EFFLUX OF ADENOSINE AND TOTAL ADENYLATE CATABOLITES DURING ALTERATIONS OF THE CELLULAR-ENERGY STATE - AN NMR-STUDY OF CONTINUOUS AND DISCONTINUOUS ISCHEMIA

Reperfusion after continuous or discontinuous ischemia has a bearing o n clinical interventions. An important question is the washout of meta bolites after periods of diminished energy state of the myocardial cel l. We therefore set out to determine the washout of adenosine and its metabolites after periods of ischemia in an experimental set-up which allowed non-destructive monitoring of the cellular energy state and cy tosolic pH over consecutive time intervals. Isolated rat hearts were p erfused with hemoglobin-free saline in a nuclear magnetic resonance sp ectrometer equipped for P-31 NMR spectroscopy of phosphorus-containing metabolites, which could be measured over 3-min time blocks. The resp onse of the heart when subjected to 18 min of continuous ischemia and subsequent reperfusion was compared with that when subjected to three 6-min periods of ischemia separated by 3-min periods of reperfusion. T he mechanical performance of the hearts, oxygen consumption and efflux of adenosine and its metabolites were measured. The consecutive ische mic periods produced no evidence of preconditioning as judged from the cellular energy state, although the mechanical recovery was better th an after continuous ischemia. During the repetitive ischemia/reperfusi on protocol the efflux of adenosine was smaller, although the efflux o f combined adenylate catabolites did not differ from that after contin uous ischemia. The results do not support the view of adenosine being a major effector in the phenomenon of preconditioning.