ENDOGENOUS ADENOSINE INCREASES O-2 UTILIZATION EFFICIENCY IN ISOPRENALINE-STIMULATED CANINE MYOCARDIUM

Objective: We have previously demonstrated that myocardium is capable of down-regulating its O-2 requirements and thus avoiding ischaemia wh en O-2 supply is limited. The present study tested the hypothesis that endogenous adenosine produced this protective response when O-2 suppl y was decreased by moderate coronary hypoperfusion or moderate coronar y hypoxaemia. Methods: In anaesthetised dogs, hearts were exposed by l eft thoracotomy and instrumented for measuring intraventricular pressu re and regional myocardial segment length. The left anterior descendin g coronary artery was isolated, cannulated, and extracorporeally perfu sed. Coronary O-2 supply was moderately reduced by lowering coronary p erfusion pressure from 100 to 60 mmHg or by lowering coronary arterial O-2 content by 50%. Hearts were treated with intracoronary infusions of adenosine, adenosine deaminase to degrade endogenous adenosine or w ith erythro-9-(2-hydroxy-3-nonyl)-adenine HCl (EHNA) to inhibit adenos ine degradation by endogenous adenosine deaminase, during beta-adrener gic stimulation with isoprenaline. Cardiac power in the left anterior descending perfusion territory was indexed by the product of heart rat e left ventricular peak systolic pressure percent systolic segment sho rtening. O-2 utilisation efficiency was taken as the ratio of power in dex/myocardial O-2 consumption. Results: Prior to a reduction in O-2 s upply, isoprenaline did not alter O-2 utilisation efficiency. Intracor onary adenosine increased O-2 utilisation efficiency during isoprenali ne stimulation by 23% (P < 0.05). EHNA slightly increased O-2 utilisat ion efficiency during isoprenaline stimulation (10%; P < 0.05); adenos ine deaminase was without effect. When coronary perfusion pressure was decreased, adenosine deaminase sharply lowered cardiac power and O-2 utilisation efficiency during isoprenaline stimulation, whereas EHNA a ugmented isoprenaline-enhanced power and increased efficiency. During hypoxaemia, adenosine deaminase lowered regional power bur not efficie ncy during isoprenaline infusion; EHNA did not affect power but lowere d O-2 consumption and increased efficiency. Myocardial lactate extract ion and contractile function during isoprenaline stimulation were not attenuated by reduced O-2 supply, indicating that myocardial ischaemia did not occur under these conditions. Conclusion: Endogenous adenosin e increases myocardial O-2 utilisation efficiency during beta-adrenerg ic stimulation, and thus helps avert ischaemia when myocardial O-2 sup ply is reduced.