Clinical Pharmacology Research

Our long-term goal is to develop a strategy to decrease the excess myocardial injury in elderly patients following an acute myocardial infarction. We have developed an approach to study this problem in the elderly Fischer 344 rat model. The isolated, buffer perfused elderly heart sustains greater injury after ischemia and reperfusion compared to the adult heart. At baseline, aging-defects in the mitochondrial electron transport chain occur in only one population of heart mitochondrial (interfibrillar) in elderly Fischer 344 rats. Following ischemia there is further damage to the interfibrillar mitochondria. We propose that aging-related defects in mitochondrial oxidative metabolism present at baseline in the elderly heart predispose to a subsequent increase in injury during ischemia compared to the adult heart, and that the decrease in the energy charge and an excess of oxidative damage accounts for the increased in injury observed in the aging heart.