Preconditioning-induced attenuation of purine metabolite accumulation during ischemia: memory and multiple cycles

Brief myocardial ischemia (ISC) is known to attenuate purine metabolite accumulation in the interstitial fluid (ISF) during subsequent ISC. We determined how this attenuated purine accumulation was altered by 1) extended reperfusion (REP) and 2) multiple cycles of brief ISC. Microdialysis probes were used to assess ISF levels of the purine metabolites adenosine, inosine, and hypoxanthine in anesthetized rabbits. In one series of experiments, two 10 min periods of regional ISC were separated by 10 (n = 6), 60 (n = 6), or 180 (n = 6) min of REP. In the 10, 60, and 180 min REP groups the increase in ISF purine metabolites during the second ISC was 47%, 55%, and 53% of that seen during the first ISC, respectively. In a second series of experiments, hearts were exposed to 120 min of ISC with (n = 6) or without (n = 6) five preceding cycles of transient ISC (10 min ISC; 10 min of REP). The increase in ISF purine metabolites during the multiple cycles of ISC was progressively attenuated, and there was a delay but eventual increase in ISF purine metabolites during the 120 min ISC. These data demonstrate that attenuated purine metabolite accumulation 1) is progressively greater with multiple cycles of brief ISC, 2) has a memory time of at least 180 min, and 3) is not due to high energy phosphate depletion.