Thea experiments

Question 1

What was observed in the Pike’s Peak expedition regarding haematocrit levels?

Answer 1

Graded haematocrit increase above 55% with altitude.

Question 2

What did blood samples from 132 miners indicate about haematocrit levels?

Answer 2

Higher haematocrit at higher altitude.

Question 3

What was the overall conclusion regarding haematocrit levels and altitude?

Answer 3

Difficulty to extrapolate and all just causation.

Question 4

What was found about erythrocytosis in Tibetans at high altitude?

Answer 4

Same distribution of Hb for Tibetans at 4000m altitude and US individuals at sea level.

Question 5

How do Aymara individuals’ Hb levels compare to Tibetans at 4000m?

Answer 5

Aymara have higher Hb levels than Tibetans at 4000m.

Question 6

What genetic association was found in Tibetan highlanders?

Answer 6

Natural selection on EPAS1 (HIF2A) associated with low haemoglobin concentration.

Question 7

What was the significance of the SNPs found in Tibetans?

Answer 7

8 SNPs genome-wide significance (p < 2.81x 10-7), associated with EPAS1.

Question 8

What was the association of EPAS1 genotype with haemoglobin levels in Tibetans?

Answer 8

Homozygotes (major allele) have a Hb ~1 g/dL lower than heterozygotes.

Question 9

What was the finding regarding EPAS1 expression in CMS patients?

Answer 9

Higher EPAS1 expression in bone marrow erythroblasts of CMS patients.

Question 10

What correlation was found with EPAS1 expression in CMS patients?

Answer 10

Positively correlated with erythrocyte number and negatively correlated with SaO2.

Question 11

What was the limitation of the study on EPAS1 expression?

Answer 11

K562 cells derived from a cancerous line may be unrepresentative of normal lymphoblasts.

Question 12

What was the conclusion regarding pulmonary artery pressure and vascular resistance at altitude?

Answer 12

Sustained increase in PAP and PVR with altitude.

Question 13

What were the results of the hypobaric chamber study on male athletes?

Answer 13

Increase in pulmonary artery pressure and vascular resistance with altitude.

Question 14

What was the conclusion regarding prolonged hypoxia and its effects?

Answer 14

Increased PAP and PVR can lead to RV hypertrophy, cor pulmonale, and precipitate HAPE.

Question 15

What was the finding regarding HPV in Tibetans?

Answer 15

Absence of HPV in Tibetans at 3600m.

Question 16

What was the effect of iron availability on pulmonary hypertension?

Answer 16

Iron supplementation can alleviate hypoxic pulmonary hypertension.

Question 17

What was the conclusion regarding acclimatisation and acid-base status?

Answer 17

Evidence against acclimatisation triggered by acid-base status.

Question 18

What was the significance of HIF mediation in ventilatory acclimatisation?

Answer 18

Inactivation of HIF-2alpha impaired ventilatory acclimatisation to chronic hypoxia.

Question 19

What is the role of HIF in ventilatory acclimatisation?

Answer 19

HIF mediation is essential in modulating ventilatory sensitivity to hypoxia through acting at the carotid bodies.

Question 20

What happens when PHD2 is inactivated?

Answer 20

Inactivation of PHD2 using tamoxifen results in enhanced hypoxic ventilatory responses, which can be compensated for by inactivating HIF-2alpha, but not HIF-1alpha.

Question 21

How does HIF-2alpha inactivation affect acclimatisation to chronic hypoxia?

Answer 21

Inactivation of HIF-2alpha impairs ventilatory acclimatisation to chronic hypoxia and carotid body proliferation.

Question 22

What is AMS and its cause?

Answer 22

AMS is due to hypoxia, not hypobaria.

Question 23

What did Paul Bert’s 1978 study reveal about AMS?

Answer 23

A pressure chamber and a bird lost consciousness at the same PO2 regardless of pressure, indicating AMS is related to hypoxia.

Question 24

What limitation was noted in AMS studies?

Answer 24

There was no control of PCO2, and loss of consciousness is not directly a symptom of AMS.

Question 25

What did Karinen's 2010 study link to AMS susceptibility?

Answer 25

The study linked hypoxemia with AMS susceptibility and measured resting and exercise Spo at various altitudes.

Question 26

What was the outcome of the resting oxygen saturation study at 2600m?

Answer 26

30% of participants met Lake Louise criteria for AMS later on, but the difference in oxygen saturation was less than 1%, which was not clinically significant.

Question 27

What distinguishes HACE from AMS?

Answer 27

Microbleeds are a feature of HACE but not AMS.

Question 28

What did Kellenberg's 2008 study find regarding HACE?

Answer 28

MRI imaging showed evidence of hemosiderin deposits in patients recovering from HACE but not in AMS controls.

Question 29

What was the key finding of Severinghaus's 1966 study?

Answer 29

There was a 24% increase in cerebral blood flow 6-8 hours after rapid ascent to 3810m.

Question 30

What did Hacket's 1998 study reveal about HACE?

Answer 30

Vasogenic oedema is most prominent along white matter tracts in the brain in HACE patients.

Question 31

What did Wang's 2018 study indicate about cytotoxic oedema in HACE?

Answer 31

Upregulation of the AQP4 channel may contribute to early cytotoxic oedema in HACE.

Question 32

What did Gruenig's 2000 study suggest about HAPE susceptibility?

Answer 32

Exercise testing could predict HAPE susceptibility based on pulmonary arterial systemic pressure responses.

Question 33

What did Maggiorni's 2001 study conclude about HAPE?

Answer 33

Early HAPE is caused by an increase in pulmonary capillary pressure, not an increase in permeability.

Question 34

What is the conclusion of Swenson's 2002 study regarding HAPE?

Answer 34

Inflammation is a tertiary consequence of hydrostatic oedema in HAPE, not a causative factor.

Question 35

What did Groves's 1987 study find about pulmonary hypertension?

Answer 35

Pulmonary vascular resistance rises with altitude, steepening the relationship between cardiac output and pulmonary pressure.

Question 36

What characterizes HAPE?

Answer 36

HAPE is characterized by an increase in pulmonary arterial pressure that causes damage to the alveolar wall, leading to fluid leakage without initial inflammation. Observed inflammation is a tertiary consequence of hydrostatic edema and altered permeability.

Question 37

What happens to pulmonary vascular resistance with altitude?

Answer 37

Pulmonary vascular resistance rises with altitude, and the relationship between cardiac output and pulmonary pressure steepens, indicating a progressively less distensible pulmonary circulation.

Question 38

What was observed in the study of supraventricular arrhythmias in cold shock response?

Answer 38

In a study of breath-hold submersions in cold water, ectopic arrhythmias occurred in 11 of the 12 subjects tested. The incidence of these arrhythmias was noted around the time the diving response was initiated, leading to pronounced bradycardia.

Question 39

What limitation was noted in the study of supraventricular arrhythmias?

Answer 39

The study had a limitation of no in vivo animal studies.

Question 40

What was the significant finding in the study of pulmonary arterial pressure in IPO-predisposed individuals?

Answer 40

The first direct measurement of pulmonary arterial pressure showed significantly increased pressure in IPE-susceptible patients during moderate exercise in water, which was abolished when pre-treated with sildenafil.

Question 41

What does the model for nitrogen narcosis suggest?

Answer 41

Computer simulations indicated that nitrogen solubilized within an aqueous solution takes only 100ns to partition in the lipid bilayer, which could explain nitrogen narcosis.

Question 42

What limitation was noted in the nitrogen narcosis model study?

Answer 42

The limitation was that only one type of phospholipid (DPPC) was used in the lipid bilayer, which is not representative of human synapses.

Question 43

What did the study on acute oxygen toxicity effect on lungs find?

Answer 43

The study found that combat swimmers exposed to hyperbaric challenges had increased DNA breaks and superoxide radical generation compared to non-diving endurance-trained controls.

Question 44

What limitation was noted in the acute oxygen toxicity effect on lungs study?

Answer 44

The limitation was unclear regarding how many genetic aberrations were maintained, as breaks resolved within an hour, requiring single-cell sequencing for variability quantification.

Question 45

What were the findings regarding acute oxygen toxicity effect on CNS?

Answer 45

Rats exposed to 5atm 100% O2 until seizures showed increased nitrotyrosine and carbonyl content, implicating NO as an intermediary in oxidative stress.

Question 46

What limitation was noted in the acute oxygen toxicity effect on CNS study?

Answer 46

The limitation was that the used nNOS inhibitor seemed unselective, potentially affecting eNOS and preventing vasodilation.

Question 47

What did the barotrauma study on dogs reveal?

Answer 47

The study indicated that transpulmonary pressures of more than 60-70 mmHg could cause alveolar ruptures, with necropsy showing arterial gas emboli and emphysema.

Question 48

What limitation was noted in the barotrauma study?

Answer 48

The limitation was ethical concerns.

Question 49

What were the findings on venous gas embolism and the endothelium?

Answer 49

The study found that more rapid ascent during simulated air dives correlated with increased bubble formation and endothelial damage, suggesting decompression bubbles are significant in assessing decompression stress.

Question 50

What limitation was noted in the venous gas embolism study?

Answer 50

The limitation was that the findings were correlational; ex vivo studies could introduce bubbles with wire myography.

Question 51

What did the study on exercise and diving find?

Answer 51

The study found that a single sub-maximal period of exercise before immersion reduced bubble grades in divers.

Question 52

What limitation was noted in the exercise and diving study?

Answer 52

The limitation was that 45 minutes of exercise might not be feasible before many recreational dives, particularly at sea.

Question 53

What did the Lorraine Smith effect of O2 study conclude?

Answer 53

The study concluded that exposure to different partial pressures of hyperbaric oxygen caused inflammation and lung damage, with significant endothelial cell damage observed.

Question 54

What limitation was noted in the Lorraine Smith effect of O2 study?

Answer 54

The limitation was that even shorter exposure times were longer than most dives.