Reperfusion Injury Flashcards Preview

CRP- Cardiology > Reperfusion Injury > Flashcards

Flashcards in Reperfusion Injury Deck (17):
1

What happens to the cardiomyocyte during ischemia?

switches to anaerobic respiration (glycolysis) generating lactic acid, lowering the pH, and inhibiting myofibril contracture.

2

What happens to the cardiomyocyte during reperfusion?

washout of lactic acid occurs and restoration of physiological pH, however this leads to uncoupling of the electron transport chain in the mitochondria, generating ROS, opening the MPTP and stimulating the SR to release excess calcium causing myofibril hypercontracture= BAD causing elevated LVEDP.

3

Why is timely reperfusion necessary?

to reduce the accumulating infarct size that occurs as a result of ischemia

4

What are some characteristics of I/R injury?

1. increased ROS= due to incomplete reduction of O2, uncoupled eNOS (oxidation of BH4 to BH2), or SO generation.
2. Initiate lipid peroxidation= cytokine release
3. leukocyte chemotaxis= TNFa from injured cells attracts leukocytes
4. decreased endothelial derived NO= SO combines with NO forms peroxynitrite :(

5

Is INHIBITING eNOS UNCOUPLING a good thing or bad thing?

GOOD thing

6

What is the time course of events in myocardial I/R?

2-5 min= endothelial dysfunction (low NO, more ROS)
10 min= upregulation of P-selectin (mediated by PCAM-1)
20 min= increased adhesion of PMNs to endothelium
30 min= PMN migration into myocardium
* AKA stop the ROS or increase the NO, ASAP

7

What are the biochemical mechanism of ROS in I/R?

I/R sitimulates cytokine receptors, which stimulates DAG, activating PKC, which uncouples eNOS causing the oxidation of BH4 to BH2 :(

8

What are the types of experimental I/R injury?

1. clinical I/R injury (ischemic heart disease)
2. Experimental I/R injury= acute ischemia vs. preconditioning

9

What causes ischemic heart disease (IHD)?

coronary artery disease (atherosclerotic coronary arterial disease)

10

How can we restore blood flow?

1. angioplasty (PCI)
2. thrombolysis
3. Coronary artery bypass and grafting

11

What treatments attenuate I/R injury?

currently there are no therapeutics to treat this.
Experimentals:
- anti-oxidants (vitamin E) but not benefical
- NO bioavailability enhancer (inhibit uncoupled eNOS)
- Anti-inflammation

12

***What is PREconditioning?

-PRIMING THE HEART by inducing BRIEF periods of ISCHEMIA (3 min I/R x 3) protects the organ from prolonged ischemic damage and reperfusion injury prior to reperfusion. Basically think pumping up a blood pressure cuff and releasing it 3 times to protect/prime the heart from later prolonged ischemia.
-biochemical response is mediated by PKC EPSILON ACTIVATION involving activation of mitochondrial K-ATP channels. Remember, PRIOR to prolonged ischemia!

13

****What is POSTconditioning?

PKC EPSILON INHIBITION during REPERFUSION is associated with restoration of post-reperfused organ function; attenuates H2O2 release and enhances endothelial-derived NO bioavailability :)

14

What is the role of eNOS in I/R injury?

eNOS normally produces NO from L-arginine with the co-factor BH4 (tetrahydrobiopterin).
However in I/R, BH4 becomes oxidized to BH2 causing eNOS uncoupling, and thus SO production instead of NO.

15

What will BH4 do to cardiac function in I/R injury?

attenuates I/R injury :)

16

What will BH2 do to cardiac function in I/R injury?

augment I/R injury due to more uncoupled eNOS :(

17

What does SOD do and is it good or bad?

converts SO to O2 or H2O2 (GOOD THING).