title: Lemakalim, a potassium channel agonist, reverses electrophysiological impairments induced by a large dose of bupivacaine in anaesthetized dogs.
abstract: We have examined the ability of lemakalim to correct bupivacaine-induced cardiac electrophysiological impairment in an experimental electrophysiological model in closed-chest dogs. Two groups (n = 6) of pentobarbitone-anaesthetized dogs were given atropine 0.2 mg kg-1 i.v., and bupivacine 4 mg kg-1 i.v. over 10 s. Group 2 received also lemakalim 0.03 mg kg-1 i.v. Bupivacaine induced bradycardia, prolonged PR and His-ventricle (HV) intervals, QRS duration, QTc and JTc intervals, decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure. Lemakalim reversed bupivacaine-induced PR, HV, QRS, QTc and JTc prolongation, and did not worsen bupivacaine-induced bradycardia and haemodynamic depression. We conclude that lemakalim can antagonize the main deleterious electrophysiological effects induced by a large dose of bupivacaine in anaesthetized dogs.
authors.affiliation: Department of Anaesthesia and Intensive Care, University Hospital of Nîmes, France.
authors.forename: J E
authors.initials: JE
authors.lastname: de La Coussaye
authors.forename: J J
authors.initials: JJ
authors.lastname: Eledjam
authors.forename: P
authors.initials: P
authors.lastname: Peray
authors.forename: P
authors.initials: P
authors.lastname: Bruelle
authors.forename: J Y
authors.initials: JY
authors.lastname: Lefrant
authors.forename: B
authors.initials: B
authors.lastname: Bassoul
authors.forename: G
authors.initials: G
authors.lastname: Desch
authors.forename: J P
authors.initials: JP
authors.lastname: Gagnol
authors.forename: A
authors.initials: A
authors.lastname: Sassine
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D002045:Bupivacaine / Q000037:antagonists & inhibitors*; D019806:Cromakalim; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D001285:Atropine; D002045:Bupivacaine