– decreased spermatogenesis, testes weight, libido, and testosterone ● Zearalenone in rabbit bucks had no observed effect in testeosterone or semen quality ● The only increase was in % of sperm with fragmented DNA Take Home: ● Zearalenone produces mild changes in male rabbit spermatozoa quality, but is unlikely to affect their overall fertility

Answer 58

AJVR 2021 82(2):118-124 **Safety and efficacy of cold atmospheric plasma for the sterilization of a Pasteurella multocida-contaminated subcutaneously implanted foreign body in rabbits** Avellar HK, Williams MR, Brandão J, et al ABSTRACT: Objective: To determine whether a stainless steel implant sterilized with a novel cold atmospheric plasma sterilization (CAPS) device adversely affects local tissues in rabbits and whether CAPS was as effective as steam sterilization with an autoclave to inactivate Pasteurella multocida. Animals: 31 healthy New Zealand White rabbits. Procedures: Steam-autoclaved stainless steel implants inoculated with P multocida underwent a second steam autoclave sterilization (AIA) or CAPS (AICAPS). One AIA implant and 3 AICAPS implants were randomly placed subcutaneously at 4 sites in 21 rabbits (84 implants). These rabbits were monitored daily for 5 days for evidence of systemic illness and local tissue reactions at the implantation sites and then euthanized. Samples were taken from each implant site for bacterial culture and histologic examination. Results: Cultures of samples obtained from all sites were negative for bacterial growth. No significant difference was observed in mean skin thickness or erythema between AIA and AICAPS implant sites on any observed day. Also, individual histologic grades for the epidermis, dermis, subcutis, and muscle and total histologic grade were not significantly different between AIA and AICAPS implant sites. Conclusions and clinical relevance: Cold atmospheric plasma sterilization was noninferior to steam sterilization of P multocida-contaminated stainless steel implants in the rabbits in the present study. However, studies of the efficacy of CAPS for inactivation of other important bacteria are needed. Background: - Steam sterilization w/ an autoclave = most dependable method for surgical equipment - However, many devices and equipment cannot withstand high temperatures - Chemical gas sterilization is often used as an alternative - However, this method has safety and environmental concerns - Cold atmospheric plasma sterilization (CAPS) - Uses partially ionized gas (cold plasma) at room temp and atmospheric pressure - Produces UV light, charged particles, and RONS (reactive oxygen and nitrogen species) - These elements cause rapid destruction of microbial pathogens - Return to stable, harmless states when plasma is not being energize - A novel CAPS device has been developed (PZ100 air plasma sterilizer) - Only requires air and electricity to function - Has a shorter cycle time and lower cost than a conventional steam autoclave - Device is compact and portable such that it can be used in field settings Key Points: - Study supports CAPS is as effective as steam sterilization for stainless steel devices contaminated with P multocida implanted in rabbits - Negative bacterial culture results for all implantation sites for both methods - Inflammatory response following implantation procedure seen with both methods - Histopathology scores were not significantly different between methods - Efficacy of CAPS only determined for implants contaminated w/ P multocida - Other potential pathogens may cause surgical site infections TLDR: Cold atmospheric plasma sterilization was noninferior to steam sterilization of P multocida-contaminated stainless steel implants in the rabbits

Answer 59

Journal of the American Veterinary Medical Association 259(10): 1148-1153, 2021 **ASSESSMENT OF INTRAMUSCULAR ADMINISTRATION OF THREE DOSES OF ALFAXALONE COMBINED WITH HYDROMORPHONE AND DEXMEDETOMIDINE FOR ENDOSCOPIC-GUIDED OROTRACHEAL INTUBATION IN DOMESTIC RABBITS (ORYCTOLAGUS CUNICULUS)** Stephanie N. Reabel, Patricia Queiroz-Williams, Jeannette Cremer, Chiara E. Hampton, Chin-Chi Liu, Anderson da Cunha, Javier G. Nevarez Abstract OBJECTIVE To determine the dose of alfaxalone for IM administration combined with dexmedetomidine and hydromorphone that would allow endoscopic-guided orotracheal intubation in rabbits without causing a decrease in respiratory rate or apnea. ANIMALS 15 sexually intact (9 females and 6 males) healthy Miniature Lop rabbits weighing a mean ± SD of 2.3 ± 0.3 kg and ranging in age from 4 to 9 months. PROCEDURES In a randomized, controlled clinical trial, **rabbits received 0.1 mg of hydromorphone/kg and 0.005 mg of dexmedetomidine/kg, plus alfaxalone at either 2 mg/kg (5 rabbits), 5 mg/kg (5 rabbits), or 7 mg/kg (5 rabbits)**. Drugs were mixed in a single syringe and administered IM. Semiquantitative rating scales were used to evaluate quality of anesthesia and intubation. Orotracheal intubation was attempted with endoscopy and confirmed by capnography. RESULTS The number of successful intubations was 0, 3, and 4 in rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. Median (range) anesthesia quality scores (scale, 0 to 12; 12 = deepest anesthesia) were 3 (2 to 5), 6 (5 to 6), and 6 (4 to 9) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. The median (range) intubation quality scores (scale, 0 to 3 [ie, intubation not possible to easiest intubation]) were 0 (0 to 0), 2 (0 to 3), and 2 (0 to 3) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. None of the rabbits experienced a decrease in respiratory rate or apnea. CONCLUSIONS AND CLINICAL RELEVANCE Increasing doses of alfaxalone combined with hydromorphone and dexmedetomidine increased the success rate of endoscopic-guided orotracheal intubation. Increasing the dose of alfaxalone had no effect on respiratory rate. Key Points: - The onset of effects following IM administration of alfaxalone was smooth and rapid - Maximal sedative effects occurred within 10 minutes of injection - Lateral recumbency was achieved only with A7 vs. sternal recumbency with A2 and A5 - Jaw tone scores for rabbits with A5 and A7 were similar and higher than that of rabbits in A2 à sufficient muscle relaxation to open mouth for intubation More A7 rabbits were successfully intubated - All rabbits responded to toe pinch with a complete withdrawal of the forelimb à response to noxious stimulation was still present at all alfaxalone doses Versus other study that used higher dexmedetomidine Take-Home Message: - IM administration of alfaxalone in combination with hydromorphone and dexmedetomidine caused dose-dependent anesthetic induction of rabbits, facilitating endoscopic-guide orotracheal intubation with minimal changes in respiratory rate.

Answer 60

**Clinical and pathological findings in rabbits with cardiovascular disease: 59 cases (2001–2018)** Sarah Ozawa DVM1, David Sanchez-Migallon Guzman LV, MS2, Kevin Keel DVM, PhD3, and Catherine Gunther-Harrington DVM2 Abstract OBJECTIVE To determine epidemiological features of cardiovascular disease in rabbits examined at a veterinary teaching hospital and characterize clinical and pathological findings. ANIMALS 59 rabbits. PROCEDURES Medical records from 2001 to 2018 were reviewed, and data were collected. Echocardiographic images and histologic diagnoses were reviewed. RESULTS The prevalence of cardiovascular disease was 2.6% (59/2,249). Clinical signs related to cardiac disease included heart murmur (n = 25 rabbits), arrhythmia (22), tachypnea or dyspnea (13), hyporexia or anorexia (13), and muscle wasting (9). Radiographic (n = 39) abnormalities included cardiomegaly (19) and peritoneal (12) and pleural (11) effusion. Common echocardiographic (n = 37) diagnoses included degenerative valve disease (15), dilated cardiomyopathy (7), unclassified cardiomyopathy (4), restrictive cardiomyopathy (3), and hypertrophic cardiomyopathy (2). On ECG (n = 19), supraventricular arrhythmias (16) were more common than ventricular arrhythmias (12). Thirty-five necropsy reports were available, and diagnoses included cardiomyopathy (n = 14), myocarditis (10), and arteriosclerosis (9). Medical management (n = 20) included a wide range of drugs and dosages with few adverse effects. Survival times (n = 36 rabbits) ranged from 1 to 2,353 days with a median cardiac disease–specific survival time of 306 days. CONCLUSIONS AND CLINICAL RELEVANCE The findings provided information on the prevalence of cardiovascular disease in rabbits and survival times for affected rabbits. Right-sided, left-sided, and biventricular congestive heart failure occurred equally. Median survival time was lower than that reported for other species. Further research on the diagnosis and treatment of cardiovascular disease in rabbits is needed. Key Points: - -

Answer 61

Clinical, surgical, and pathological findings in client-owned rabbits with histologically confirmed appendicitis: 19 cases (2015–2019) JAVMA 2021 260(1) 82-93 Abstract: OBJECTIVE To report clinical, surgical, and pathological findings in client-owned rabbits with histologically confirmed appendicitis. ANIMALS 19 rabbits. PROCEDURES Medical records for client-owned rabbits that had a histologic diagnosis of appendicitis were reviewed. RESULTS Median age of the rabbits at presentation was 24.0 months (range, 4 to 84 months). Seventeen cases occurred during the summer and fall seasons. Decreased appetite (17/19 rabbits), abnormal rectal temperature (hyperthermia, 9/16 rabbits; hypothermia, 4/16 rabbits), hypocalcemia (8/11 rabbits), and hypoglycemia (7/15 rabbits) were common signs. Abdominal ultrasonography and CT findings were suggestive of appendicitis in 6 of 8 rabbits and in 1 of 2 rabbits, respectively. Of the 6 rabbits that received medical treatment, 3 died at 48 hours, 1 died at 24 hours after hospitalization, and 1 died at 10 days after presentation; 1 rabbit was alive at 1,030 days after presentation. Of the 8 rabbits that underwent appendectomy, 3 died before discharge from the hospital and 1 died 113 days after surgery; 4 rabbits were alive at 315, 334, 1,433, and 1,473 days after presentation. The remaining 5 rabbits either died or were euthanized before treatment could be instituted. In each of the 19 rabbits, the appendix had evidence of severe inflammation with mucosal ulceration, heterophilic inflammation, and necrotic debris. CLINICAL RELEVANCE For rabbits with decreased appetite and an apparently painful abdomen, hyperthermia, hypocalcemia, or hypoglycemia, appendicitis should be considered as a differential diagnosis. Further comparisons of medical and surgical treatments are required to establish treatment recommendations for rabbits with appendicitis. Rabbit GI anatomy * distinct vermiform appendix at apex of the cecum * Present in few other sp → humans and some other primates, other lagomorphs, wombats, few rodents such as Cape dune mole-rats * Identification: distinct decrease in diameter, change in tissue color, lack of spiral muscular bands typical of cecum * important for development of immune function - contribution occurs mostly early after birth, with a 99% reduction of B lymphopoiesis by 16 weeks of age and no evidence of progenitor B cells in appendix of adult rabbits Results and Discussion: * 21 cases of appendicitis * Common CS: GI stasis and lethargy, acute and intermittent * most common hematologic alteration - anemia * most common biochem alterations - hypocalcemia and hypoglycemia * Rads - no specific findings * US - abnormal appendix (n = 6), lymphadenomegaly (3), focal hyperechoic peritoneum (2), free fluid in the abdomen (2), thickening of wall of sacculus rotundus (1), presumed intestinal mass (1), hepatomegaly (1) * increased thickness of appendix wall, loss of typical multilayered structure of appendix wall, increased overall diameter of appendix, presence of fluid or mucoid content rather than alimentary content in appendix * Seasonality - all but 2 cases occurred in summer and fall * More common in summer in humans * median age of presentation - 2 years, appendicitis could be more common in young rabbits * Possibly suggestive PE findings - high rectal temperature (n=9), palpation of a tubular abdominal mass, and signs of discomfort during abdominal palpation o most rabbits had clinical signs for < 48 hours or no clinical signs, 2 rabbits had intermittent clinical signs for 29 and 89 days * Surgical management o ileocecal fold -short mesenteric ligament that connects ileum to appendix in rabbits o ileocecal fold - infiltrated by number of small, short vessels o to isolate appendix from remainder of intestinal tract in a rabbit, ileocecal fold has to be excised - radiosurgery recommended o ligation of the appendix in 8 rabbits was performed with 1 of 2 approaches: o circumferential ligation of appendix at its point of origin in cecum, followed by placement of an intestinal clamp distal to the sutures and subsequent excision of the appendix o excision of appendix after placement of intestinal clamps or application of digital pressure by an assistant at base of the appendix, followed by closure of cecum with simple interrupted sutures * Found in many rabbits with appendicitis - mucosal ulceration, heterophilic inflammation, and lymphoid follicle necrosis and abscess formation of appendix

Answer 62

AJVR 2022, 83(12) **A NOVEL VACCINE CANDIDATE AGAINST RABBIT HEMORRHAGIC DISEASE VIRUS 2 (RHDV2) CONFERS PROTECTION IN DOMESTIC RABBITS** Angela M. Bosco-Lauth, DVM, PhD1; Bethany Cominsky, BS1; Stephanie Porter, DVM, MHS2; J. Jeffrey Root, PhD2; Amber Schueler, BS3; Gary Anderson, DVM, MS, PhD3; Sara VanderWal, BS3; Andy Benson, BS3 – rev by AJC OBJECTIVE: To evaluate efficacy of a novel vaccine against rabbit hemorrhagic disease virus 2 (RHDV2) in domestic rabbits. ANIMALS: 40 New Zealand White rabbits obtained from a commercial breeder. PROCEDURES: Rabbits were vaccinated and held at the production facility for the duration of the vaccination phase and transferred to Colorado State University for challenge with RHDV2. Rabbits were challenged with oral suspensions containing infectious virus and monitored for clinical disease for up to 10 days. Rabbits that died or were euthanized following infection were necropsied, and livers were evaluated for viral RNA via RT-PCR. RESULTS: None of the vaccinated animals (0/9) exhibited clinical disease or mortality following infection with RHDV2 while 9/13 (69%) of the control animals succumbed to lethal disease following infection. CLINICAL RELEVANCE: The novel vaccine described herein provided complete protection against lethal infection following RHDV2 challenge. Outside of emergency use, there are currently no licensed vaccines against RHDV2 on the market in the United States; as such, this vaccine candidate would provide an option for control of this disease now that RHDV2 has become established in North America. Key Points: - Rabbit hemorrhagic disease virus 2 (RHDV Lagovirus G1.2) – calicivirus of Lagovirus genus -- RHDV2 is an RNA virus with wider host range than classic RHDV (European and other hares, wild native NA rabbits within genus Sylvilagus) -- Young (< 8 wk) and wild NA lagomorphs resistant to RHDV but not RHDV2 -- Both RHDV and RHDV2 are highly pathogenic in domestic rabbits – mortality 70-100% within 2 to 3 days of exposure -- Spread via direct contact/contact with infectious secretions (including feces) or mechanical vectors. Cottontails susceptible but may recover and serve to spread infection. -- Viruses hardy in the environment and no cross protection between RHDV and RHDV 2 -- Europe → 2 inactivated commercial vaccines for RHDV2 - Objective – evaluate of novel vaccine (inactivated recombinant subunit vaccine) against RHDV2 produced by US organization with intent to license and manufacture -- Vaccinated SQ then boostered 3 weeks later. Challenged at day 28. -- Livers tested via PCR - ~70% from placebo group died/euthanized following RHDV2 infection versus 0% of vaccinated rabbits -- Quantity of virus in liver lower in survivors than animals that died from RHDV infection -- Nearly all rabbits with RHDV2 disease were febrile (> 105F) in the days preceding death -- 3/9 vaccinated rabbits developed fever 1-3 days post infection -- Vaccinated animals retained viral RNS in tissues after infection Take home: - Vaccine was 100% effective at preventing mortality while 70% of unvaccinated animals died following exposure to infection. - 3/9 vaccinated animals developed transient fevers after infection.

Answer 63

AJVR 2022 83(7):ajvr.21.11.0177 **Pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus)** Gardhouse S, Kleinhenz M, Hocker SE, Weeder M, Montgomery SR, Zhang Y, Porting A, Rooney T ABSTRACT: OBJECTIVE: To examine the pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS: 6 healthy New Zealand White rabbits. PROCEDURES: Pharmacokinetics were determined from plasma concentrations measured via ultra performance liquid chromatography-tandem mass spectrometry after oral administration of firocoxib at a dose of 3.74 to 4.20 mg/kg. Pharmacokinetic analysis was performed using non compartmental methods. Pharmacodynamics of firocoxib were evaluated by measuring plasma concentrations of thromboxane and prostaglandin via ELISAs as surrogate markers of cyclooxygenase enzyme isoform inhibition. RESULTS: The terminal rate constant was 0.07 hours (range, 0.05 to 0.11 h). The mean maximum concentration (Cmax) and time to Cmax were 0.16 µg/mL and 3.81 hours (range, 2.0 to 8.0 h), respectively. Mean residence time was 15.02 hours. Mean elimination half-life was 9.12 hours. For the pharmacodynamic analysis, firocoxib administration did not demonstrate a significant difference between any time point for prostaglandin E2 and only a significant difference between 24 and 48 hours for thromboxane B2. CLINICAL RELEVANCE: Although the pharmacokinetic research supports that plasma firocoxib concentrations that would be therapeutic in dogs are achieved in rabbits, the pharmacodynamic results do not demonstrate a significant difference in levels of cyclooxygenase-2 inhibition, which indirectly reflects the anti-inflammatory effects of the drug. Further pharmacodynamic studies and multidose studies are warranted to determine the efficacy and safety of this drug in rabbits. Key Points: - COX-1 expressed in many tissues, produces cytoprotective prostaglandins critical for: -- Maintenance of the gastric mucosa -- Renal blood flow and GFR -- Production of precursors for thromboxane synthesis (inducer of platelet aggregation) - COX-2 inducible enzyme, produces proinflammatory prostaglandins -- Plays a major role in inflammation and neoplasia -- COX-2 selective inhibitors have been demonstrated to have fewer side effects - Thromboxane B2 & PGE2 = surrogate markers of COX-1 and COX-2 inhibition, respectively - Rabbits appear to tolerate NSAIDs well with minimal side effects reported -- Single report of gastric ulceration in a rabbit that received chronic meloxicam -- In dogs, COX-2 inhibition therapeutic plasma concentrations = 30 to 67 ng/mL -- This level was achieved between 0.5-2.0 hours in this study and maintained for 24 hours **TLDR: 4 mg/kg firocoxib achieved therapeutic plasma levels for analgesia but pharmacodynamic results did not demonstrate a significant difference in levels of COX-2 inhibition**

Answer 64

AJVR 2022 83(10) online **Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus)**. OBJECTIVE To determine the pharmacokinetics of a solution containing cannabidiol (CBD) and cannabidiolic acid (CBDA), administered orally in 2 single-dose studies (with and without food), in the domestic rabbit (Oryctolagus cuniculus). ANIMALS 6 healthy New Zealand White rabbits. PROCEDURES In phase 1, 6 rabbits were administered 15 mg/kg CBD with 16.4 mg/kg CBDA orally in hemp oil. In phase 2, 6 rabbits were administered the same dose orally in hemp oil followed by a food slurry. Blood samples were collected for 24 hours to determine the pharmacokinetics of CBD and CBDA. Quantification of plasma CBD and CBDA concentrations was determined using a validated liquid chromatography–mass spectrometry (LC-MS) assay. Pharmacokinetics were determined using noncompartmental analysis. RESULTS For CBD, the area under the curve extrapolated to infinity (AUC)0–∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC0–∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively. Adverse effects were not observed in any rabbit. CLINICAL RELEVANCE CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater Cmax but had a shorter t1/2λ than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit. Key Points: * Endocannabinoid system plays a role in analgesic and inflammatory pathways across species * Cannabidiol (CBD) m cannabidiolic acid (CBDA) and tetrahydrocannabinol (THC) are plant derived * Lack of studies characterizing PK and appropriate dosing, despite many owners already using CBD products to treat pain in their pets * No differences in serum biochemistry panels before and after treatment * No adverse effects * Both CBD and CBDA had longer plasma concentrations and half lives when administered without food, vs admin with a food slurry Take home message: This study provides the PK of CBD and CBDA in rabbits, for oral dosing. Both are better absorbed without food.

Answer 65

AVMA 2022 260(11) 1334-1342 **Clinicopathological findings in and prognostic factors for domestic rabbits with liver lobe torsion - 82 cases (2010–2020)** OBJECTIVE To document clinicopathologic findings in domestic rabbits with liver lobe torsion and identify prognostic factors. ANIMALS 82 rabbits. PROCEDURE Medical records of 4 institutions were reviewed to identify rabbits with an antemortem diagnosis of liver lobe torsion that were examined between 2010 and 2020. RESULTS The prevalence of liver lobe torsion was 0.7% (82/11,402). In all 82 rabbits, the diagnosis was made by means of abdominal ultrasonography. Fifty (60.1%) rabbits underwent liver lobectomy, 23 (28%) received medical treatment alone, and 9 (10.9%) were euthanized or died on presentation. Overall, 32 (39%) rabbits died within 7 days of initial presentation and 50 (61%) survived. Seven-day survival rate did not differ significantly between medical treatment alone and surgical treatment. However, median survival time following medical treatment (530 days) was shorter than that following surgical treatment (1,452 days). Six of 14 rabbits had evidence of systemic inflammatory disease on necropsy. Rabbits with right liver lobe torsion were less likely to survive for 7 days than were those with caudate torsions (P = 0.046; OR, 3.27; 95% CI, 1.04 to 11.3). Rabbits with moderate to severe anemia were less likely to survive for 7 days than were rabbits that were not anemic or had mild anemia (P = 0.006; OR, 4.41; 95% CI, 1.55 to 12.51). Other factors associated with a decreased 7-day survival rate were high heart rate at admission (P = 0.013) and additional days without defecation after admission (P < 0.001). Use of tramadol was associated with an increased survival rate (P = 0.018). CLINICAL RELEVANCE The prognosis for rabbits with liver lobe torsions was more guarded than previously described. Rabbits that underwent liver lobectomy had a longer median survival time than did rabbits that only received medical treatment. Key Points: - Median age was 3 years - Holland Lop was the most common breed, followed by misc Lop and French Lop - Most common clinical signs were hypo/anorexia > lethargy > decreased defecation; 1/3rd had a previous history of GI stasis -- ¼ of rabbits were hypothermic -- ½ of rabbits described as having quiet mentation. 30% had cranial abdominal pain, 30% had decreased gut sounds. Palpable abdominal mass in 15%. -- Anemia in 60% of rabbits. Thrombocytopenia also common. **Severity of anemia influenced 7-day survival, with moderate to severe anemias less likely to survive for 7 days vs those with mild or no anemia**. -- Chemistry: 77.5% azotemia (BUN), elevated AST (95%), ALP (41%) -- Peritoneal effusion was common (77%), but hemorrhagic effusion was uncommon - ¾ of rabbits had free fluid on ultrasound, more often anechoic - Caudate lobe affected in 74%, right liver lobe in 20% - necropsy : hepatic necrosis #1, followed by hepatic congestion; additional hepatic lesions in other lobes were seen in many rabbits, which was surprising - Outcome -- 40% died or were euthanized w/in 7 days after presentation, odds of survival decreased with each addl day not defecating, higher HR -- Use of tramadol improved survival time -- Perianesthetic mortality rate was 17% -- Survival with surgery 72%, medical management 60% Take home message - Anemia, thrombocytopenia, elevated liver enzymes, azotemia are common findings in rabbits with liver lobe torsion. - Caudate lobe affected most - Surgical management improved survival time over medical management - Tramadol use was the only medical tx associated with improved survival - **Rabbits with higher HRs, increasing # of days w/o defecation, right liver lobe torsion, and moderate to severe anemia were less likely to survive**

Answer 66

JAVMA 2022 260(12):1-5 **Stabilization of a vertebral fracture by a monolateral external fixator placed percutaneously with fluoroscopy guidance in a rabbit (Oryctolagus cuniculus**) Rosas-Navarro J, Paoletti C, Quinton JF, Rossetti D ABSTRACT: CASE DESCRIPTION A 2-year-old intact male Mini Lop rabbit (Oryctolagus cuniculus) exhibited acute paraplegia and was suspected of having a traumatic spinal injury after leaping from the owner’s arms. CLINICAL FINDINGS In the physical examination, the patient was conscious and responsive and presented a loss of hind-limb motor function. The results of the neurologic examination indicated a T3-L3 spinal cord lesion. Vertebral column radiography and CT showed a fracture of the dorsal arch in the right caudal part of vertebra L1 and a fracture of the caudal end plate of vertebra L1 without displacement. TREATMENT AND OUTCOME The vertebral fracture was stabilized by a monolateral external fixator placed percutaneously with fluoroscopy guidance. The rabbit was discharged 48 hours after surgery. Three days later, the rabbit was able to walk with mild paraparesis, and 2 weeks after surgery, the rabbit showed full recovery of neurologic function. The follow-up performed 6 weeks after surgery showed normal gait, good alignment and complete consolidation of the fracture. The external fixator was then removed. The follow-up examination and radiographic findings showed complete recovery at 2 and 6 months after surgery. CLINICAL RELEVANCE The most common cause of traumatic posterior paralysis in rabbits is vertebral fracture. This article describes the possibility and successful outcome of stabilizing a vertebral fracture in a rabbit with an external fixator using a minimally invasive fluoroscopic technique. This technique, described to the authors’ knowledge for the first time in a rabbit, allows a fracture to be stabilized accurately without any incisions while minimizing complications and postoperative pain. Background: - Rabbits have a haversian bone structure; however, cortical bone is thinner than in dogs or cats - CT = imaging modality of choice for osseous lesions in patients with spinal cord injury -- MRI is preferred over CT for evaluating soft tissue injuries such as spinal cord injuries (spinal cord edema and myelomalacia), but osseous details are poorly displayed -- In dogs, radiography has only moderate sensitivity for fractures and luxation (~75%) -- Poor at detecting fractures in the middle and dorsal vertebral compartments - In dogs and cats, indications for surgical intervention include compressive or unstable lesions - Thoracic or lumbar vertebral injuries have a good prognosis when nociception is intact - A large-scale prospective study found perianesthetic mortality rate rabbits = 1.39% -- 5x higher than that found in dogs and cats Key Points: - Surgeons utilized fluoroscopically guided percutaneous placement of pins for spinal stabilization -- This technique provides accurate visualization of vertebral bodies, allowing precise control over pin placement and better reduction -- Compared with open surgical approaches, decreases the amount of tissue dissection needed and lessens the degree of uncertainty involved in placing pins -- Decreases the occurrence of postoperative complications and morbidities and allows for an earlier recovery of function than similar open surgery approaches - In dogs, the main pitfalls of external fixation are implant breakage, pin tract inflammation or infection and the need for specialized postoperative care TLDR: First report of successful outcome of a surgical repair of a vertebral fracture in a rabbit

Answer 67

JAVMA 2022 260(15):1934-1940 **Tympanic bullae ultrasonography is feasible in nonsedated healthy rabbits (Oryctolagus cuniculus)** Coeuriot CTN, Guise L, Cazin CC, Meregalli R, Fusellier MS ABSTRACT: Objective: To assess the feasibility of ultrasonography of the tympanic bullae (TB) in live, nonsedated rabbits (Oryctolagus cuniculus). Animals: 40 healthy rabbits undergoing TB ultrasonography without sedation between September 2021 and May 2022. Procedures: For each rabbit, fur was clipped over an area (3 X 3 cm) at the level of the angular process of each mandible, then 3 ultrasonographic planes of each TB were imaged via ventral approach, with measurement of the time taken to complete the examination. Three items were assessed for each plane: TB depth, wall integrity, and contents (present or absent). Results were compared for rabbits grouped as standard-sized breed type versus dwarf-sized breed type. Results: The examination could be carried out successfully in 36 of 40 (90%) of rabbits with clipping. The restraint and examination were relatively well tolerated by the animals, except for the transverse sections. Obtaining oblique and longitudinal sections, carried out on 33 of 40 (83%) rabbits in our study, allowed for evaluation of the TB. The examination was feasible with all rabbit sizes. The depth of the TB was found to be linked to the size of the rabbit and especially to the size of its jaw. Visualization of the distal bulla wall was observed in 2 of the 40 (5%) subjects, consistent with abnormal fluid contents or bulla osteitis. Clinical relevance: Ultrasonography of the TB was easy to learn and rapid to perform, with a mean examination time of < 10 minutes (mean of 8.71 minutes) without any sedation. Key Points: - High frequency of subclinical otitis media in rabbits - CT or MRI is the gold standard to assess the integrity of the tympanic bullae -- US has been used successfully to image in other species - Depth of tympanic bullae is linked to the size of the rabbit, especially the size of its jaw - US required a small probe and high frequency (better resolution at shallow depth) - Study allowed the identification, or at least suspicion, of otitis media in 2 rabbits TLDR: US of the tympanic bullae was easy to learn, rapid to perform, and didn’t require sedation Useful Figure: Image of the ventral view of a skull from a clinically normal adult rabbit (Oryctolagus cuniculus) displaying the longitudinal section (LS), oblique section (OS), and transverse section (TS), corresponding with the ultrasonographic planes imaged of the right (R) and left (L) tympanic bullae (TB)

Answer 68

**Clinical and pathological findings of rabbits with lymphoma: 16 cases (1996–2019)**. Robertson JA, Guzman DS, Willcox JL, Keel K, Vernau W. Journal of the American Veterinary Medical Association. 2022;260(9):online. OBJECTIVE To determine the clinical and pathological findings of rabbits diagnosed with lymphoma. ANIMALS 16 rabbits. PROCEDURES The medical and pathology records database of the Veterinary Medical Teaching Hospital at the University of California, Davis was searched for rabbits diagnosed with lymphoma from 1996 to 2019. RESULTS Mean age of the 16 rabbits was 8 years (range, 4.5 to 12 years). Immunophenotyping was performed in 14 cases. Diffuse, large, B-cell lymphoma was most common (n = 7) followed by epitheliotropic, T-cell lymphoma (2); type II enteropathy-associated, T-cell lymphoma (2); marginal-zone, B-cell lymphoma (1); peripheral, T-cell lymphoma not otherwise specified (cutaneous nonepitheliotropic lymphoma; 1); primary, mediastinal (thymic) large B-cell lymphoma (1), and unclassified (cytology only with no immunophenotyping; 2). Multiple chemotherapy protocols were used on the basis of each individual animal’s disease state. Initial clinical improvement was reported for most rabbits receiving chemotherapy (5/6), with diffuse B-cell lymphoma responding most favorably to treatment. The 11 rabbits included in the survival analysis had a median survival time of 60 days (range, 1 to 480 days), and those diagnosed with B- and T-cell lymphoma had a median survival time of 8 and 36 days (range, 1 to 150 and 1 to 90 days), respectively. CLINICAL RELEVANCE Rabbits develop a range of lymphoma subtypes and, similar to humans and dogs, diffuse large B-cell lymphoma appears to be the most common. Chemotherapy treatments followed multiple protocols, which were mostly well tolerated and had a highly variable response. Further research into chemotherapy protocols is needed to optimize treatment of lymphoma in rabbits. Background - Lymphoid malignancy - second most common type of neoplasia in domestic rabbits -- Most frequently reported neoplasm of young or juvenile rabbits, majority <2 yo at diagnosis -- Recent retrospective: 96% of rabbit lymphomas were B-cell -- Peripheral lymphadenopathy +/- organomegaly (liver, spleen, kidneys) -- Cutaneous nodules or plaques +/- ulcerations, crusts, erythema, alopecia -- Mediastinal disease - bilateral exophthalmia +- respiratory distress -- Often disseminated at the time of diagnosis Key Points - 16 cases - 9 B-cell, 5 T-cell, various presentations/locations -- Diffuse large B-cell lymphoma, epitheliotropic T-cell lymphoma, type II enteropathy-associated T-cell lymphoma, splenic marginal-zone B-cell lymphoma, peripheral T-cell lymphoma, cutaneous nonepitheliotropic lymphoma, thymic large B-cell lymphoma -- Diffuse large B-cell lymphoma most commonly diagnosed form (7/16 rabbits) -- Secondary leukemia in 3/8 cases with CBC’s - Cytology was diagnostic for large cell lymphoma in all rabbits sampled - Median survival time 60d, 8 days with B-cell, 36 days with T-cell, 90d in rabbits that were treated beyond supportive care. - Age range 4.5-12 yr, mean 8 yr - Thrombocytosis more common (other spp get thrombocytopenia), no paraneoplastic hypercalcemia in these cases - Cutaneous lymphoma CS: alopecia with hyperkeratosis, erythema, or palpable cutaneous masses affecting the entire body but more commonly at commissures of lips, ventrum, pelvic region, thoracic limbs Conclusions - “Rabbits develop a range of lymphoma subtypes and, similar to humans and dogs, diffuse large B-cell lymphoma appears to be the most common. Chemotherapy treatments followed multiple protocols, which were mostly well tolerated and had a highly variable response.”

Answer 69

JAVMA 2022 261(2):223-228 **Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial** Costa RS, Ciotti-McClallen M, Tilley R, et al ABSTRACT: Objective: To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). Animals: 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021. Procedures: **In this controlled clinical trial, rabbits were randomly assigned to receive alfaxalone (4 mg/kg, IM) alone (group A; n = 8) or with buprenorphine (0.03 mg/kg, IM; group BA; 8) or hydromorphone (0.1 mg/kg, IM; group HA; 8)**. Vital signs and sedation scores were recorded immediately prior to (T0) and 10 minutes after (T1) treatment. Ease of IV catheter placement and pain scores were also evaluated. **All rabbits received ketamine (2.5 mg/kg, IV), midazolam (0.13 mg/kg, IV), and meloxicam (0.5 mg/kg, SC) before orchiectomy but after IM treatments**. Results were compared across groups with ANOVA or Fisher exact tests and across time with paired t tests. Results: Sedation score, median time to recumbency, and ease of catheter placement did not differ among groups. Supraglottic airway device placement was possible for 1 rabbit in group A, 1 in group BA, and 2 in group HA. Mean respiratory rate at T1 versus T0 was significantly decreased for groups BA (63.8 vs 128.6 breaths/min) and HA (66.7 vs 123.2 breaths/min). **Mean postoperative pain scores were significantly lower for rabbits in group HA (0.58), compared with those in groups A (2.25) and BA (2.06)**. Clinical relevance: All 3 treatments provided reliable sedation; however, alfaxalone (4 mg/kg, IM) combined with hydromorphone (0.1 mg/kg, IM) may be a better choice for painful procedures. Key Points: - Rabbits are at a higher risk of anesthetic-related death (overall risk of 1.39%) -- In one study a 4.8% (10/210) mortality rate w/ in 72 hr post-anesthesia was reported -- Possible contributing factors include undiagnosed cardiovascular or respiratory diseases, challenges with IV catheterization and intubation, and physiologic responses to stress - Alfaxalone have gained popularity as an alternative for sedation and immobilization of rabbits -- Alfaxalone = rapid onset, short duration of action, minimal to mild cardiovascular effects - Ketamine administered IM is reported to be painful - Medetomidine-based protocols have a higher risk of laryngospasm and bradycardia - Buprenorphine = partial μ-opioid agonist w/ high affinity for µ receptor but only partial activity - Hydromorphone is a full μ-opioid receptor agonist used to treat moderate to severe pain Key Points - IM alfaxalone (4 mg/kg) alone or with buprenorphine (0.03 mg/kg) or hydromorphone (0.1 mg/kg) provided reliable sedation in healthy rabbits - Combination of alfaxalone w/ hydromorphone did not provide superior sedation but appeared to provide superior analgesia - No severe adverse events or mortality were observed in the rabbits included in this study -- No cardiac effects or apnea noted following all 3 IM treatments -- However, RR was significantly lower than baseline - Sedation score and time to lateral recumbency did not differ between treatment groups -- Most of the rabbits achieved lateral recumbency within 10 minutes -- No rabbits required additional sedation for IV catheter placement - IM treatments did not provide adequate depth for supraglottic airway device placement -- Higher doses may be needed (and volumes of drugs exceeding recommended 0.25 mL/kg) -- Resp & CV depression may be more profound w/ higher doses of alfaxalone - Postoperative pain scores were lower in rabbits treated IM with hydromorphone and alfaxalone TLDR: All 3 treatments provided reliable sedation; however, alfaxalone (4 mg/kg, IM) combined with hydromorphone (0.1 mg/kg, IM) may be a better choice for painful procedures

Answer 70

Fowler 10 Chapter 25: Rabbit Hemorrhagic Viral Disease and its Effects on Wildlife Background - Nonenveloped, single stranded RNA virus- Calicivirus -- RHDV -- RHDV2 -- EBHSV (european brown hare syndrome virus) - RHDV and EBHSV are endemic in Europe -- Australia used RHDV as a biological control agent to reduce environmental and agricultural damage from introduced European rabbits-> but escaped containment and caused widespread mortalities across Australia within 2 years - Initial RHDV2 in North America was Quebec -- Sporadic outbreaks then happened in Ohio, Washington and New York -- Then confirmed in domestic and native wild leporids in New Mexico -- Isolation and genome evaluation suggest that the RHDV2 in New York compared to Southern states were from separate introductions Species Susceptibility and Transmission Dynamics - RHDV= European rabbit - EBHSV= European Hares - RHDV2= infection of many leporids - Unknown if pikas are susceptible - Transmission= oral, nasal or conjunctival routes or skin trauma, urine, feces, and respiratory secretions -- Rabbits may shed the virus for 30 days after recovery (RHDV) -- Virus survives heat/freezing -- Readily spreads on fomites -- Predators and scavengers may be mechanical vectors: with nucleic acids of RHDV and EBHSV found in feces of various carnivores -- Impacts of RHDV is greater in arid regions compared to cooler, humid areas Clinical Disease Manifestation and Diagnosis - Incubation period and time to death for RHDV and EBHSV is short - RHDV2 has a slightly longer incubation period - Young animals seem resistant to RHDV and EBHSV - Peracute disease= sudden death without clinical signs - Acute disease= anorexia, apathy, conjunctival congestion, neurologic signs, respiratory signs, foamy or bloody discharge, lacrimation, ocular hemorrhage and epistaxis - Subacute disease=signs are milder, and survivors develop antibodies - Chronic= anorexia, lethargy and jaundice precede death by 1-3 weeks - DDx: tularemia, septicemic pasteurellosis, atypical myxomatosis, enterotoxemia, plague, anticoagulant rodenticides, heat exhaustion, trauma or other cause of severe septicemia with secondary DIC - Treatment= supportive care - Primary tissues= liver, lung, spleen -- Virus replication in liver within first hours of infection= necrotic and apoptotic cell death of hepatocytes -- Acute necrotizing hepatitis and DIC with multiple organ failure -- Animals= good body condition and have blood in nares or reddened conjunctiva - Gross lesions= hepato/splenomegaly, hepatic pallor or congestion (may have mild reticular pattern), hyperemia, pulmonary congestion, and hemorrhages in multiple organs - Histo= acute hepatic necrosis, pulmonary congestion, hemorrhages and fibrin microthrombi in capillaries - Diagnostic test of choice= RT-PCR (liver being preferred sample) - Serologic detection of antibodies can be doe with ELISA or HI - Iso-ELISA= provide titers for IgA, IgM, and IgG - Reportable Control and Prevention - Effective ingredients = potassium peroxymonosulfate, sodium hypochlorite (bleach diluted with water 1:10), accelerated hydrogen peroxide (Rescue), Alkaline phenolic germicidal detergent - Disease eradication is not feasible so efforts should be made toward reduced anthropogenic spread and controlling disease in domestic rabbits - Strict biosecurity: sanitation, disinfection and quarantine - Field necropsies SHOULD NOT BE PERFORMED (ddx tularemia and plaque)- whole carcasses double bagged and transported to Biologic Safety Level2 or higher containment lab - Vaccination has been employed for domestic rabbits, captive wild rabbits, and endangered species (vx to specific strain or combined is needed due to no crossover protection between RHDV/RHDV2) - Precautions for outdoor recreationists, falconers, and hunters Impacts to Wildlife and Ecosystems - European rabbit= valuable game animal and keystone prey species is severely affected (also by habitat loss and myxomatosis) -- Endangered Iberian lynx and Spanish Imperial Eagles depend on this rabbit for prey - In North America- unknown- bobcats and golden eagles need to be monitored as their population could be affected as rabbits die off -- Cottontails and jackrabbits have already declined in numbers in western US - Vx and captive breeding may be needed to protect endangered species - Emergency planning and vaccination is already happening fro the endangered Columbian basin pygmy rabbit in Washington and riparian brush rabbit in California - Monitoring of wild lagomorphs and their predators as well as research evaluating interactions of RHD with other stressors (habitat loss, etc) need to be understood

Answer 71

Species Susceptibility and Transmission Dynamics * RHDV= European rabbit * EBHSV= European Hares * RHDV2= infection of many leporids * Unknown if pikas are susceptible * Transmission= oral, nasal or conjunctival routes or skin trauma, urine, feces, and respiratory secretions * Rabbits may shed the virus for 30 days after recovery (RHDV) * Virus survives heat/freezing * Readily spreads on fomites * Predators and scavengers may be mechanical vectors: with nucleic acids of RHDV and EBHSV found in feces of various carnivores * Impacts of RHDV is greater in arid regions compared to cooler, humid areas

Answer 72

Clinical Disease Manifestation and Diagnosis of RHDV * Incubation period and time to death for RHDV and EBHSV is short * RHDV2 has a slightly longer incubation period * Young animals seem resistant to RHDV and EBHSV * Peracute disease= sudden death without clinical signs * Acute disease= anorexia, apathy, conjunctival congestion, neurologic signs, respiratory signs, foamy or bloody discharge, lacrimation, ocular hemorrhage and epistaxis * Subacute disease=signs are milder, and survivors develop antibodies * Chronic= anorexia, lethargy and jaundice precede death by 1-3 weeks * DDx: tularemia, septicemic pasteurellosis, atypical myxomatosis, enterotoxemia, plague, anticoagulant rodenticides, heat exhaustion, trauma or other cause of severe septicemia with secondary DIC * Treatment= supportive care * Primary tissues= liver, lung, spleen -- Virus replication in liver within first hours of infection= necrotic and apoptotic cell death of hepatocytes -- Acute necrotizing hepatitis and DIC with multiple organ failure -- Animals= good body condition and have blood in nares or reddened conjunctiva * Gross lesions= hepato/splenomegaly, hepatic pallor or congestion (may have mild reticular pattern), hyperemia, pulmonary congestion, and hemorrhages in multiple organs * Histo= acute hepatic necrosis, pulmonary congestion, hemorrhages and fibrin microthrombi in capillaries * Diagnostic test of choice= RT-PCR (liver being preferred sample) * Serologic detection of antibodies can be doe with ELISA or HI * Iso-ELISA= provide titers for IgA, IgM, and IgG * **Reportable**

Answer 73

Control and Prevention * Effective ingredients = potassium peroxymonosulfate, sodium hypochlorite (bleach diluted with water 1:10), accelerated hydrogen peroxide (Rescue), Alkaline phenolic germicidal detergent * Disease eradication is not feasible so efforts should be made toward reduced anthropogenic spread and controlling disease in domestic rabbits * Strict biosecurity: sanitation, disinfection and quarantine * Field necropsies SHOULD NOT BE PERFORMED (ddx tularemia and plaque)- whole carcasses double bagged and transported to Biologic Safety Level2 or higher containment lab * Vaccination has been employed for domestic rabbits, captive wild rabbits, and endangered species (vx to specific strain or combined is needed due to no crossover protection between RHDV/RHDV2) * Precautions for outdoor recreationists, falconers, and hunters Impacts to Wildlife and Ecosystems * European rabbit= valuable game animal and keystone prey species is severely affected (also by habitat loss and myxomatosis) * Endangered Iberian lynx and Spanish Imperial Eagles depend on this rabbit for prey * In North America- unknown- bobcats and golden eagles need to be monitored as their population could be affected as rabbits die off * Cottontails and jackrabbits have already declined in numbers in western US * Vx and captive breeding may be needed to protect endangered species * Emergency planning and vaccination is already happening fro the endangered Columbian basin pygmy rabbit in Washington and riparian brush rabbit in California * Monitoring of wild lagomorphs and their predators as well as research evaluating interactions of RHD with other stressors (habitat loss, etc) need to be understood