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

Abstract

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.

Intermittent Adenosine at the Beginning of Reperfusion Does Not Trigger Cardioprotection

“…However, the ADO role in reperfusion is less clear. In fact, it has been shown that preconditioning will greatly attenuate the amount of ADO released during a subsequent ischemic episode [3,34,35]. Moreover, the ADO production during ischemia does not correlate with the protection induced by ischemic or pharmacological preconditioning [4].…”

Targeting nucleotide-requiring enzymes: implications for diazoxide-induced cardioprotection

“…potassium channel openers; mitochondria; ATP-sensitive potassium channel; dehydrogenase ADJUSTMENTS IN CELLULAR ENERGETIC and ionic status are essential in the maintenance of cell tolerance to metabolic stress (11,51,53,60). In cardiac muscle, during an ischemia-reperfusion challenge, adenine nucleotide homeostasis depends critically on the activity of nucleotide-metabolizing enzymes and the extent of tissue oxidative stress closely relates to the rate of dehydrogenase-catalyzed reactions (10,30,40,46,54). Although the nucleotide binding properties and regulatory mechanisms of dehydrogenases and ATPases/ kinases are rather similar (14,21,62), their integral role in cellular protection is poorly understood.…”

Ischaemic preconditioning alters the energy metabolism and protects the ischaemic myocardium in a stepwise fashion

“…In studies of the IP phenomenon, various numbers of ischaemia/reperfusion cycles have resulted in divergent metabolic outcomes as well as different portions of the myocardium at risk being infarcted (Lawson et al 1993, VanWylen 1994, Lasley et al 1995, Iliodromitis et al 1997, Korbmacher et al 2000, Kuzmin et al 2000, Mortimer et al 2000. Differences in the experimental set up and analytical methods are certainly an important factor explaining Acta Physiol Scand 2003, 178, 129-137 Ó 2003 Scandinavian Physiological Society the discrepant results found in these studies.…”