Myocardial Ischemia Flashcards
Discuss causes of myocardial ischemia in the context of oxygen supply and demand
• Increased demand:
o Increased HR, contractility, and/or ventricular wall stress
• Reduction/limitation of peak myocardial O2 supply
o Anemia, low coronary perfusion pressure, increased pressure in coronary sinus, reduced arterial oxygen saturation, atherosclerotic plaque rupture with associated thrombus and endothelial dysfunction and/or coronary vasospasm
Describe the cellular changes that occur as a result of ischemia
• Aerobic metabolism slows
o Decreased ATP production
o Initially (~15 min) ADP + Creatine Phosphate supply ATP
o Later, loss of ATP slows Na+/K+ ATPase
o ATP>ADP>AMP>Adenosine
• Anaerobic metabolism
o Increases lactic acid → decrease in pH
• Cell dysfunction and injury
• Cell death and rupture as cell membrane loses integrity
o Releases enzymes and proteins into blood stream:
• Creatinine kinase
• Troponin
• Cellular protection occurs:
o K(ATP) channels open as pH drops
o Results in initial hyperpolarization
o With continuous opening: cell membrane ion gradients discharge
• Bad: reduces local cellular force of contraction
• Good: results in relative self preservation
Reperfusion Injury
o Paradox: most of cellular injury occurs at reperfusion
o O2 = oxygen radicals injure cells, reduce NO
o Calcium: abrupt rise in intracellular Ca2+ from damaged sarcolemmal membrane and SR (from oxidative stress)
• Result: myocyte hypercontraction → increased O2 demand
o pH: rapid return of normal pH facilitates hypercontracture
• K(ATP) channels close again, removing local protection
o Mitochondrial permeability transition pore
• Opens and collapses membrane gradient
• Uncouples oxidative phosphorylation → loss of ATP production
o Results of reperfusion injury
• Stunning
• No reflow (microvascular injury)
• Poor flow of contrast down an artery
• Seen in cath lab after opening an occlusion
• Causes:
o Vascular occlusion due to debris
o Vascular constriction in response to debris
o Destruction of ischemic tissues
o Tissue edema
• Impact: limits flow after epicardial artery is opened; marker of worse outcome
• Reperfusion arrhythmias (especially accelerated ventricular arrhythmias)
• Myocyte death replaced by fibrotic scar
Discuss how these cellular changes in ischemia result in disturbances in cardiac mechanical and electrical function.
• Electrical changes:
o Dysfunction of sinus and/or AV nodes
o Changes in conduction velocity → arrhythmias
• Changes in pump function
o Impaired relaxation → increased filling pressures (decreased compliance)
• May hear S4 from reduced ventricular compliance
o With time → impaired contraction
Explain the cause and clinical significance of stunned myocardium and hibernation
• Stunning
o From prolonged ischemia ~20 minutes
o Restoration of blood flow
o Alterations in troponin (a myofilament) from impaired Ca2+ response
o Presents as ventricular dysfunction
o Cellular self repair over 7-14 days recovers function
• Hibernation
o Chronic partial occlusion can result in depressed ventricular contractility
o Reduced function but myocytes still alive
o Will recover function if blood flow improves
o Identifying “viability” can be clinically important
Relate the following diagnostic tests to the manifestations of myocardial ischemia– electrocardiogram, echocardiogram, nuclear perfusion study, PET scan.
• Ischemia occurring at rest
o Electrical impact → ECG → ST segments
o Wall function imaging → ECG, ventriculogram
o Relative perfusion imaging → nuclear
o Anatomic evaluation → CT scan, angiogram, ECG, MRI
• Ischemia only induced by stress
o Exercise + ECG +/- Echo or nuclear
o Vasodilator + nuclear image
o Beta agonist (to stimulate stress) + Echo
Discuss the determinants of myocardial oxygen supply
O2 supply = CBF x (O2%sat, art – O2%sat, cs)
o Oxygen content
• Hemoglobin level
• Oxygen saturation
o Oxygen extraction
• Maximized in heart
• O2 saturation in coronary sinus = 25-35%
• So to increase O2, need to increase CBF
o Coronary blood flow (CBF) = (Postium – Pcs)/(Rart + Rmyo + Repi)
• Coronary perfusion pressure
• Postium: pressure at opening of vessel; varies with cardiac cycle
• Pcs: pressure at coronary sinus, generally low & same as atrial P
• Coronary resistance:
• Myocardial R: perforating vessels;
o Cyclic muscular compression
o Greater resistance in subendocardium than subepicardium vessels (ventricular hypertrophy enhances gradient)
o Greater impact in left coronary than right (has more flow in diastole)
• Arteriolar R (affected by autoregulation: vascular tone, local metabolites, endothelial function)
o Metabolites: adenosine, prostaglandins, NO, endothelin, K+, O2
o CFReserve is the ability of Rart to drop more
• Low CFR limits peak supply
• Epicardial R (normally zero, but higher if atherosclerosis)
o As Repi increases, Rart decreases to match → CFReserve decreases as Repi increases
Discuss the determinants of myocardial oxygen demand
o Myocardial contractility
• Increased by SNS stimulation
• Increased contractility → increases energy heart uses, so need more oxygen
o Heart rate
• Directly related to O2 consumption
o Wall stress
• Three variables: BP, ventricular radius, wall thickness
• WS = (BP x LV radius) / (2 x wall thickness)
Explain the impact of the cardiac cycle on coronary blood flow
• Heart contracts → compresses its own arteries
• Systole:
o Rmyocardial increases relative to diastole → reduces CBF
o Coronary ostial Pressure increases → increases CBF
o In left ventricle: increased resistance outweighs higher pressure → flow into myocardium to be greater in diastole
• Myocardial compression in systole:
o Greater toward inner edge (endocardium) than outer (epicardium)
o Enodcardial myocytes contracting AND being squeezed by cells further out
o With greater compression → subendocardium at greater risk for ischemia
Explain the concept of coronary flow reserve.
• Heart modifies Rart to maintain local control over average rate of blood flow
• Uses lowest possible blood flow rates to meet O2 needs → efficient
• When increased O2 demand = heart increases CBF
• Ability to increase flow related to ability to decrease Rart
o If arterioles not maximally dilated → some coronary flow reserve remains
• Experimentally demonstrate with reactive hyperemia in lab setting
o Represents amount of available coronary flow reserve
Discuss the impact of epicardial stenosis on coronary flow reserve.
• Normal/healthy heart: Repicardial is negligible
• With CAD and atherosclerosis: Repi increases → flow will drop if keep same pressure
• To maintain flow rates→ decrease Rart so total coronary resistance stays same
• Cost: uses up coronary flow reserve
• At about 75% stenosis: most arteriolar reserve is lost
o CBF dependent on perfusion pressure
• At about 90% stenosis:
o CBF can be reduced even at rest → resting ischemia
