Relationship between hemodynamics during immediate reperfusion and mitochondrial functional recovery in the ischemic myocardium.

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Abstract
Open-chest mongrel dogs [30] were studied to characterize mitochondrial respiration in reperfused myocardium following ischemia induced by left anterior descending coronary artery ligation up to 40 min. Regional myocardial blood flow was measured by the radioactive microspheres, 46Sc (9 .mu.m), during coronary artery occlusion, and 85Sr (9 .mu.m) during reperfusion. Mitochondria were isolated from endocardial and epicardial layers in both nonischemic and ischemic myocardium. Mitochondrial respiration was characterized by a polarographic technique. Cardiac output, stroke volume, left ventricular stroke work and mean arterial pressure were depressed during coronary artery occlusion and they did not improve during 10-20 min of coronary artery reperfusion. Reperfused myocardium following 40 min of coronary artery occlusion increased in myocardial blood flow both in ischemic and non-ischemic tissues. Ratio of phosphorylated ADP to consumed O2 was unchanged. Ischemic endocardial layer following 40 min of coronary artery occlusion showed depression of respiratory control index at the end of 10-20 min of reperfusion. Mitochondrial state-3 respiration was severely depressed when glutamate was added as substrate at the end of coronary artery occlusion. State-3 respiration recovered to normal level during reperfusion in the myocardium rendered ischemic for < 30 min; state-3 respiration was still depressed during 10-20 min of reperfusion following 40 min of coronary artery occlusion. During the reperfusion period, endocardial blood flow was related to mean arterial pressure both in the nonischemic (r = 0.73, P < 0.05) and in the ischemic zone (r ; 0.72, P < 0.05) in hearts ischemic for less than 30 min. Mitochondrial state-3 respiration was not correlated to perfusion pressure in completely reversible (artery ligated < 30 min) myocardium. In ischemic endocardial layer following 40 min of coronary artery occlusion, state-3 respiration was related to perfusion pressure [r = 0.88 (P < 0.02) glutamate substrate; r = 0.92 (P < 0.02) succinate substrate] and to the product of heart rate and mean arterial pressure during 10 min of reperfusion (r = 0.83, P < 0.04). Apparently myocardium can survive up to 30 min of severe ischemia. In partially necrotic myocardium, mitochondrial functional recovery was correlated to mean arterial pressure (perfusion pressure) and cardiac rate pressure product in early reperfusion; coronary blood flow was not correlated to perfusion pressure in this particular phase.