Metabolic changes in heart homogenate of Syrian hamsters with hereditary cardiomyopathy (BIO 14.6 strain) were examined. Oxidation of labeled fatty acids and acetate by myopathic homogenates was severely depressed; CO 2 production from labeled acetate was only one-fifteenth of the control value, and butyrate oxidation was suppressed to one-fourth of the control value. Although the addition of carnitine enhanced the oxidation of palmitate and octanoate by homogenates from both healthy and cardiomyopathic hamsters, the magnitude of the depression of oxidation (60-80%) in the myopathic homogenates was not influenced by carnitine. No change occurred in the rate of formation of palmitoyl-CoA from palmitoyl-
l-carnitine or in the activity of acyl-CoA synthetases; similarly, the one-step oxidation of [1- 14 C]pyruvate, [1- 14 C]α-ketoglutarate, and succinate was unimpaired in cardiomyopathy, and the oxidation of [2- 14 C]pyruvate and [U- 14 C]α-ketoglutarate was maintained at a relatively high level (63-71% of control). In contrast, oxidation of [1, 4- 14 C]- and [2, 3- 14 C]succinate and [1- 14 C]acetyl-CoA by the myopathic homogenates was depressed to only 40% of the control values. The mechanism responsible for these defects in substrate oxidation by tissue homogenates from cardiomyopathic hearts has not been elucidated; however, significant increases in the activities of two of five hydrolytic enzymes indicate the possible involvement of lysosomes. Ventricular RNA and DNA, the ratio of RNA to DNA and the ratio of heart weight to body weight were all significantly increased, but myocardial water and triglyceride content and esterification of [1- 14 C]palmitate into neutral lipids showed no significant change.