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Anesth Analg 1986; 65:1107-1111
© 1986 International Anesthesia Research Society
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Comparative Toxicity of Atracurium and Metocurine in Isolated Rat Hepatocytes

Vladimir Nigrovic, MD, James E. Klaunig, PhD, Sarah L. Smith, MA, Norman E. Schultz, BS, and Aron Wajskol, MD

Departments of Anesthesiology, Pathology, and Pharmacology, Medical College of Ohio, Toledo, Ohio.

Abstract

Primary cultures of liver cells isolated from seven rats were used to study the possible toxicity of atracurium and metocurine. The muscle relaxants were separately added to the culture medium and the cells then incubated for 4 hr. The amount of lactic dehydrogenase (LDH) that leaked into the culture medium was determined at the end of incubation. The customary assumption was made that the exudation of LDH reflects the toxic effects of the relaxants. In untreated dishes, approximately 11% of the total intracellular LDH leaked out during the incubation. The net leakage of LDH produced by the relaxants was obtained by subtracting this amount from the LDH activity determined in the media of dishes with the relaxants added. On this basis, metocurine, in concentrations of 12–850 x 10–6M, did not cause a net leak of LDH. On the other hand, atracurium, in similar molar concentrations, caused a statistically significant and concentration-dependent leak of LDH that, at its maximum, amounted to more than one half of the intracellular LDH. The results are interpreted in terms of damage to cellular membranes produced by atracurium or its metabolites. Although the exact biochemical process was not identified, we hypothesize that acrylates—produced by Hofmann elimination from atracurium—might be the likely toxic species.

Key Words: TOXICITY—atracurium, metocurine • NEUROMUSCULAR RELAXANTS—atracurium, metocurine




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 Anesth. Analg.Home page
A. Amann, J. Rieder, M. Fleischer, P. Niedermuller, G. Hoffmann, A. Amberger, C. Marth, V. Nigrovic, and F. Puhringer
The Influence of Atracurium, Cisatracurium, and Mivacurium on the Proliferation of Two Human Cell Lines In Vitro
Anesth. Analg., September 1, 2001; 93(3): 690 - 696.
[Abstract] [Full Text] [PDF]

Home page
 Hum Exp ToxicolHome page
V. Makinde and F.A. Wali
A Comparative Study of Toxicity of Four Different Muscle Relaxants in Rat Isolated Hepatocytes
Human and Experimental Toxicology, July 1, 1988; 7(4): 380 - 381.
[PDF]


Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1986 by the International Anesthesia Research Society.