EFFECTS OF ACETATE ON ENERGY-METABOLISM AND FUNCTION IN THE ISOLATED-PERFUSED RAT-HEART

Impairment of cardiac contractile function is an important component o f acetate associated hypotension during hemodialysis treatments. We ex amined the effect of acetate on cardiac energy metabolism using the is ovolumic isolated perfused heart model. In this preparation, acetate ( 10 M) caused decreases in tissue ATP concentrations (12.3 +/- 0.8 vs. 15.6 +/- 1.0 mu mol/g dry at 30 min, P < 0.05) as well as marked impai rment of systolic function (dpdt = 863 +/- 135 vs. 1288 +/- 166 mm Hg/ second at 30 min, P < 0.05). Although altering perfusate calcium conce ntrations (0.6, 1.2 and 2.4 mM) affected physiological responses to ac etate (5 and 10 mM), the reductions in tissue ATP concentrations were similar. In isolated heart mitochondria, acetate (100 mu M -10 mM) sel ectively impaired octanoate and palmityl carnitine supported State 3 r espiration in a dose dependent fashion (P < 0.01), but did not affect respiration when succinate, pyruvate/malate or malate-glutamate was us ed as substrate. We suggest that high concentrations of acetate select ively impair fatty acid metabolism in heart issue. This in turn leads to decreases in ATP production and tissue ATP concentrations that ulti mately result in impaired contractile function. As this occurs at rela tively low concentrations of acetate, this finding may be relevant to other parenterally-administered acetate containing fluids.