Insulin improves functional and metabolic recovery of reperfused working rat heart

Abstract

Background. Glucose, insulin, and potassium solution improves left ventricular function in refractory pump failure. Direct effects of insulin on the heart cannot be determined in vivo. We hypothesized that insulin has a direct positive inotropic effect on the reperfused heart. Methods. Isolated working rat hearts were perfused with buffer containing glucose (5 mmol/L) plus oleate (1.2 mmol/L). Hearts were subjected to 15 minutes of ischemia and reperfused with or without insulin (100 μU/mL) for 40 minutes. Epinephrine (1 μmol/L) was added for the last 20 minutes. Results. Hearts recovered 51.1% of preischemic cardiac power in the absence and 76.4% in the presence of insulin ( p < 0.05). Whereas oleate oxidation remained unchanged, glucose uptake and oxidation increased during reperfusion with epinephrine ( p < 0.01). This increase was significantly greater when hearts were reperfused in the presence of insulin ( p < 0.01). Insulin also prevented an epinephrine-induced glycogen breakdown during reperfusion ( p < 0.05). Conclusions. Insulin has a direct positive inotropic effect on postischemic rat heart. This effect is additive to epinephrine and occurs without delay. Increased rates of glucose oxidation and net glycogen synthesis are more protracted.