Dichloroacetate stimulates carbohydrate metabolism but does not improve systolic function in ischemic pig heart.
Increased carbohydrate utilization may protect the heart during ischemia and reperfusion. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase, which is the rate-limiting step in oxidation of lactate and pyruvate. The purpose of this study was to determine if the myocardial metabolic changes induced by intracoronary DCA during myocardial ischemia were accompanied by improvement in systolic function. A perfusion circuit was created from the carotid to left anterior descending coronary artery (LAD) in 11 anesthetized Yorkshire swine. Data were obtained under strict hemodynamic control at baseline, after 15 min of moderate (30%) LAD flow reduction, and after an additional 15 min of ischemia with either intracoronary DCA (3 mM, n = 6) or saline (n = 5) infusion. DCA decreased lactate release and increased lactate uptake during ischemia as measured by glucose and lactate carbon-labeled tracers. Despite these metabolic changes, no improvement in systolic shortening, microsphere blood flow, or oxygen consumption occurred. Thus, although DCA stimulated carbohydrate metabolism during myocardial ischemia, it did not directly improve systolic function.
Mazer
C D
CD
Department of Anesthesia, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Cason
B A
BA
Stanley
W C
WC
Shnier
C B
CB
Wisneski
J A
JA
Hickey
R F
RF
D000818:Animals; D050260:Carbohydrate Metabolism; D003326:Coronary Circulation; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005740:Gases / Q000097:blood; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D013599:Systole
D005740:Gases; D012965:Sodium Chloride; D003999:Dichloroacetic Acid