Comparison of the effects of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, refractoriness, and wavelength: an epicardial mapping study.
BACKGROUND
The study was designed to compare the effects of equimolar concentrations of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, anisotropy, duration and homogeneity of refractoriness, and wavelengths, and to provide a potency ratio for effects on conduction velocity.


METHODS
Isolated frozen rabbit hearts (which leave a thin layer of surviving epicardial muscle) were treated with 0.1, 1, and 10 mum racemic bupivacaine, levobupivacaine, or ropivacaine. Left ventricular longitudinal and transverse conduction velocities, anisotropic ratio, minimum pacing cycle length, use dependency, duration and dispersion of ventricular effective refractory period, and wavelengths were studied. A high-resolution mapping system was used for data acquisition. In addition to two-way analysis of variance for repeated measures, data for conduction velocities were fitted simultaneously using a nonlinear mixed-effect modeling program to allow intergroup comparison.


RESULTS
Each agent induced a concentration- and use-dependent slowing of conduction velocities, with no change of the anisotropic ratio. The use-dependent effect of levobupivacaine is similar to that of racemic bupivacaine concerning longitudinal conduction velocity. Fitting of conduction velocities provided a racemic bupivacaine to levobupivacaine and to ropivacaine ratio of 1:1.38 for concentration effect at 1,000-ms pacing cycle length, and 1:0.74 for use-dependent effect at 600-ms pacing cycle length. Racemic bupivacaine and levobupivacaine prolonged the ventricular effective refractory period, whereas ropivacaine did not. No dispersion in ventricular effective refractory period values occurred. All three agents induced significant decreases in wavelengths. This effect was not different among groups.


CONCLUSIONS
Differences among racemic bupivacaine, levobupivacaine, and ropivacaine at equimolar concentrations are mainly caused by the use-dependent effects on conduction velocities and the concentration-dependent effects on ventricular effective refractory period. Therefore, one must take into account the corresponding pacing rates when comparing the potency ratios of local anesthetics.
Aya
Antoine G M
AG
Laboratory of Anesthesiology and Cardiovascular Physiology, Medical School of Montpellier-Nîmes, Nîmes, France.
de la Coussaye
Jean E
JE
Robert
Emmanuelle
E
Ripart
Jacques
J
Cuvillon
Philippe
P
Mazoit
Jean Xavier
JX
Jeannes
Pascal
P
Fabbro-Péray
Pascale
P
Eledjam
Jean-Jacques
JJ
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016880:Anisotropy; D002045:Bupivacaine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008954:Models, Biological; D009431:Neural Conduction / Q000187:drug effects*; D010496:Pericardium / Q000187:drug effects* / Q000294:innervation; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D000077212:Ropivacaine; D013237:Stereoisomerism; D016276:Ventricular Function
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine