Published Online
on November 11, 2002

A more recent version of this article appeared on November 26, 2002

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Submitted on July 29, 2002
Revised on August 28, 2002
Accepted on September 2, 2002

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

Raymond K. Kudej DVM, PhD, Lawrence T. White BS, Amelia B. Kudej BS, Stephen F. Vatner MD, and E. Douglas Lewandowski PhD^*

From the Program in Integrative Cardiac Metabolism, Departments of Physiology and Biophysics (L.T.W., E.D.L.) and Medicine (Cardiology) (E.D.L.), University of Illinois at Chicago College of Medicine; and Cardiovascular Research Institute (R.K.K., A.B.K. S.F.V.), Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, Newark. Dr Kudej is currently at Tufts University School of Veterinary Medicine, North Grafton, Mass.

^* To whom correspondence should be addressed. E-mail: dougl{at}uic.edu.

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 [2-¹³C]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.

Key words: stunning, myocardial • reperfusion • ischemia • glucose

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