Comparative ventricular electrophysiologic effect of racemic bupivacaine, levobupivacaine, and ropivacaine on the isolated rabbit heart.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mazoit
J X
JX
Anesthesia Laboratory, UPRES EA392 Kremlin-Bicêtre College of Medicine, Paris-Sud University, France. jean-xavier.mazoit@kb.u-psud.fr
Decaux
A
A
Bouaziz
H
H
Edouard
A
A
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D000077212:Ropivacaine; D013237:Stereoisomerism
D000577:Amides; D000077212:Ropivacaine; D002045:Bupivacaine