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 pressure (LVGP) was calculated as peak systolic minus end diastolic pressure. Three substrate groups, pyruvate (5 mm), glucose (15 mm) and octanoate (0.5 mm), were employed. Oxidative stress was induced by perfusion with tertiary-butyl hydroperoxide (tBHP. 0.35 mm. 12 min) followed by 25 min of perfusion with control buffer. Hearts perfused with pyruvate showed no significant decrease in contractile function following tBHP treatment (HR × LVGP= 17666 ± 585mmHg/min, initial; 16414±2083 post-tBHP treatment). Glucose-perfused hearts had an intermediate decrease in function (19174±828 mmHg/min, initial; 4379±2083 post-tBHP), while octanoateperfused 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 octanoateperfused hearts (3074±499). Thiobarbituric acid reactive substances (TBARS) were unchanged in hearts perfused with pyruvate (16.2 ± 5 nmoles/g wet wt), but increased significantly in glucose-perfused hearts (36.1 ± 1) and in octanoate-perfused hearts (45.5 ±9). Total glutathione levels were unchanged in hearts perfused with pyruvate (753±68 nmoles/g wet wt), but significantly decreased in glucose-perfused hearts (594±68) and in octanoateperfused hearts (445 ± 38) following tBHP-treatment. Pyruvate significantly reduced 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 from the buffer, while glucose and octanoate were ineffective at removing tBHP.