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

Robert T. Mallet, Shang Chiun Lee, H. Fred Downey

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Abstract

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.

Original languageEnglish
Pages (from-to)102-116
Number of pages15
JournalCardiovascular Research
Volume31
Issue number1
DOIs
Publication statusPublished - 1 Jan 1996

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Keywords

  • Adenosine
  • Catecholamines
  • Lactate
  • Myocardial function
  • Myocardial hypoxia
  • Oxygen uptake

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