Heart bioassay of effluent of isolated, perfused guinea pig hearts to examine the role of metabolites regulating coronary flow during hypoxia

Summary

The concentrations of adenosine and other metabolic factors are known to be altered in the effluent of hypoxic hearts, but the relative contribution of these factors in elevating coronary flow has not been clarified. Langendorff prepared guinea pig hearts were perfused at constant pressure and were made mildly hypoxic so that flow increased but oxygen consumption remained unchanged. When the effluent of these hearts was reoxygenated and pH conrrected and directed to perfuse similarly prepared recipient (bioassay) hearts, flow remained unchanged in recipient hearts. However, when donor hearts were made severely hypoxic so that oxygen consumption decreased, and recipient hearts were perfused at constant flow, the$P_{O_2 }$, pH corrected effluent produced a large vasodilation in recipient hearts. This response was greatly attenuated in the presence of excess adenosine deaminase but completely abolished by theophylline. Thus the apparent loss of adenine compounds into the effluent may account for vasodilation during severe hypoxia, but not during mild hypoxia, if effluent levels of these compounds truly reflect perivascular levels.