PYRUVATE INCREASES THRESHOLD FOR PRECONDITIONING IN GLOBALLY ISCHEMICRAT HEARTS

Isolated rat hearts can be protected by preconditioning, although this has not been found when they are perfused with pyruvate. We addressed the question of whether pyruvate could increase the threshold for pre conditioning in isolated rat hearts and whether this could be overcome with increased durations of ischemia. A protocol of four periods of 5 min of ischemic preconditioning (4 x 5 min) protected hearts (improve d recovery of function, reduced lactate dehydrogenase release) not per fused with pyruvate from a subsequent 30-min period of global ischemia , but did not protect pyruvate-perfused hearts. Pilot studies indicate d that hearts perfused in the presence of pyruvate must be ischemic fo r similar to 40% longer to produce equivalent ischemic damage in nonpy ruvate-treated hearts. Thus the preconditioning period of 5 min was in creased by similar to 40% to 7 min to produce equivalent degrees of pr econditioning. Hearts preconditioned with the 4 x 7 min protocol with pyruvate were significantly protected against a subsequent severe glob al ischemia (enhanced recovery of function, reduced lactate dehydrogen ase release). High-energy phosphates were measured at the end of the p reconditioning protocol (before final global ischemia) to determine wh ether there was a correlation between cardioprotection and high-energy phosphate levels. There was no correlation between ATP, ADP, or AMP l evels and the efficacy of preconditioning. However, an increase in cre atine phosphate was associated with cardioprotection, although the imp ortance of this in mediating preconditioning is doubtful. Thus the abi lity to precondition rat hearts is somewhat dependent on their energy source, but this appears to be due to changes in the severity of the i schemic preconditioning event.