Effects of acetate on energy metabolism and function in the isolated perfused rat heart

Abstract

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.

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure

“…Bicarbonate-based hemofiltration replacement fluids have not yet been approved in Germany. Previous studies had suggested that the metabolism of acetate and lactate is impaired in critical illness and this might be able to produce acidosis [3,4]. Furthermore, it has been suggested that lactate and acetate might act as cardiovascular depressants [4].…”

“…Previous studies had suggested that the metabolism of acetate and lactate is impaired in critical illness and this might be able to produce acidosis [3,4]. Furthermore, it has been suggested that lactate and acetate might act as cardiovascular depressants [4]. The present trial was designed to assess the impact of different hemofiltration fluids on the acid-base status of patients requiring treatment with CVVH in an intensive care unit.…”

Effects of Intravascular Volume Replacement on Lung and Kidney Function and Damage in Nonseptic Experimental Lung Injury

“…32 Also, acetate can impair the fatty acid metabolism of muscle cells, reducing adenosine triphosphate and the contractile force of the myocardium, but such deleterious effects seem to occur only at relatively high plasma concentrations. 33 Colloids are able to better expand the circulatory blood volume due to their higher colloid osmotic pressure compared to crystalloids. 34,35 HES and GEL were chosen because of controversies related to immunomodulatory effects 36 and kidney damage.…”

Controversies and Issues in Hemodiafiltration Therapy

“…Among them, acetate leads to a decrease in ATP production and tissue ATP concentrations that ultimately results in impaired cardiac contractile function [18]. As this occurs at relatively low concentrations of acetate (0.1-1 mmol/l), this finding is relevant to acetate-containing dialysate used for substitution fluid in on-line hemodiafiltration.…”