Mooted controllers of adenosine formation in heart are the oxygen supply:demand ratio, myocardial oxygen consumption [Formula: see text], the cytosolic phosphorylation potential (log[ATP]/[ADP][Pi]). 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 [Formula: see text] 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. [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] 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 [Formula: see text]. 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 hearts perfused at different rates. The phosphorylation potential was decreased from control values by all drugs at both flow rates and plotted linearly with [Formula: see text], 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 [Formula: see text] 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.Key words: O2 supply:demand ratio, adenosine, crystalloid-perfused rat heart, inotropic agents, myocardial oxygen consumption.
Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study
