• myocardial ischemia: when the coronary blood flow is insufficient to meet the normal required mechanical work of the myocardium
• can also be a ß in oxygen tension
• myocardial substrate metabolism is dependent on the severity of the ischemia
• complete elimination of flow Þ depletion of phosphates, lactate accumulation, contractile akinesis Þ tissue necrosis and myocardial infarction
• modest reduction to flow (20-60%) Þ ß in myocardial O₂ consumption (10-50%), Ý dependence on anaerobic glycolysis (switch from lactate uptake to lactate production), ß rate of FFA ox (most of ATP comes from this), severe contractile dysfunction
• does not necessarily lead to irreversible tissue damage

• Mild to Moderate Ischemia
• 20-30% reduction in coronary blood flow
• rapid ß in mechanical work, ß in ATP and creatine phosph conc, net output of lactate
• 30-90min: lactate output ß , partial restoration of ATP levels, but contractile output does not return back to normal
• restoration of flow back to normal levels Þ normal contractile function
• this level of ischemia and contract. dysfunction = myocardial "hybernation"
• preserves viability of myocardium by resetting the rate of mechanical work to match the rate of oxygen delivery
• studies show the ß in mechanical function is not due to accelerated anaerobic glycolysis
• MI results in Ý in ability of cardiomyocytes to take up glucose via translocation of glut1 and glut4 into the plasma memb
• Interstitial glucose is ß during ischemia which limits the rate of glucose uptake where there is almost no glucose delivered to the tissue from the blood
• the primary oxidative fuel during mild to moderate ischemia is FA with minor non-oxidative glycolysis and net lactate production
• Severe Ischemia
• >70% reduction in flow
• greater rates of lactate accumulation and glycogen breakdown, severe or complete contractile dysfunction, myocardial necrosis and infarction (with sufficient duration)
• complete block Þ thrombus
• no washout of lactate, intracellular pH ß , ß rate of glycolysis due to H+ inhibition of PFK
• no resynthesis of ATP by OX/PHOS, complete dependence on endogenous substrates, and no wash-out of noxious metabolites (ie H⁺)
• sole source of glycolytic substrate is glycogen
• Demand-Induced Ischemia
• MI is often induced by an insufficient increase in myocardial blood flow in response to an increase in HR, inotropy, afterload, and/or preload that requires an increase in contractile work
• This form of ischemia (ie exercise or pacing) results in Ý in glucose uptake and lactate output

• mitochondrial ox/phos returns to pre-ischemic levels, but contractile work remains imparied
• myocardial stunning: ß contractile power with normal O₂ consumption
• intracellular pH recovers Þ Ý intracell Na Þ activates Na/Ca exchanger Þ Ý intracell Ca Þ Ca overload Þ post-ischemic contractile dysfunction or even death in severe ischemia

• rate of TCA flux and O₂ consumption by the myocardium (MVO₂) µ ventricular power output
• Ý work of heart with short term exercise Þ Ý in gluc, lact and FFA uptake and ß glyco stores
• Ý HR and inotropy Þ Ý mito Ca Þ Ý PDH activity during exercise Þ Ý gluc consumpt
• Ý arterial lactate concentration or ß arterial FFA concentration Þ Ý lactate consumption
• during prolonged exercise, arterial FFA concentration Ý Þ ß flux thru PDH Þ ß gluc and lact oxid.

Angina – blockage Þ Ý acid, ADP, lact, etc; ADP Ý and stimulates pain receptors in heart Þ angina (pain)