title: Reversal of electrophysiologic and hemodynamic effects induced by high dose of bupivacaine by the combination of clonidine and dobutamine in anesthetized dogs.
abstract: The ability of clonidine and dobutamine to correct bupivacaine-induced cardiac electrophysiologic and hemodynamic impairment was evaluated in an experimental electrophysiologic model on closed-chest dogs. Five groups (n = 6) of pentobarbital-anesthetized dogs were given atropine (0.2 mg/kg IV). Group 1 was given a saline solution; all other dogs were given bupivacaine (4 mg/kg IV) over a 10-s period. Group 2 was given only bupivacaine. Group 3 was given clonidine (0.01 mg/kg IV) over a 1-min period. Group 4 was given a dobutamine infusion at 5 micrograms.kg-1.min-1. Group 5 was given the combination of clonidine and dobutamine. Bupivacaine induced bradycardia, prolonged atrioventricular conduction time (PR interval), atrioventricular node conduction time (AH interval), His-Purkinje conduction time (HV interval), and QRS duration. Bupivacaine decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval but enhanced AH interval, bradycardia, and hemodynamic depression induced by bupivacaine. Dobutamine infusion improved LV dP/dt max but did not modify bupivacaine-induced ventricular electrophysiologic impairment. The combination of clonidine and dobutamine corrected not only the electrophysiologic impairment induced by bupivacaine but also the hemodynamic depression. As the HV interval and the QRS duration could be correlated with ventricular conduction velocities, we conclude that (a) clonidine reversed the slowing of ventricular conduction velocities induced by bupivacaine, and (b) the combination of clonidine and dobutamine was able to correct the cardiac disturbances induced by bupivacaine in anesthetized dogs.
authors.affiliation: Laboratory of Cardiovascular Physiology, Montpellier Medical School, France.
authors.forename: J E
authors.initials: JE
authors.lastname: de La Coussaye
authors.forename: B
authors.initials: B
authors.lastname: Bassoul
authors.forename: J
authors.initials: J
authors.lastname: Brugada
authors.forename: B
authors.initials: B
authors.lastname: Albat
authors.forename: P A
authors.initials: PA
authors.lastname: Peray
authors.forename: J P
authors.initials: JP
authors.lastname: Gagnol
authors.forename: G
authors.initials: G
authors.lastname: Desch
authors.forename: J J
authors.initials: JJ
authors.lastname: Eledjam
authors.forename: A
authors.initials: A
authors.lastname: Sassine
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000037:antagonists & inhibitors* / Q000097:blood; D003000:Clonidine / Q000494:pharmacology*; D003864:Depression, Chemical; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004338:Drug Combinations; D004562:Electrocardiography / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration
chemical_list: D004338:Drug Combinations; D004280:Dobutamine; D003000:Clonidine; D002045:Bupivacaine