[The potential dependence of the effect of bupivacaine and ropivacaine on the heart. In-vitro studies on the effect of local anesthetics on the force of contraction and the action potential in left guinea pig atria].
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 evaluated in the presence of different extracellular potassium concentrations. METHODS. In strips from left atria of guinea pigs action potentials were induced to obtain cumulative dose response curves for bupivacaine (racemic mixture) and ropivacaine (S-enantiomer). Effects on force of contraction and parameters of the action potential (especially maximum upstroke velocity, dV/dtmax, as an indirect measure of fast sodium channel function) were compared for low (2.7 mM) and high (8.7 mM) extracellular K+ concentrations (n = 7-8). RESULTS. At low K+ concentration, bupivacaine and ropivacaine depressed force of contraction and dV/dtmax in a dose-dependent manner. At higher local anaesthetic concentrations, action potential amplitude decreased and action potential duration was prolonged. There was no influence on the resting membrane potential (Tables 2, 3). At high K+ concentration, both local anaesthetics induced effects similar to those observed with low K+, but the dose-response curves for contractility and dV/dtmax were shifted leftward. The EC50 of bupivacaine for the negative inotropic effect and, analogously, for dV/dtmax 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 bupivacaine 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 concerning the potential dependency of dV/dtmax depression are compatible with the binding of bupivacaine to the inactivated state of the sodium channel protein preferentially (modulated receptor hypothesis). Thus accumulation of block will occur if stimulation frequency is in an appropriate range. Though we found striking analogies between potential dependency of dV/dtmax depression and negative inotropic effect, there is no firm evidence that the sodium channel block by bupivacaine or ropivacaine substantially participates in the latter effect. An influence on other ionic channels such as the calcium channel remains to be evaluated.
Wulf
H
H
Klinik für Anästhesiologie und Operative Intensivmedizin, Christian-Albrechts-Universität zu Kiel.
Petry
A
A
Gödicke
J
J
D000200:Action Potentials / Q000187:drug effects; D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine
Die Potentialabhängigkeit der Wirkung von Bupivacain und Ropivacain am Herzen. In vitro-Untersuchungen zur Wirkung der Lokalanästhetika auf die Kontraktionskraft und das Aktionspotential an linken Meerschweinchenatrien.