Fatty Acid Oxidation Is Preserved Regardless of Impaired Uptake in the Chronically Failing Rat Heart

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Fatty acid is used as a major fuel in the fasting heart, but the precise metabolism in the failing heart remains unknown. We assessed the hypothesis that the fatty acid metabolism might be impaired or delayed during heart failure. We examined in vivo kinetics of an isotope-labeled fatty acid analogue and its substrates as well as hemodynamic parameters and histopathological findings in a rat model of postmyocarditic dilated cardiomyopathy. Rat experimental autoimmune myocarditis (EAM) was induced by injection with porcine cardiac myosin. Rats were treated with quinapril, an angiotensin-converting enzyme inhibitor or vehicle, from the 28th day after healing of myocarditis until the 60th day. On the 61st day, or the compensated chronic heart failure phase, rats were injected with β-methyl-iodophenylpentadecanoic acid (BMIPP) and 15-(p-iodophenyl)-9-methylpentadecanoic acid ([I^<125>] 9MPA), then sacrificed 3, 10, 30, and 60 min later. The hearts were excised, their radioactivities were calculated, and the homogenates were assayed quantitatively on thin layer chromatography. Left ventricular weight was found to increase by 1.6-times and the myocardial area of fibrosis was prominent in chronic heart failure rats. Myocardial uptake of BMIPP and 9MPA decreased by 48～75% in the failing heart; however, the final oxidized product ratio of total 9MPA substrates, p-iodophenylacetic acid (PIPA), increased by 127～136% compared with the normal heart. Quinapril decreased the central venous pressure and left ventricular enddiastolic pressure, but increased the absolute value of the rate of isovolumetric contraction. Quinapril suppressed left ventricular hypertrophy by 70% and decreased the fibrosis area by 35% in this model. Quinapril also improved the initial uptake of fatty acid into the myocardium, but it did not affect the substrate pattern of 9MPA metabolites. Our findings suggest that fatty acid oxidation is preserved regardless of impaired uptake in the chronically failing rat heart and that quinapril is able to correct the uptake of fatty acid into the myocardium.

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