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ANESTHETIC PHARMACOLOGY

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

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.

This article has been cited by other articles:

				J.-S. David, C. Ferreti, J. Amour, B. Vivien, O. Eve, P. Petit, B. Riou, and P.-Y. Gueugniaud Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation: [Les effets de la bupivacaine, levobupivacaine et ropivacaine sur la relaxation du myocarde] Can J Anesth, March 1, 2007; 54(3): 208 - 217. [Abstract] [Full Text] [PDF]

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