A role of fatty acid oxidation in cardiac hypertrophy.
Following a myocardial infarction the patient with a dilated heart is at greater risk for arrhythmias, congestive failure and sudden death. Studies of myocardial infarction in experimental animals have shown that, with infarcts involving up to 20% of the left ventricle, hypertrophy of surviving myocytes occurs and there are minimal hemodynamic changes. Infarctions greater than 20% induce little additional hypertrophy, and develop increased left ventricular filling pressures and cardiac dilatation. It has been suggested that inadequate hypertrophy of residual myocardium may be a reason for the progressive left ventricular dilatation which occurs after large myocardial infarcts. There are data in humans and animals suggesting that the mass of the left ventricle following a myocardial infarction correlates with improvement in systolic function. Studies from our laboratories have previously shown that 2-tetradecylglycidic acid, an inhibitor of carnitine palmitoyl transferase I, inhibits mitochondrial long-chain fatty acid oxidation and causes myocardial hypertrophy when given to rats by mouth for 7-28 days. We carried out studies to see whether induction of additional myocardial hypertrophy by means of feeding tetradecylglycidic acid might prevent pathologic dilation following a large (50%) infarct in rats. Treatment of control and infarcted rats with tetradecylglycidic acid for 10 days resulted in myocardial hypertrophy in both groups. The rats with myocardial infarction treated with tetradecylglycidic acid had an increase in peak developed left ventricular pressure during abrupt aortic occlusion and lower left ventricular end-diastolic volumes, when compared to untreated rats with myocardial infarction, while the stroke volume was maintained. Thus induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of left ventricular dilatation and had beneficial effects on systolic function following a large myocardial infarction.
Bressler
R
R
Department of Medicine, University of Arizona Health Sciences Center, Tucson.
Goldman
S
S
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D004852:Epoxy Compounds; D005227:Fatty Acids; D005947:Glucose; C021756:2-tetradecylglycidic acid