PRECONDITIONING IN RAT HEARTS IS INDEPENDENT OF MITOCHONDRIAL F1F0 ATPASE INHIBITION

Mitochondrial F1F0 adenosinetriphosphatase (ATPase) is responsible for the majority of ATP synthesis during normoxic conditions, but under i schemic conditions it accounts for significant ATP hydrolysis. A previ ous study showed that preconditioning in isolated rat hearts is mediat ed by inhibition of this ATPase during ischemia. We tested this hypoth esis in our isolated rat heart model of preconditioning. Preconditioni ng was accomplished by three 5-min periods of global ischemia separate d by 5 min of reperfusion. This was followed by 20 min of global ische mia and 30 min of reperfusion. Preconditioning significantly enhanced reperfusion contractile function and reduced lactate dehydrogenase rel ease but paradoxically reduced the time to onset of contracture during global ischemia. Myocardial ATP was depleted at a faster rate during the prolonged ischemia in preconditioned than in sham-treated hearts, which is consistent with the reduced time to contracture. ATP during r eperfusion was repleted more rapidly in preconditioned hearts, which i s consistent with their enhanced contractile function. Preconditioning significantly reduced lactate accumulation during the prolonged ische mia. We were not able to demonstrate that mitochondrial F1F0 ATPase (m easured in submitochondrial particles) was inhibited by preconditionin g before or during the prolonged ischemia. The mitochondrial-ATPase in hibitor oligomycin significantly conserved ATP during ischemia and inc reased the time to the onset of contracture, which is consistent with inhibition of the mitochondrial ATPase. Our results show that precondi tioning in rat hearts can be independent of mitochondrial ATPase inhib ition as well as ATP conservation.