Lecture 8: Cardiac Ischemia

Question 1

What is ischemia?

Answer 1

Coronary flow is inadequate to maintain steady state metabolism, oxygen demand exceeds oxygen supply.

Question 2

What are the symptoms of ischemia?

Answer 2

Often no symptoms, may have angina pectoris (chest strangling)

Question 3

What causes angina pectoris?

Answer 3

Adenosine and lactate activation of pain nerve endings

Question 4

What things increase oxygen demand?

Answer 4

Ventricular wall stress, heart rate and contractility

Question 5

What increases ventricular wall stress?

Answer 5

Increase wall thickness, increase intraventricular pressure, increase systolic pressure, increased stretch

Question 6

What increases heart rate?

Answer 6

Cardiac cycle expenditure (increase ATP splitting, calcium homeostasis, cross bridge activity)

Question 7

What increases contractility?

Answer 7

Inotropic state, energy expenditure, sympathetic activity

Question 8

What increases oxygen supply?

Answer 8

Diastolic pressure, coronary resistance, oxygen carrying capacity

Question 9

What increases diastolic pressure?

Answer 9

Coronary flow at max, aortic diastolic pressure

Question 10

What increases coronary resistance?

Answer 10

Max at systole, vessel compression, vascular tone via autoregulation, vessel obstruction

Question 11

What increases oxygen carrying capacity?

Answer 11

Hb levels, oxygen saturation (usually at maximum so don’t have much leeway)

Question 12

What are the metabolic constrictors and dilators?

Answer 12

Oxygen

Adenosine,lactate,H,CO2

Question 13

What are the endothelial constrictors and dilators?

Answer 13

ET-1

NO

Question 14

What are the neural/hormonal constrictors and dilators?

Answer 14

Alpha-1

Beta-1

Question 15

What is coronary dysfunction?

Answer 15

Endothelial cell dysfunction, reduced NO, too much unopposed vasoconstriction

Question 16

What causes auto regulatory failure/thrombosis?

Answer 16

Local regulatory responses impaired, oxygen demand not matched by supply, loss of NO mediated suppression of platelet aggregation

Question 17

What are the stages of atherosclerosis?

Answer 17

Normal arterial wall
Fatty streak/initial phase
Stable Plaque
Vulnerable plaque

Question 18

What are the features of a normal arterial wall?

Answer 18

Elastic, endothelial cells release NO, smooth muscle cells controlling how open vessel is

Question 19

What happens to develop fatty streak?

Answer 19

Macrophages ingest lipids and form fatty streaks and smooth muscle cells migrate to elastic region

Question 20

What is stable plaque?

Answer 20

Lipid core expands, smooth muscle cells proliferate, plaque bulges with fibrous cap

Question 21

What is vulnerable plaque?

Answer 21

Fibrous cap ruptures, collages exposed, platelets stick and trigger clot formation, clot occludes downstream flow

Question 22

What are 90% of MIs due to?

Answer 22

Plaque rupture - thrombus formation

Question 23

What is the pain like in MI?

Answer 23

Similar to angina and pain is present at rest

Question 24

What percentage of MI patients do not experience pain?

Answer 24

25%

Question 25

How do you measure whether an MI is occurring?

Answer 25

Measure markers that are released from cardiomyocytes when they split - CK, TnT, TnI

Question 26

When do the cardiomyocyte markers present and when do they peak?

Answer 26

4-8 hours | 24 hours

Question 27

What is an infarct?

Answer 27

Irreversible necrosis of myocardium due to prolonged intense ischemia

Question 28

What is stunning?

Answer 28

Prolonged contractile depression, delayed recovery

Question 29

What is hibernation?

Answer 29

Chronic metabolic suppression, recovery with re-flow

Question 30

What is the brief post MI timeline?

Answer 30

``` 10 mins: cell swells 20-24 mins: irreversible cell injury (starts inflammatory processes) 18-24 hours: necrotic process 1 week: thinning of muscle 7 weeks: fibrosis and scarring complete ```

Question 31

What is the effect of ischemia on the cardiac ECC?

Answer 31

Oxygen and ATP are low. Pumps are disabled. Hydrogen ions build up due to anaerobic processes and are pumped out of the cell, moving sodium in. The sodium concentration in the cell becomes high so the Ca/Na exchanger operates in reverse mode and moves Na out and Ca in - Ca build up in the cell - Ca overload!

Question 32

What happens when you alter the cardiac muscle RMP?

Answer 32

Arrhythmia

Question 33

What is reperfusion?

Answer 33

Reinstating the blood flow to the heart to restore oxygen availability to combat ischemia

Question 34

What is the risk of reperfusion?

Answer 34

Oxygen paradox - further increase heart dysfunction and death

Question 35

What happens when the blood flow is reinstated to the heart?

Answer 35

Hydrogen ions outside the cell are flushed away, and the proton gradient is restored. Hydrogen ions move out of the cell and sodium moves in. Increased sodium in the cell so it moves out and Ca moves in - calcium overload.

Question 36

What does calcium overload cause?

Answer 36

Contractual dysfunction, fatal arrhythmias, cardiomyocyte death

Question 37

What activates CAMK II and what does it do?

Answer 37

Activated by increases in calcium and upregulates transporters

Question 38

What happens when CAMK II is active in ischemic cell?

Answer 38

Increases pump activity - calcium overload - cell pumps really hard - death

Question 39

What inhibits CAMK II and what does it reduce?

Answer 39

KN93 - reduced prevelance of arrhythmia and cardiomyocyte death

Question 40

What are the levels of plaque obstruction/stenosis?

Answer 40

90% - Basal ischemia, out of breath at rest. 100 % - Thrombosis – total occlusion 70% - minimal impact on flow, compensatory dilatation 70-90 % - episodic ischemia - pain during physical activity