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Anesth Analg 2006;102:792-798
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000195341.65260.87

ANESTHETIC PHARMACOLOGY

Regulation of Intracellular Calcium by Bupivacaine Isomers in Cardiac Myocytes from Wistar Rats

Núbia G. B. Chedid, PhD, Roberto T. Sudo, MD, PhD, Marli I. S. Aguiar, Margarete M. Trachez, MD, PhD, Masako O. Masuda, PhD, and Gisele Zapata-Sudo, MD, PhD

Departamento de Farmacologia Básica e Clínica, ICB, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Serviço de Anestesiologia, Universidade Federal Fluminense, Rio de Janeiro, Brazil

Address correspondence and reprint requests to Gisele Zapata-Sudo, MD, PhD, Departamento de Farmacologia Basica e Clinica, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude, Instituto de Ciencias Biomedicas, Bloco J, Sala 14, Rio de Janeiro, Brazil, 21941-590. Address e-mail to gsudo{at}farmaco.ufrj.br.

In this study we investigated the effects of a racemic mixture of bupivacaine (RS(±)bupivacaine) and its isomers (S(-)bupivacaine and R(+)bupivacaine) on the Ca2+ handling by ventricular myocytes from Wistar rats. Single ventricular myocytes were enzymatically isolated and loaded with the fluorescent Ca2+ indicator fura 2-am to estimate intracellular Ca2+ concentration during contraction and relaxation cycles. S(-)bupivacaine (10 µM) significantly increased peak amplitude and the rate of increase of Ca2+ transients in 155% ± 54% (P < 0.05) and 194% ± 94% (P < 0.01) of control. However, exposure to R(+)bupivacaine had no effect on either peak amplitude or rate of increase at any concentration tested. Saponin-skinned ventricular fibers were used to investigate the effect of bupivacaine on the intracellular Ca2+ regulation by sarcoplasmic reticulum (SR) and on the Ca2+ sensitivity of contractile system. S(-), R(+), and RS(±)bupivacaine induced Ca2+ release from SR (P < 0.01). In SR-disrupted skinned ventricular cells, bupivacaine and its isomers (5 mM) increased the sensitivity of contractile system to Ca2+. S(-), RS(±), and R(+)bupivacaine significantly increased pCa50 from 5.8 ± 0.1, 5.8 ± 0.1, and 5.8 ± 0.1, to 6.1 ± 0.1 (P < 0.05), 6.0 ± 0.1 (P < 0.05), and 6.1 ± 0.1 (P < 0.05). Ca2+ release from SR through RyR2 activation could explain the increase of Ca2+ transients in cardiac cells. Increased intracellular Ca2+ in cardiac myocytes display a stereoselectivity to S(-)bupivacaine.






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 © 2006 by the International Anesthesia Research Society.