Role of cellular energy state and adenosine in the regulation of coronary flow during variation in contraction frequency in an isolated perfused heart

Abstract

Regulation of coronary flow as a function of myocardial energy expenditure was investigated in isolated perfused rat hearts electrically paced at the desired frequencies. The sinoatrial node was excised to lower the endogenous heart rate. The main covariants measured were phosphagen, inorganic phosphate, adenosine, inosine and hypoxanthine concentrations in the tissue, washout of nucleosides and hypoxanthine into the perfusate, oxygen consumption and coronary flow. Oxygen consumption was linearly correlated with heart rate and coronary flow, while the correlation between coronary flow and perfusate adenosine was nonlinear. The adenosine concentrations in the tissue and perfusate showed a mirror image curvilinearity reminiscent of a threshold pattern for adenosine washout. The tissue adenosine content had a negative linear correlation with the adenylate phosphorylation potential (long(ATP/ADP X Pi)). Adenosine output was linearly correlated with free AMP concentration in the tissue, the latter being calculated from the equilibrium of the adenylate kinase reaction. The results confirm the correlation between cellular energy state and coronary flow and support the notion that the mediators between the former and the vascular smooth muscle involve the concentration of free AMP in the tissue, suggesting that the formation of adenosine may be limited by the availability of AMP. The results are in agreement with the hypothesis that adenosine is the diffusible extracellular mediator in the energy-linked regulation of coronary flow.