Regional changes in mitochondrial respiration in acute myocardial ischemia. Comparison of the inner and outer heart...

Impairment of mitochondrial respiration in acute myocardial ischemia was studied in the inner and outer layers of canine heart muscle by the determination of oxidative phosphorylation and several respiratory enzymatic activities of isolated mitochondria. As early as 15 min after coronary ligation, the respiratory control ratio decreased as the result of a reduction in the oxygen consumption rate in state 3 to 72% of the control ratio in the inner layer. However, in the outer layer, it dropped to 74% after 1 to 2 hours. The oxygen consumption rate in state 4 and the ADP/O ratio were not significantly altered in both cardiac sublayers. In parallel with a decrease in oxygen consumption rate in state 3, Mg++-dependent ATPase and DNP-stimulated ATPase activities of isolated mitochondria reduced significantly in both sublayers, followed by a sequential increase in Mg++-dependent ATPase activity. Succinate dehydrogenase activity increased in ischemia for 3 hours in the inner layer, and for 6 hours in the outer layer, respectively; cytochrome oxidase activity reduced in both sublayers during the same period. Mitochondrial respiration is impaired in acute myocardial ischemia much earlier in the inner layer by a decrease in oxygen consumption rate in state 3, and there is a chronological delay in the development of ischemic mitochondrial changes in the outer myocardium.