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.
