Metabolically based treatment of stunned myocardium

Reversible myocardial ischemia is associated with a rapid decrease in contractility and prolonged postischemic ventricular dysfunction, due in part to altered intracellular calcium handling and/or contractile protein dysfunction. The maintenance of intracellular calcium homeostasis and force development by the contractile apparatus are dependent upon the free energy derived from ATP hydrolysis. This energy of hydrolysis is determined by the myocardial phosphorylation potential, an estimate of which can be made from the ratio (CrP)/(Cr) x (P(i)). Results from in vitro and in vivo studies suggest that pyruvate enhances contractility in both normal and stunned myocardium by enhancing myocardial phosphorylation potential. In regionally stunned porcine myocardium, pyruvate infusion increased recovery of regional ventricular function from 33% +/- 4% of preischemic systolic wall thickening to 81% +/- 4% and increased the (CrP)/(Cr) x (P(i)) ratio fivefold from 0.21 +/- 0.04 to 1.05 +/- 0.08. Thus, metabolic substrates that enhance myocardial energetics and ventricular function may be effective agents for attenuating postischemic ventricular function.