Lecture 8: Cardiac Ischemia Flashcards
What is ischemia?
Coronary flow is inadequate to maintain steady state metabolism, oxygen demand exceeds oxygen supply.
What are the symptoms of ischemia?
Often no symptoms, may have angina pectoris (chest strangling)
What causes angina pectoris?
Adenosine and lactate activation of pain nerve endings
What things increase oxygen demand?
Ventricular wall stress, heart rate and contractility
What increases ventricular wall stress?
Increase wall thickness, increase intraventricular pressure, increase systolic pressure, increased stretch
What increases heart rate?
Cardiac cycle expenditure (increase ATP splitting, calcium homeostasis, cross bridge activity)
What increases contractility?
Inotropic state, energy expenditure, sympathetic activity
What increases oxygen supply?
Diastolic pressure, coronary resistance, oxygen carrying capacity
What increases diastolic pressure?
Coronary flow at max, aortic diastolic pressure
What increases coronary resistance?
Max at systole, vessel compression, vascular tone via autoregulation, vessel obstruction
What increases oxygen carrying capacity?
Hb levels, oxygen saturation (usually at maximum so don’t have much leeway)
What are the metabolic constrictors and dilators?
Oxygen
Adenosine,lactate,H,CO2
What are the endothelial constrictors and dilators?
ET-1
NO
What are the neural/hormonal constrictors and dilators?
Alpha-1
Beta-1
What is coronary dysfunction?
Endothelial cell dysfunction, reduced NO, too much unopposed vasoconstriction
What causes auto regulatory failure/thrombosis?
Local regulatory responses impaired, oxygen demand not matched by supply, loss of NO mediated suppression of platelet aggregation
What are the stages of atherosclerosis?
Normal arterial wall
Fatty streak/initial phase
Stable Plaque
Vulnerable plaque
What are the features of a normal arterial wall?
Elastic, endothelial cells release NO, smooth muscle cells controlling how open vessel is
What happens to develop fatty streak?
Macrophages ingest lipids and form fatty streaks and smooth muscle cells migrate to elastic region
What is stable plaque?
Lipid core expands, smooth muscle cells proliferate, plaque bulges with fibrous cap
What is vulnerable plaque?
Fibrous cap ruptures, collages exposed, platelets stick and trigger clot formation, clot occludes downstream flow
What are 90% of MIs due to?
Plaque rupture - thrombus formation
What is the pain like in MI?
Similar to angina and pain is present at rest
What percentage of MI patients do not experience pain?
25%
How do you measure whether an MI is occurring?
Measure markers that are released from cardiomyocytes when they split - CK, TnT, TnI
When do the cardiomyocyte markers present and when do they peak?
4-8 hours
24 hours
What is an infarct?
Irreversible necrosis of myocardium due to prolonged intense ischemia
What is stunning?
Prolonged contractile depression, delayed recovery
What is hibernation?
Chronic metabolic suppression, recovery with re-flow
What is the brief post MI timeline?
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
What is the effect of ischemia on the cardiac ECC?
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!
What happens when you alter the cardiac muscle RMP?
Arrhythmia
What is reperfusion?
Reinstating the blood flow to the heart to restore oxygen availability to combat ischemia
What is the risk of reperfusion?
Oxygen paradox - further increase heart dysfunction and death
What happens when the blood flow is reinstated to the heart?
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.
What does calcium overload cause?
Contractual dysfunction, fatal arrhythmias, cardiomyocyte death
What activates CAMK II and what does it do?
Activated by increases in calcium and upregulates transporters
What happens when CAMK II is active in ischemic cell?
Increases pump activity - calcium overload - cell pumps really hard - death
What inhibits CAMK II and what does it reduce?
KN93 - reduced prevelance of arrhythmia and cardiomyocyte death
What are the levels of plaque obstruction/stenosis?
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
