ADENOSINE SLOWS ISCHEMIC METABOLISM IN CANINE MYOCARDIUM INVITRO - RELATIONSHIP TO ISCHEMIC PRECONDITIONING

Objective: Studies in rabbits suggest that the cardioprotective effects of adenosine against lethal cell injury may be related to production of adenosine and subsequent activation of adenosine A1 receptors. However, it is not known whether intracoronary adenosine therapy can mimic the metabolic sparing effects of preconditioning in rabbits or dogs. The purpose of this study was to determine the effect of intracoronary adenosine on ischaemic metabolism in totally ischaemic canine myocardium. Methods: Dog hearts (n=13) were excised and the coronary arteries were perfused with an oxygenated Krebs' buffer containing glucose. Adenosine was added to the buffer perfusing the circumflex (treated) region. Following perfusion, control and treated beds from each heart were subjected to 90 min total ischaemia at 37-degrees-C. Tissue levels of ATP and glycolytic intermediates were determined at several time points during the ischaemic incubation. Results: Adenosine significantly slowed the rate of ATP depletion, glycogen utilisation, and lactate accumulation during the first 20 minutes of total ischaemia. Conclusions: The results suggest that adenosine is capable of slowing ischaemic metabolism and they are consistent with the hypothesis that adenosine may mediate ischaemic preconditioning.