Alterations in Fatty Acid Metabolism in Adriamycin Cardiomyopathy

Abstract

Myocardial fatty acid metabolism may be impaired in adriamycin cardiomyopathy. In order to determine the extent of fatty acid metabolism alterations, we measured steady state [ 14C]palmitate oxidation and the incorporation of [ 14C]palmitate into the neutral lipid pool in a rat model of adriamycin cardiomyopathy. Isolated hearts from control rats and rats treated with adriamycin were perfused with 1.2 mmol/l of [ 14C]palmitate for 30 min to achieve steady state oxidation measured as [ 14C]O 2 production: then perfused with 1.2 mmol/l of unlabelled palmitate. Hearts were killed early (0-5 min) or late (10-30 min) after the [ 14C]palmitate perfusion, to determine incorporation into the neutral lipid pool, and neutral lipid pool utilization. In the control group steady state oxidation was reached in 10 min ([ 14C]O 2 production = 580 ± 61 nmol/min/g dry wt) of perfusion. In the adriamycin treated group, mean CO 2 production was significantly reduced at 10 min (329 ± 44 nmol/min/g dry wt, P < 0.01 v control). At 30 min, [ 14C]O 2 production in the treated group was not significantly different than controls (521 ± 65 nmol/min/g dry wt v 617 ± 36 nmol/min/g dry wt, P = N.S.). The incorporation of [ 14C]palmitate into the neutral lipid pool measured in the early subgroup was significantly reduced for adriamycin treated hearts v controls (7.2 ± 0.6 v 12.0 ± 1.4 μmol/g dry wt respectively, P < 0.01). In the control group 14C labelled neutral lipid reduced with time to 8.4 ± 1.1 μmol/g dry wt ( P < 0.05) in the late group. The adriamycin group demonstrated no significant change between early and late measurements. In conclusion, in adriamycin cardiomyopathy: (1) there is significant delay in achieving steady state palmitate oxidation, although the steady state rate is near normal; (2) palmitate incorporation into the neutral lipid pool is reduced; (3) neutral lipid pool utilization may also be reduced. These data suggest impaired uptake of palmitate into the cell in adriamycin cardiomyopathy, with a relatively maintained capacity for oxidative metabolism.