Mitochondrial inner membrane enzyme defects in porcine myocardial ischemia.
Left anterior descending coronary artery occlusion in anesthetized pigs produced a stable transmural ischemia characterized by a rapid and then sustained loss of blood flow and mechanical function. After 2 h of occlusion, mitochondria from the ischemic area exhibited a 36 +/- 6% drop in state 3 respiratory activity (QO2) supported by the NAD-linked substrates, glutamate plus malate, but only a 5 +/- 3% decrease in QO2 with succinate plus rotenone. The activity of electron transfer complex I (NADH-CoQ reductase) decreased commensurately by 33 +/- 4% with the decrease in QO2 with NAD-linked substrates. Consistent with the nearly unchanged QO2 with succinate plus rotenone, the activities of electron transfer complexes III and IV decreased only slightly by 9 +/- 5% and 9 +/- 4%, respectively. Mitochondrial ATPase (complex V) activity decreased by 48 +/- 2% with little change in its oligomycin sensitivity. A 48% drop in ATPase activity was shown, by means of oligomycin titrations, to correspond to a 32% decrease in NAD-linked substrate supported QO2. The decreases observed in NADH-CoQ reductase and ATPase activities each account nearly quantitatively for the impaired mitochondrial phosphorylating respiration observed during sustained myocardial ischemia. These results suggest that mitochondrial inner enzyme complexes I and V are important sites of cellular injury in myocardial ischemia.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000201:enzymology*; D005260:Female; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone); D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D011808:Quinone Reductases / Q000378:metabolism*; D012039:Regional Blood Flow; D013552:Swine / Q000502:physiology
D009840:Oligomycins; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D000251:Adenosine Triphosphatases