Effect of pyruvate on regional ventricular function in normal and stunned myocardium

The prolonged ventricular dysfunction following brief periods of coronary artery occlusion that does not produce irreversible damage has been termed the "stunned" myocardium. Although ventricular function returns to preischemic values by 1 to 7 days after reperfusion is established, inotropic therapy may be necessary to enhance contractility in the stunned heart. The purpose of this study was to determine the effect of pyruvate on ventricular function in normal and stunned myocardium. Eight chloralose/urethane anesthetized dogs were instrumented with ultrasonic crystals to measure systolic wall thickening in the left anterior descending artery (LAD) and left circumflex artery perfused regions of the left ventricle. Pyruvate (1 ml/min of 150 mM sodium pyruvate, pH 7.4) was infused directly into the LAD prior to and 30 minutes after a 10 minute LAD occlusion. Prior to LAD occlusion, LAD pyruvate infusion increased systolic wall thickening in the LAD-perfused region from 16.2% +/- 4.3% to 23.4% +/- 5.1% (p less than 0.05). Thirty minutes after LAD occlusion, regional wall thickening was depressed (3.3% +/- 2.6%; p less than 0.05), which is indicative of stunned myocardium. Subsequent LAD pyruvate infusion increased wall thickening in the stunned myocardium to 12.7% +/- 2.5%. The improvement of regional ventricular function was maintained only during the pyruvate infusion, as function returned to prepyruvate levels within 20 minutes after cessation of pyruvate infusion. These data indicate that pyruvate exerts a positive inotropic effect in normal and stunned myocardium. If pyruvate, a key intermediate in energy-producing pathways, exerts its inotropic effect through an enhancement of the energy state of the heart, it may have advantages over traditional inotropic agents in the treatment of postischemic contractile dysfunction.