Ad. Jacob et al., EFFECTS OF ACETATE ON ENERGY-METABOLISM AND FUNCTION IN THE ISOLATED-PERFUSED RAT-HEART, Kidney international, 52(3), 1997, pp. 755-760
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.