title: 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]O2 production; then perfused with 1.2 nmol/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 utilization. In the control group steady state oxidation was reached in 10 min ([14C]O2 production = 580 +/- 61 nmol/min/g dry wt) of perfusion. In the adriamycin treated group, mean CO2 production was significantly reduced at 10 min (329 +/- 44 nmol/min/g dry wt, P < 0.01 v control). At 30 min, [14C]O2 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 mumol/g dry wt respectively, P < 0.01). In the control group 14C labelled neutral lipid reduced with time to 8.4 +/- 1.1 mumol/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.
authors.affiliation: Centre for Cardiovascular Research, Toronto Hospital, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: Beanlands
authors.forename: N A
authors.initials: NA
authors.lastname: Shaikh
authors.forename: W H
authors.initials: WH
authors.lastname: Wen
authors.forename: F
authors.initials: F
authors.lastname: Dawood
authors.forename: A M
authors.initials: AM
authors.lastname: Ugnat
authors.forename: P R
authors.initials: PR
authors.lastname: McLaughlin
authors.forename: R
authors.initials: R
authors.lastname: Carere
authors.forename: P P
authors.initials: PP
authors.lastname: Liu
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004317:Doxorubicin; D005227:Fatty Acids / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005227:Fatty Acids; D010168:Palmitates; D004317:Doxorubicin