Myocardial oxygen supply, demand, and ischemia Flashcards
determinants of myocardial oxygen supply
- heart rate
- contractility
- ventricular wall stress (blood pressure, ventricular chamber radius, ventricular wall thickness)
relationship between blood pressure and wall stress
increase in blood pressure- increase in wall stress
relationship between radius of ventricle wall and wall stress
increase in radius of ventricle- increase in wall stress
relationship between ventricular wall thickness and wall stress
increased ventricular wall thickness- less wall stress (less stress on each individual myocyte)
determinants of myocardial oxygen supply
oxygen content (hemoglobin level, oxygen saturation); oxygen extraction; coronary blood flow
list the components of coronary blood flow
coronary perfusion pressure coronary resistance (myocardial R, arteriolar R, epicardial R)
list factors that contribute to arteriolar resistance
vascular tone, local metabolites, endothelial function
list factors that affect epicardial resistance
atherosclerosis
write an equation for calculating coronary blood flow
CBF = (Postium-PCS)/(Rart + Rmyo + REpi)
highest flow through the left coronary artery is during early ______
diastole (aortic valve open, muscles not contracting)
myocardial resistance is greater in the ____ than in the _________
subendocardium; epicardium
arteriolar resistance is adjusted in response to metabolic factors, including…
adenosine, prostaglandins, NO, endothelin, potassium, oxygen
explain autoregulation in the context of arteriolar resistance
resistance, R- art, is dynamic and varies in response to local conditions to titrate the blood flow into the local tissue
describe coronary flow reserve
Ability to increase blood flow is related to the ability to reduce R-art. When the arterioles are not maximally dilated (R-art is not maximally reduced) there remains some coronary flow reserve
If an artery is temporarily occluded, metabolic substances build up and dilate the arterioles/ decrease arteriolar resistance.
R-myo is due to compression of the perforating arteries within ventricular muscle in ________.
systole
R-epi can become important in the case of ________
atherosclerosis
the only way to meaningfully increase oxygen supply to the heart is to increase__________
coronary blood flow
what is the primary mechanism of regulating coronary blood flow
alter resistance to flow in coronary arteries (R-art)
describe reactive hyperemia and how it relates to coronary flow reserve
If an artery is temporarily occluded, metabolic substances build up and dilate the arterioles/ decrease arteriolar resistance. When occlusion is removed, CBF increases above baseline due to low resistance that that was developed during occlusion. The amount of flow increase above baseline is called reactive hyperemia and represents the amount of available coronary flow reserve.
what compound is considered the primary link between myocardial oxygen consumption and coronary blood flow
adenosine
describe the impact of epicardial stenosis on coronary flow reserve
As R-epi increases, R-art must decline in order to maintain constant flow rates in the myocardium and keep total coronary resistance the same. This “uses up” coronary flow reserve
most arteriolar reserve is lost at around ____% stenosis, and coronary blood flow becomes strictly dependent on ____________
90%; perfusion pressure
* there will be ischemia at rest
list mechanisms of increased myocardial oxygen demand
increased heart rate, increased contractility, increased ventricular wall stress
list mechanisms of decreased myocardial oxygen supply
ex in anemia, low coronary perfusion pressure, increased perssure in coronary sinus, reduced arterial oxygen saturation, atherosclerotic plaque rupture with thrombus, endothelial dysfunction
CAD leads to limited coronary blood flow by:
fixed narrowing, endothelial dysfunction, increased R-epi
list initial cellular effects of ischemia
- reduced ATP, initially ADP and creatinine phosphate preserve ATP
- anaerobic metabolism, increases lactic acid production and decreases pH
- elevated H+ in the cell opens the K-ATPase channels
list effects of opening the K-ATPase channel
loss of potassium gradient, contractile dysfunction. likely self-protective mechanism allowing cell to survive transient periods of ischemia
later cellular effects of ischemia
- ATP depletion–> loss of Na/K ATPase pump function
- cell membrane loses integrity, Na and water flow in
- proteases leak out, degrade myofibrils
- ## inflammatory infiltration of neutrophils
list electrical and mechanical effects of ischemia
electrical: dysfunction of SA/AV nodes, arrhythmias
mechanical: impaired muscle relaxation, increases filling pressure, decreases compliance, impaired contraction
list four types of myocardial reperfusion injury
myocardial stunning
no reflow
reperfusion arrhythmia
fatal reperfusion injury
define myocardial stunning
ventricular dysfunction that persists after reperfusion despite absence of irreversible damage and despite restoration of normal blood flow. Likely because cell is intact but torponin mechanism is damaged due to Ca changes, so the cell won’t beat for a while. After 7-14 days protein synthesis= new troponin, cell can recover function
what is the likely cause of no reflow after opening an occluded epicardial artery
edema, destruction of small vascular structures in myocardium
what is the role of O2 in reperfusion injury
oxygen radicals injure cells, reduce NO
what is the role of calcium in reperfusion injury
Abrupt rise in intracellular Ca++ is caused by damage to sarcolemmal membrane and SR
High Ca++ leads to myocyte hypercontracture, increasing O2 demand
describe the phenomenon of ischemic pre-conditioning
people with previous “stuttering angina” have smaller MIs
likely involves the K-ATP channel
list clinical effects of ischemia
- chest pain
- decreased ventricular relaxation- decrease in diastolic compliance of ventricle, elevation of diastolic ventricular pressure, because ventricle is stiffer.
- S4 sound may be heard as a result of reduced ventricular compliance
- decreased myocardial contractility: anaerobic metabolites depress myofibrilar function- protons decease affinity of calcium binding to troponin C, thus decrease sensitivity of myofibrils to calcium
differentiate between myocardial stunning and hibernating myocardium
- Stunning: transient total occlusion- ventricular dysfunction that persists after reperfusion despite absence of irreversible damage and despite restoration of normal blood flow
- Hibernation: constant partial flow -result of chronic partial occlusion, reduced function but myocytes are alive and will recover function if blood flow improves
what diagnostic study is best to clarify chest pain
history
what diagnostic study is best to clarify cellular electrical changes
ECG, stress ECG
what diagnostic study is best to clarify reduction in coronary blood flow
myocardial perfusion stress test, coronary angiography, stress echocardiogram, stress MRI
what diagnostic study is best to clarify conversion to anaerobic metabolism
PET scan
what diagnostic study is best to clarify systolic dysfunction/ impaired contractility
echocardiogram, MRI, CT, physical exam
what diagnostic study is best to clarify diastolic dysfunction/ impaired relaxation
echocardiogram, MRI, physical exam
