RELATION BETWEEN THE O2 SUPPLY - DEMAND RATIO, MVO2, AND ADENOSINE FORMATION IN HEARTS STIMULATED WITH INOTROPIC AGENTS

Mooted controllers of adenosine formation in heart are the oxygen supply:demand ratio, myocardial oxygen consumption (MVO2), the cytosolic phoshorylation potential (log[ATP]/[ADP][P(i)]. The relationship between these parameters and purine release (adenosine + inosine) into the venous effluent was examined in isovolumic rat hearts perfused at 20 and 12 mL · min-1 · g-1 with a glucose containing crystalloid buffer and stimulated with inotropic agents (isoproterenol, norepinephrine, 3-isobutyl-1-methylxanthine, and ouabain). The oxygen supply:demand ratio and MVO2 were continuously determined using an oxygen electrode to monitor oxygen supply and consumption. The phosphorylation potential was calculated from phosphorus metabolite levels determined by 31P-NMR spectroscopy and HPLC analysis. Left ventricular function was assessed as the rate-pressure product. All inotropic agents increased the rate-pressure product, with increases in function being greater in the hearts perfused at 20 mL · min-1 · g-1. MVO2 was linearly related to the rate-pressure product at each flow rate; however, the hearts perfused at 20 mL · min-1 · g-1 exhibited approximately twofold greater MVO2 values for similar rate-pressure product values. All inotropic agents increased adenosine release into the venous effluent. While there was a significant linear relation between adenosine formation and MVO2 in hearts perfused at both flow rates and stimulated with drugs, the relations differed with adenosine release being approximately fourfold greater in hearts perfused at 12 mL · min-1 · g-1 under similar conditions of MVO2. Adenosine formation correlated exponentially with the ratio of oxygen supply:demand under all conditions (r = 0.97) and the relation did not differ significantly between the hearts perfused at different rates. The phosphorylation potential was decreased from control values by all drugs at both flow rates and plotted linearly with MVO2, although the relations differed between hearts perfused at different rates. Alternatively, the phosphorylation potential plotted linearly with oxygen supply:demand under all conditions (r = 0.98) and did not differ at different flow rates. These results support the idea that adenosine formation depends on the oxygen supply:demand ratio and indicate that MVO2 is not a consistent index of adenosine formation in the glucose-perfused isolated rat heart. The oxygen supply:demand ratio is reflected in the cytosol by changes in the cytosolic phosphorylation potential.