Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts.
Fatty acids in excess impair mechanical function and electrical stability in ischemic hearts. The purpose of the present studies was to test whether oxfenicine, an agent capable of reducing fatty acid metabolism, can prevent these consequences and in so doing improve hemodynamic performance. Two groups of working swine hearts (n = 15), extracorporeally perfused with whole blood, were compared over 90 min of controlled coronary perfusion. An emulsion of triacylglycerols (Intralipid) with heparin were administered systemically to augment serum fatty acids threefold (0.30 to 0.92 mumol/ml). Labeled [U14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Saline (n = 7) or oxfenicine (17-33 mg/kg, n = 8) was administered to placebo or treated animals at 30 min perfusion. 14CO2 production from labeled palmitate was decreased by 55% (P less than 0.025) at normal flows in oxfenicine-treated hearts and was reduced further during ischemia. Tissue levels of acyl carnitine were significantly reduced and acetyl CoA levels significantly increased in oxfenicine-treated hearts both in aerobic and ischemic myocardium. These changes were associated with an improvement in mechanical function. Left ventricular systolic and developed pressures and maximum left ventricular dP/dt were increased by 36 delta %, P less than 0.01; 46 delta %, P less than 0.025; and 41 delta %, P less than 0.025, respectively, at end ischemia as compared with placebo hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010477:Perfusion; D011312:Pressure; D013552:Swine
D005227:Fatty Acids; C023010:4-hydroxyphenylglycine; D005998:Glycine