Effects of acetate on energy metabolism and function in the isolated perfused rat heart.
Impairment of cardiac contractile function is an important component of acetate associated hypotension during hemodialysis treatments. We examined the effect of acetate on cardiac energy metabolism using the isovolumic 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 micromol/g dry at 30 min, P < 0.05) as well as marked impairment of systolic function (dpdt = 863 +/- 135 vs. 1288 +/- 166 mm Hg/second at 30 min, P < 0.05). Although altering perfusate calcium concentrations (0.6, 1.2 and 2.4 mM) affected physiological responses to acetate (5 and 10 mM), the reductions in tissue ATP concentrations were similar. In isolated heart mitochondria, acetate (100 microM -10 mM) selectively impaired octanoate and palmityl carnitine supported State 3 respiration in a dose dependent fashion (P < 0.01), but did not affect respiration when succinate, pyruvate/malate or malate/glutamate was used as substrate. We suggest that high concentrations of acetate selectively impair fatty acid metabolism in heart issue. This in turn leads to decreases in ATP production and tissue ATP concentrations that ultimately result in impaired contractile function. As this occurs at relatively low concentrations of acetate, this finding may be relevant to other parenterally-administered acetate containing fluids.
Jacob
A D
AD
Webb Waring Institute for Biomedical Research and Denver VA Medical Center, Department of Medicine, University of Colorado School of Medicine, USA.
Elkins
N
N
Reiss
O K
OK
Chan
L
L
Shapiro
J I
JI
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D000085:Acetates; D002118:Calcium