Studies on experimental coronary insufficiency. Effect of L-carnitine on myocardial ischemia produced by sympathetic-nerve stimulation with high plasma fatty acids.
Our previous studies revealed that sympathetic-nerve stimulation (SNSt) plays an important role in the precipitation and the augmentation of myocardial ischemia in dogs with coronary constriction. To clarify the underlying mechanism of the detrimental effect of free fatty acids (FFA) at a high plasma concentration and the beneficial effect of L-carnitine on myocardial ischemia, ischemic changes following SNSt were compared among three groups of dogs with mild or moderate coronary constriction: a saline control group, an intralipid [(IL) 0.1 ml/kg per min + heparin 5 mg/kg] group, and an IL + L-carnitine (200 mg/kg) group. High plasma concentration of FFA aggravated the ischemic changes induced by SNSt in dogs with coronary constriction, in which no signs of increase in myocardial oxygen consumption were seen. L-Carnitine clearly alleviated the mechanical dysfunction, acceleration of anaerobic metabolism, depletion of myocardial contents of high-energy phosphates, myocardial accumulation of lactate, and ECG ischemic changes that were augmented by high plasma FFA in the coronary-constricted dogs with SNSt. From these findings, it was suggested that an increased plasma FFA might aggravate myocardial ischemia, at least, produced by SNSt in dogs with mild or moderate coronary constriction and that L-carnitine might improve the ischemia augmented by FFA, presumably by reducing myocardial accumulation of FFA intermediates.
D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D004562:Electrocardiography; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D006321:Heart / Q000294:innervation*; D006352:Heart Ventricles / Q000503:physiopathology; D006493:Heparin / Q000494:pharmacology; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010710:Phosphates / Q000097:blood; D011188:Potassium / Q000097:blood; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D010710:Phosphates; D019344:Lactic Acid; D006493:Heparin; D011188:Potassium; D002331:Carnitine