Brief Increase in Carbohydrate Oxidation After Reperfusion Reverses Myocardial Stunning in Conscious Pigs

Abstract

BACKGROUND: Previous studies have examined only acute effects of enhanced glucose oxidation on postischemic myocardium. The goal of the present study was to examine prolonged functional recovery subsequent to postischemic, intracoronary pyruvate dehydrogenase kinase inhibition with dichloroacetate (DCA) of stunned myocardium in conscious pigs. METHODS AND RESULTS: Myocardial stunning was induced in conscious pigs by coronary stenosis, ie, 40% reduction of coronary blood flow for 90 minutes, followed by full reperfusion. After the initial peak, but during early reactive hyperemia (5 minutes of reperfusion), 1 hour of intracoronary infusion at 20% of measured coronary blood flow was begun using 20 mmol/L [2-(13)C]glucose without (n=4) or with (n=5) 20 mmol/L DCA. Coronary stenosis resulted in similar reduction in wall thickening in both untreated (-53+/-3% from 3.27+/-0.22 mm, n=9) and DCA (-51+/-3% from 3.08+/-0.15 mm, n=5) groups. During reperfusion, DCA increased glucose oxidation 10-fold. In the absence of DCA, myocardial stunning was observed; ie, wall thickening was reduced by 48+/-3% at 1 hour of reperfusion and did not fully recover for 48 hours. In contrast, in DCA pigs, myocardial stunning was ameliorated (P<0.05). CONCLUSIONS: Transient metabolic intervention within a clinically relevant time after ischemia eliminates myocardial stunning in conscious pigs during augmented carbohydrate oxidation and provides sustained benefits in contractile recovery.