Glucose and Palmitate Oxidation in Isolated Working Rat Hearts Reperfused After a Period of Transient Global Ischemia

• Published in: Circulation research Vol. 66; no. 2; pp. 546 - 553
• Main Authors: Lopaschuk, Gary D, Spafford, Marguerite A, Davies, Norman J, Wall, Stephen R
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.02.1990; Lippincott
• Subjects: Animals; Biological and medical sciences; Coronary Disease - metabolism; Coronary Disease - physiopathology; Fatty Acids - metabolism; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Heart; Heart - physiopathology; In Vitro Techniques; Male; Myocardial Reperfusion; Myocardium - metabolism; Oxidation-Reduction; Palmitates - metabolism; Palmitic Acids - metabolism; Rats; Rats, Inbred Strains; Triglycerides - metabolism; Vertebrates: cardiovascular system; Heart; Energy metabolism; Rat; Rodentia; Glucose; Palmitic acid; Fatty acids; In vitro; Recovery; Vertebrata; Mammalia; Reperfusion; Ischemia; Carbohydrate; Oxidation; Circulatory system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.66.2.546

Alterations in energy substrate utilization during reperfusion of ischemic hearts can influence the functional recovery of the myocardium. Energy substrate preference by the reperfused myocardium, however, has received limited attention. Therefore, we measured oxidation rates of glucose and palmitate during reperfusion of ischemic hearts. Isolated working rat hearts were perfused with 1.2 mM palmitate and 11 mM [C] glucose, 1.2 mM [C] palmitate and 11 mM glucose, or 11 mM [C]glucose alone, at an 11.5 mm Hg preload and 80 mm Hg afterload. Hearts were subjected to 60-minute aerobic perfusion or 25-minute global ischemia followed by 60-minute aerobic reperfusion. Steady-state oxidative rates of glucose or palmitate were determined by measuring CO2 production. In hearts perfused with glucose alone, oxidative rates during reperfusion were not significantly different than nonischemic hearts (1,008±335 vs. 1,372±117 nmol [C]glucose oxidized/min/g dry wt, respectively). In the presence of palmitate, glucose oxidation was markedly reduced in reperfused and nonischemic hearts (81±11 and 101±15 nmol [C]glucose oxidized/min/g dry wt, respectively). Palmitate oxidation rates were not significantly different in reperfused compared with nonischemic hearts (369±55 and 455±50 nmol [C]palmitate oxidized/min/g dry wt, respectively). [C]Palmitate was incorporated into myocardial triglycerides to a greater extent in reperfused ischemic hearts than in nonischemic hearts (26.0 and 13.8, mol/g dry wt, respectively). Under the perfusion conditions used, palmitate provided over 90% of the ATP produced from exogenous substrates. Addition of the carnitine palmitoyltransferase I inhibitor, ethyl 2-[6-(4-chlorophenoxy)hexyl]-oxirane-2-carboxylate (Etomoxir, 10 M), during reperfusion stimulated glucose oxidation and improved mechanical recovery of ischemic hearts. These data demonstrate that, as under aerobic conditions, fatty acids are the preferred substrate of reperfused ischemic myocardium. However, increasing glucose oxidation during reperfusion can improve the functional recovery of the myocardium.