REGRESSION OF CARDIAC-HYPERTROPHY NORMALIZES GLUCOSE-METABOLISM AND LEFT-VENTRICULAR FUNCTION DURING REPERFUSION

It is not yet known if the alterations in myocardial glucose metabolis m and the exaggerated left ventricular dysfunction that occur during r eperfusion in hypertrophied hearts are reversible. Thus, we studied is olated working hearts from aortic-banded (n = 29) and sham-operated co ntrol (n = 32) male Sprague-Dawley rats with or without enalapril male ate treatment (25.6 +/- 0.8 mg/kg per day, p.o.) to determine the effe ct of regression of cardiac hypertrophy on myocardial glucose metaboli sm and post-ischemic heart function. Hearts were perfused with buffer containing 1.2 mM palmitate, 11 mM [5-H-3]/[U-C-14]-glucose, 0.5 mM la ctate and 100 mu U/ml insulin. Glucose metabolism [rates of glycolysis ((H2O)-H-3 production) and rates of oxidation ((CO2)-C-14 production) of exogenous glucose] and heart function (heart rate x peak systolic pressure) were measured during 30 min pre-ischemic perfusion and 60 mi n of reperfusion following 20 min of global, no-now ischemia. Hearts f rom untreated aortic-banded rats were hypertrophied, being 27.6 +/- 1. 8% larger than hearts from untreated control rats. Enalapril treatment caused regression of cardiac hypertrophy that normalized heart weight in aortic-banded rats. Rates of glycolysis of exogenous glucose in he arts from untreated aortic-banded rats were accelerated compared to ra tes in hearts from untreated control rats during pre-ischemic perfusio n (4391 +/- 97 v 2652 +/- 69 nmol glucose/min per g dry wt, respective ly, P < 0.05) and reperfusion (2402 +/- 58 v 1597 +/- 88 nmol glucose/ min per g dry wt, respectively, P < 0.05), In contrast, rates of glyco lysis of exogenous glucose in hearts from enalapril-treated aortic-ban ded rats were normalized before and after ischemia. Rates of glycolysi s of exogenous glucose in hearts of control rats were not affected by enalapril treatment. Oxidation of exogenous glucose was not different among groups either before or after ischemia. Function of hearts from untreated aortic-banded rats at the end of reperfusion was significant ly less than that of hearts from untreated control rats (23.9 +/- 2.6 v 32.2 +/- 0.7 mmHg x beats per min/1000, respectively, P < 0.05). As with myocardial glucose metabolism, function of hearts from aortic-ban ded rats treated with enalapril was normalized during reperfusion. Thu s, pharmacologically induced regression of pressure-overload cardiac h ypertrophy normalizes glucose metabolism as well as left ventricular f unction during reperfusion. (C) 1997 Academic Press Limited.