Ischemia/Reperfusion- Exam 2 Flashcards Preview

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Flashcards in Ischemia/Reperfusion- Exam 2 Deck (46):
1

Ischemia

Blood supply problem

2

Injury

cellular damage

3

Infarction (necrosis)

cell death

4

What will the EKG show with myocardial ischemia?

Depressed ST segment
Inverted T wave

5

What causes myocardial ischemia?

Not enough blood
atherosclerosis
vasospasm
thrombosis
embolism

6

What will the EKG show for myocardial infarction?

Pathologic Q waves; permanently

7

What is released with myocardial infarction?

Troponin

8

What will the EKG show for myocardial injury?

Elevated ST segment

9

Oxygen Free Radicals

Reactive Oxygen Species (ROS)
Altered O2 molecules created; at XC and reperfusion; reactions add unpaired electrons to outer orbit

10

5 reactions leading to O2 Radical Formation

1. NADPH + O2 = Superoxide O2-
2. Superoxide Dismutase O2- -> Hydrogen Peroxide H2 O2
3. Hydrogen peroxide + myeloperoxidase= hypochlorite HOCL

4. Hydrogen peroxide + Catalase = O2 + H20
5. Hydrogen peroxide + Fe++ = Hydroxyl Radical OH

11

How are reactive oxygen species created?

Xanthine oxidase releases in endothelial cells; catalyze: hypoxanthine to xanthine to uric acid

12

What enzyme is important in purine breakdown path?

Xanthine oxidase

13

Total depletion of O2; complete lack of O2

Anoxia

14

Lack of oxygen delivered to tissues

Hypoxia

15

Lack of blood supply

ischemia

16

Restoration of circulation

Reperfusion; can result in inflammation and oxidative damage through inducing oxidative stress rather than restoration of normal funcion

17

What abrupt biochemical and metabolic changes occur resulting in reperfusion injury?

Mitochondrial reenergization
Generative of reactive oxygen species
Intracellular calcium overload
Rapid restoration of physiologic pH
Inflammation

18

What does cell death result from? (related to reperfusion injury)

Opening of mitochondrial permeability transition pore and induction of cardiac myocyte hyper-contraction

19

What protects the heart from free radicals?

Antioxidant system (electron donators)

20

What are the three antioxidant system components?

Superoxide dismutase
Catalase
Glutathione reductase

21

What is the 5' nucleotidase system?

Converts AMP to adenosine

22

When is full recovery impossible?

If adenosine nucleotide pool <50% full recovery

23

What are the mediators of lethal reperfusion injury?

Oxygen paradox
Calcium paradox
pH paradox
Inflammation
Myocardial edema

24

oxygen paradox

too much of a good thing: oxygen-derived free radical formation (reactive oxygen species ROS)

25

calcium paradox

large influx of calcium into the cell

26

pH paradox

pH moves from acidic to normal- potentiates many of hte changes

27

inflammation

neutrophil activation

28

What is depleted during ischemia?

Tissue stores of endogenous antioxidants
-Superoxide dismutase
-catalase
-glutathione
-glutathione peroxidase

29

What factors determine the amount of oxygen free radicals produced?

Severity of ischemic injury
actiavtion and recruitment of neutrophils to myocardium
Level of O2 in the cardioplegic solution
presence of endogenous scavengers and inhibitors

30

What changes are caused my oxygen free radicals?

Peroxidation of lipid components of myocellular membranes (steal electrons from lipid membranes)

Impairment of vascular endothelial function; produces vasoactive and autoinflammatory autocoids

31

Autocoids

act like local hormones, act near sites of synthesis, short acting

32

What are the results of oxygen free radicals? (Know this)

Postischemic dysfunction
Dysrhythmias
morphologic injury
necrosis

33

How do Oxygen free radicals cause injury?

Induce opening of mitochondrial permeability transition pore
act as neutrophil chemoattractants
mediate dysfunction of SR
contribute to intracellular calcium overload
damage cell membrane by lipid peroxidation
induce enzyme denaturation
cause direct oxidative damage to DNA

34

What is the mitochondrial permeability transition pore?

Nonselective channel (protein)of inner mitochondrial membrane
when open increases the permeability of molecules <1500 daltons
when open oxidative phosphorylation is uncoupled (results in decrease in atp and cell death)

35

When is the mitochondrial permeability transition pore closed?

During ischemia

36

When is the mitochondrial permeability transition pore open?

During reperfusion; opens in response to mitochondrial calcium overload oxidative stress, resotration of physiologic pH, and ATP depletion

37

How can we combat the oxygen free radical problem?

Drugs that inhibit their formation (anesthetic agents, antiarrythmics may eliminate hydroxyl radicals, vitamin C peroxides)

Drugs that scavenge/remove them
Antineutrophil agents (decrease ischemia reperfusion injury)

38

What drugs remove oxygen free radicals?

Mannitol, N-acetylcysteine

39

What changes are cause by myocyte calcium influx?

Depletion of high-energy phosphate stores;
Accumulation of mitochondria kills ability to produce ATP
Activation of catalytic enzymes
Alteration of excitation-contraction coupling of actin-myosin-tropnin

40

Inability to produce ATP affects what?

Ability of the cell to contract
Ability of the cell to move calcium out of hte cell or back into the SR

41

What does activation of catalytic enzymes do?

increase cellular damage

42

Stone heart syndrome

calcium not removed after going onto the cell causing contraction sequence; can enter by multiple pathways

43

What are the three types of receptor molecules that activate neutrophils?

selectins (P, L, E)- inital binding
Beta2 integrins (CD11/CD18 complex)- firmer contact
Immunoglobulin superfamily (ICAM-1)- final surface adherance

44

Diapedesis

once bound to receptor molecule, blood goes through capillaries

45

What starts the activation of neutrophils?

P-selectin (endothelial cells) triggered by proinflammatory mediators (oxygen-derived free radicals/hydrogen peroxide) thrombin, complement components, histamine

46

What causes myocardial edema?

Increased intracellular osmotic pressure
disruption of electrical potential across membrane
increased microvascular permeability
increased intersitial osmotic pressure
high cpg delivery pressure
hypothermia induced changes to sodium potassium pump