Phasic Release of Adenosine during Steady State Metabolic Stimulation in the Isolated Guinea Pig Heart

If adenosine is the major factor responsible for myocardial metabolic vasodilation, its release should be sustained as long as oxygen consumption and coronary flow are augmented. To see if adenosine meets this criterion, we examined the time course of its release during norepinephrine infusion in isolated, non-working guinea pig hearts (n = 8). During an 11-minute infusion period (steady state perfusate concentration = 6 × 10 m), the coronary effluent was collected over 30-second intervals for measurements of coronary flow (ml/min per g), and adenosine and inosine release (pmol/min per g). Myocardial oxygen consumption (MVO2 = μl O2/min per g) was measured at 1, 4, 6.5, and 11 minutes. Control values of coronary flow, myocardial oxygen consumption, and adenosine and inosine release were 7.5 ± 0.4, 85 ± 5, 22 ± 5, and 431 ± 39, respectively. During norepinephrine infusion, coronary flow, myocardial oxygen consumption, and adenosine release attained maximal levels within one minute (inosine within 2 minutes). These values were 10.6 ± 0.4, 125 ± 9, 849 ± 110, and 2595 ± 581, respectively. Thereafter, coronary flow and myocardial oxygen consumption values were sustained. In contrast, adenosine and inosine release significantly declined to nadirs by 9.5 minutes. Thereafter, steady state levels were maintained at 117 ± 24 and 960 ± 294, respectively. Further, evaluation of this response shows first, that the coronary bed can dilate further with infusion of adenosine during norepinephrine infusion; second, that the myocardium releases more adenosine, in a phasic manner, if stimulated with higher concentrations of norepinephrine; third, that the release of adenosine is independent of α-receptor activation (i.e., same responses to norepinephrine occur with prazosin, or isoproterenol); fourth, that there is phasic release of adenosine during stimulation by elevated perfusate calcium concentration; and fifth, that the release of adenosine is dependent upon β-receptor stimulation with catecholamines but not with elevated perfusate calcium. These results suggest that release of adenosine from myocardial cells peaks soon after metabolism is increased, and then wanes. This raises the possibility that adenosine does not maintain sustained metabolic coronary dilation. (Circ Res 53636-643, 1983)