title: Comparison of the effects of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, refractoriness, and wavelength: an epicardial mapping study.
abstract: 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.
authors.affiliation: Laboratory of Anesthesiology and Cardiovascular Physiology, Medical School of Montpellier-Nîmes, Nîmes, France.
authors.forename: Antoine G M
authors.initials: AG
authors.lastname: Aya
authors.forename: Jean E
authors.initials: JE
authors.lastname: de la Coussaye
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Robert
authors.forename: Jacques
authors.initials: J
authors.lastname: Ripart
authors.forename: Philippe
authors.initials: P
authors.lastname: Cuvillon
authors.forename: Jean Xavier
authors.initials: JX
authors.lastname: Mazoit
authors.forename: Pascal
authors.initials: P
authors.lastname: Jeannes
authors.forename: Pascale
authors.initials: P
authors.lastname: Fabbro-Péray
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Eledjam
mesh_terms: 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
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine