Myocardial oxygen supply, demand, and ischemia

Question 1

determinants of myocardial oxygen supply

Answer 1

• heart rate
• contractility
• ventricular wall stress (blood pressure, ventricular chamber radius, ventricular wall thickness)

Question 2

relationship between blood pressure and wall stress

Answer 2

increase in blood pressure- increase in wall stress

Question 3

relationship between radius of ventricle wall and wall stress

Answer 3

increase in radius of ventricle- increase in wall stress

Question 4

relationship between ventricular wall thickness and wall stress

Answer 4

increased ventricular wall thickness- less wall stress (less stress on each individual myocyte)

Question 5

determinants of myocardial oxygen supply

Answer 5

oxygen content (hemoglobin level, oxygen saturation); oxygen extraction; coronary blood flow

Question 6

list the components of coronary blood flow

Answer 6

coronary perfusion pressure
coronary resistance (myocardial R, arteriolar R, epicardial R)

Question 7

list factors that contribute to arteriolar resistance

Answer 7

vascular tone, local metabolites, endothelial function

Question 8

list factors that affect epicardial resistance

Answer 8

atherosclerosis

Question 9

write an equation for calculating coronary blood flow

Answer 9

CBF = (Postium-PCS)/(Rart + Rmyo + REpi)

Question 10

highest flow through the left coronary artery is during early ______

Answer 10

diastole (aortic valve open, muscles not contracting)

Question 11

myocardial resistance is greater in the ____ than in the _________

Answer 11

subendocardium; epicardium

Question 12

arteriolar resistance is adjusted in response to metabolic factors, including…

Answer 12

adenosine, prostaglandins, NO, endothelin, potassium, oxygen

Question 13

explain autoregulation in the context of arteriolar resistance

Answer 13

resistance, R- art, is dynamic and varies in response to local conditions to titrate the blood flow into the local tissue

Question 14

describe coronary flow reserve

Answer 14

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.

Question 15

R-myo is due to compression of the perforating arteries within ventricular muscle in ________.

Answer 15

systole

Question 16

R-epi can become important in the case of ________

Answer 16

atherosclerosis

Question 17

the only way to meaningfully increase oxygen supply to the heart is to increase__________

Answer 17

coronary blood flow

Question 18

what is the primary mechanism of regulating coronary blood flow

Answer 18

alter resistance to flow in coronary arteries (R-art)

Question 19

describe reactive hyperemia and how it relates to coronary flow reserve

Answer 19

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.

Question 20

what compound is considered the primary link between myocardial oxygen consumption and coronary blood flow

Answer 20

adenosine

Question 21

describe the impact of epicardial stenosis on coronary flow reserve

Answer 21

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

Question 22

most arteriolar reserve is lost at around ____% stenosis, and coronary blood flow becomes strictly dependent on ____________

Answer 22

90%; perfusion pressure

* there will be ischemia at rest

Question 23

list mechanisms of increased myocardial oxygen demand

Answer 23

increased heart rate, increased contractility, increased ventricular wall stress

Question 24

list mechanisms of decreased myocardial oxygen supply

Answer 24

ex in anemia, low coronary perfusion pressure, increased perssure in coronary sinus, reduced arterial oxygen saturation, atherosclerotic plaque rupture with thrombus, endothelial dysfunction

Question 25

CAD leads to limited coronary blood flow by:

Answer 25

fixed narrowing, endothelial dysfunction, increased R-epi

Question 26

list initial cellular effects of ischemia

Answer 26

- 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

Question 27

list effects of opening the K-ATPase channel

Answer 27

loss of potassium gradient, contractile dysfunction. likely self-protective mechanism allowing cell to survive transient periods of ischemia

Question 28

later cellular effects of ischemia

Answer 28

- 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 -

Question 29

list electrical and mechanical effects of ischemia

Answer 29

electrical: dysfunction of SA/AV nodes, arrhythmias mechanical: impaired muscle relaxation, increases filling pressure, decreases compliance, impaired contraction

Question 30

list four types of myocardial reperfusion injury

Answer 30

myocardial stunning no reflow reperfusion arrhythmia fatal reperfusion injury

Question 31

define myocardial stunning

Answer 31

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

Question 32

what is the likely cause of no reflow after opening an occluded epicardial artery

Answer 32

edema, destruction of small vascular structures in myocardium

Question 33

what is the role of O2 in reperfusion injury

Answer 33

oxygen radicals injure cells, reduce NO

Question 34

what is the role of calcium in reperfusion injury

Answer 34

Abrupt rise in intracellular Ca++ is caused by damage to sarcolemmal membrane and SR High Ca++ leads to myocyte hypercontracture, increasing O2 demand

Question 35

describe the phenomenon of ischemic pre-conditioning

Answer 35

people with previous "stuttering angina" have smaller MIs | likely involves the K-ATP channel

Question 36

list clinical effects of ischemia

Answer 36

- 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

Question 37

differentiate between myocardial stunning and hibernating myocardium

Answer 37

- 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

Question 38

what diagnostic study is best to clarify chest pain

Answer 38

history

Question 39

what diagnostic study is best to clarify cellular electrical changes

Answer 39

ECG, stress ECG

Question 40

what diagnostic study is best to clarify reduction in coronary blood flow

Answer 40

myocardial perfusion stress test, coronary angiography, stress echocardiogram, stress MRI

Question 41

what diagnostic study is best to clarify conversion to anaerobic metabolism

Answer 41

PET scan

Question 42

what diagnostic study is best to clarify systolic dysfunction/ impaired contractility

Answer 42

echocardiogram, MRI, CT, physical exam

Question 43

what diagnostic study is best to clarify diastolic dysfunction/ impaired relaxation

Answer 43

echocardiogram, MRI, physical exam