Relationship between myocardial oxygen consumption, coronary flow, and adenosine release in an improved isolated working heart preparation of guinea pigs

Abstract

We describe herein an isolated working heart preparation of guinea pigs, in which coronary perfusion pressure can be varied independently from afterload by directing left ventricular stroke volume into an artificial circulation. This preparation proved to be functionally stable, exhibited hemodynamic features characteristic of the heart in situ, and shows the phenomena of flow autoregulation, reactive hyperemia, and hypoxic and metabolic vasodilation. Myocardial oxygen consumption and coronary flow were tightly coupled when cardiac work was enhanced by either 1.5-6.0 X 10(-9) M isoproterenol (r = 0.975) or changes of afterload (20-100 mm Hg) (r = 0.890). Isoproterenol-induced changes in adenosine release correlated with changes of coronary flow (r = 0.869) and myocardial oxygen consumption (r = 0.894). The concentrations of endogenously formed adenosine were within the vasodilatory range of exogenously applied adenosine. In contrast, afterload-induced changes in myocardial oxygen consumption were not associated with an enhanced release of adenosine, inosine, and hypoxanthine, and did not correlate with coronary resistance (r = 0.422). The specific activity in the effluent perfusate of intracoronarily infused [8-14C]adenosine was increased with elevated afterload, suggesting that less adenosine was liberated by the heart. Our findings indicate that adenosine formed in response to beta-adrenergic stimulation is a major metabolite adjusting coronary flow to myocardial needs. Adenosine, however, does not appear to be involved in the afterload-induced changes in coronary flow when coronary perfusion pressure and, thus, oxygen supply are increased simultaneously. It is likely that formation of adenosine is not triggered by changes in MVO2 as such, but may critically depend on the oxygen supply: demand ratio.