Comparative ventricular electrophysiologic effect of Racemic bupivacaine, levobupivacaine, and ropivacaine on the isolated rabbit heart

Numerous local anesthetics have an asymmetric tetrahedron carbon, which confers stereoselective differences between the isomers. The authors attempted to quantify the depressant effect of racemic bupivacaine, levobupivacaine, and ropivacaine on myocardial ventricular conduction and on myocardial con...

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Published in:Anesthesiology (Philadelphia) 2000-09, Vol.93 (3), p.784-792
Main Authors: MAZOIT, Jean Xavier, DECAUX, Anne, BOUAZIZ, Hervé, EDOUARD, Alain
Format: Article
Language:English
Subjects:
Amides - pharmacology
Anesthetics. Neuromuscular blocking agents
Animals
Biological and medical sciences
Bupivacaine - pharmacokinetics
Bupivacaine - pharmacology
Electrocardiography - drug effects
Heart - drug effects
Heart - physiology
In Vitro Techniques
Male
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Rabbits
Ropivacaine
Stereoisomerism
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creator MAZOIT, Jean Xavier
DECAUX, Anne
BOUAZIZ, Hervé
EDOUARD, Alain
description Numerous local anesthetics have an asymmetric tetrahedron carbon, which confers stereoselective differences between the isomers. The authors attempted to quantify the depressant effect of racemic bupivacaine, levobupivacaine, and ropivacaine on myocardial ventricular conduction and on myocardial contractility. The authors studied the pharmacokinetics (outflow concentration) and pharmacodynamics (QRS widening) of the three drugs infused in an isolated rabbit heart preparation. All data were fitted simultaneously with use of mixed-effect modeling, thus allowing precise statistical comparison between the three drug parameters. The rate dependence of QRS widening was fitted separately. Racemic bupivacaine, levobupivacaine, and ropivacaine induced a calculated maximum increase in QRS duration in the ratio 1:0.4:0.3. Css50, the dose which caused half the maximum increase in QRS duration at steady state, was similar for all three drugs (22 micrometer free concentration). A rate dependence of QRS widening was observed, which was in the ratio 1:0.5:0.25 for racemic bupivacaine, levobupivacaine, and ropivacaine, respectively. In the isolated rabbit heart, racemic bupivacaine, levobupivacaine, and ropivacaine induce an increase in QRS duration in the respective ratio of 1:0.4:0.3, which was rate dependent in approximately the same ratio.
doi_str_mv 10.1097/00000542-200009000-00028
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subjects Amides - pharmacology
Anesthetics. Neuromuscular blocking agents
Animals
Biological and medical sciences
Bupivacaine - pharmacokinetics
Bupivacaine - pharmacology
Electrocardiography - drug effects
Heart - drug effects
Heart - physiology
In Vitro Techniques
Male
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Rabbits
Ropivacaine
Stereoisomerism
title Comparative ventricular electrophysiologic effect of Racemic bupivacaine, levobupivacaine, and ropivacaine on the isolated rabbit heart
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