THE CARDIAC EFFECTS OF BUPIVACAINE AND RO PIVACAINE ON CONTRACTILITY AND ACTION-POTENTIALS OF ISOLATED GUINEA-PIG ATRIA - INFLUENCE OF DIFFERENT EXTRACELLULAR POTASSIUM CONCENTRATIONS

Citation
H. Wulf et al., THE CARDIAC EFFECTS OF BUPIVACAINE AND RO PIVACAINE ON CONTRACTILITY AND ACTION-POTENTIALS OF ISOLATED GUINEA-PIG ATRIA - INFLUENCE OF DIFFERENT EXTRACELLULAR POTASSIUM CONCENTRATIONS, Anasthesist, 42(8), 1993, pp. 516-520
Citations number
15
Language
TEDESCO
art.tipo
Article
Categorie Soggetti
Anesthesiology
Journal title
ISSN journal
0003-2417
Volume
42
Issue
8
Year of publication
1993
Pages
516 - 520
Database
ISI
SICI code
0003-2417(1993)42:8<516:TCEOBA>2.0.ZU;2-L
Abstract
The cardiotoxicity of long acting local anaesthetics is still a matter of controversy. Therefore, the effects of bupivacaine and ropivacaine on cardiac contractility and electrophysiologic parameters were evalu ated in the presence of different extracellular potassium concentratio ns. Methods. In strips from left atria of guinea pigs action potential s were induced to obtain cumulative dose response curves for bupivacai ne (racemic mixture) and ropivacaine (S-enantiomere). Effects on force of contraction and parameters of the action potential (especially max imum upstroke velocity, dV/dt(max), as an indirect measure of fast sod ium channel function) were compared for low (2.7 mM) and high (8.7 mM) extracellular K+ concentrations (n = 7-8). Results. At low K+ concent ration, bupivacaine and ropivacaine depressed force of contraction and dV/dt(max) in a dose-dependent manner. At higher local anaesthetic co ncentrations, action potential amplitude decreased and action potentia l duration was prolonged. There was no influence on the resting membra ne potential (Tables 2, 3). At high K+ concentration, both local anaes thetics induced effects similar to those observed with low K+, but the dose-response curves for contractility and dV/dt(max) were shifted le ftward. The EC50 of bupivacaine for the negative inotropic effect and, analogously, for dV/dt(max) was approximately 10 times lower. Similar results were observed for ropivacaine (Figs. 1, 2). Conclusion. This study confirms the dependence of the cardiodepressive effects of bupiv acaine on the extracellular K+ concentration (i.e. membrane potential) . The present investigation shows a similar dependence for the effects of ropivacaine, a new long-lasting local anaesthetic. Our results con cerning the potential dependency of dV/dt(max) depression are compatib le with the binding of bupivacaine to the inactivated state of the sod ium channel protein preferentially (modulated receptor hypothesis). Th us accumulation of block will occur if stimulation frequency is in an appropriate range. Though we found striking analogies between potentia l dependency of dV/dt(max) depression and negative inotropic effect, t here is no firm evidence that the sodium channel block by bupivacaine or ropivacaine substantially participates in the latter effect. An inf luence on other ionic channels such as the calcium channel remains to be evaluated.