Endogenous adenosine increases O₂ utilisation efficiency in isoprenaline-stimulated canine myocardium

Objective: We have previously demonstrated that myocardium is capable of down-regulating its O₂ requirements and thus avoiding ischaemia when O₂ supply is limited. The present study tested the hypothesis that endogenous adenosine produced this protective response when O₂ supply was decreased by moderate coronary hypoperfusion or moderate coronary hypoxaemia. Methods: In anaesthetised dogs, heart were exposed by left thoracotomy and instrumented for measuring intraventricular pressure and regional myocardial segment length. The left anterior descending coronary artery was isolated, cannulated, and extracorporeally perfused. Coronary O₂ supply was moderately reduced by lowering coronary perfusion pressure from 100 to 60 mmHg or by lowering coronary arterial O₂ content by 50%. Hearts were treated with intracoronary infusions of adenosine, adenosine deaminase to degrade endogenous adenosine or with erythro-9-(2-hydroxy-3-nonyl)-adenine·HCl (ENHA) to inhibit adenosine degradation by endogenous adenosine deaminase, during B-adrenergic stimulation with isoprenaline. Cardiac power in the left anterior descending perfusion territory was indexed by the product of heart rate·left ventricular peak systolic pressure·percent systolic segment shortening. O₂ utilisation efficiency was taken as the ratio of power index/myocardial O₂ consumption. Results: Prior to a reduction in O₂ supply, isoprenaline did not alter O₂ utilisation efficiency. Intracoronary adenosine increased O₂ utilisation efficiency during isoprenaline stimulation by 23% (p < 0.05). EHNA slightly increased O₂ utilisation efficiency during isoprenaline stimulation (10%; P < 0.05); adenosine deaminase was without effect. When coronary perfusion pressure was decreased, adenosine deaminase sharply lowered cardiac power and O₂ utilisation efficiency during isoprenaline stimulation, whereas EHNA augmented isoprenaline-enhanced power and increased efficiency. During hypoxaemia, adenosine deaminase lowered regional power but not efficiency during isoprenaline infusion; EHNA did not affect power but lowered O₂ consumption and increased efficiency. Myocardial lactate extraction and contractile function during isoprenaline stimulation were not attenuated by reduced O₂ supply, indicating that myocardial ischaemia did not occur under these conditions. Conclusion: Endogenous adenosine increases myocardial O₂ utilisation efficiency during β-adrenergic stimulation, and thus helps avert ischaemia when myocardial O₂ supply is reduced.