ANTIOXIDANT EFFECTS OF PYRUVATE IN ISOLATED RAT HEARTS

Sprague-Dawley rat hearts were perfused under constant flow conditions , and a balloon was inserted into the left ventricle to measure heart rate (HR) and left ventricular pressures. Left ventricular generated p ressure (LVGP) was calculated as peak systolic minus end diastolic pre ssure, Three substrate groups, pyruvate (5 mM), glucose (15 mM) and oc tanoate (0.5 mM), were employed, Oxidative stress was induced by perfu sion with tertiary-butyl hydroperoxide (tBHP, 0.35 mM, 12 min) followe d by 25 min of perfusion with control buffer, Hearts perfused with pyr uvate showed no significant decrease in contractile function following tBHP treatment (HRxLVGP = 17666+/-585 mmHg/min, initial; 16414+/-2083 post-tBHP treatment). Glucose-perfused hearts had an intermediate dec rease in function (19174+/-828 mmHg/min, initial; 4379+/-2083 post-tBH P), while octanoate-perfused hearts recovered no contractile function, Peak release of LDH was lowest in hearts perfused with pyruvate (115/-17 mU/g wet wt/min), intermediate in glucose-perfused hearts (1575+/ -380) and highest in octanoate-perfused hearts (3074+/-499), Thiobarbi turic acid reactive substances (TBARS) were unchanged in hearts perfus ed with pyruvate (16.2+/-5 nmoles/g wet wt), but increased significant ly in glucose-perfused hearts (36.1+/-1) and in octanoate-perfused hea rts (45.5+/-9). Total glutathione levels were unchanged in hearts perf used with pyruvate (753+/-68 nmoles/g wet wt), but significantly decre ased in glucose-perfused hearts (594+/-68) and in octanoate-perfused h earts (445+/-38) following tBHP-treatment, Pyruvate significantly redu ced oxidative injury. In contrast, glucose provided a small reduction in injury while octanoate-perfused hearts had the most severe injury. Measurements of tBHP indicated that pyruvate directly scavenged tBHP f rom the buffer, while glucose and octanoate were ineffective at removi ng tBHP. (C) 1995 Academic Press Limited