title: Comparative efficacy of antiarrhythmic agents in preventing halothane-epinephrine arrhythmias in rats.
abstract: BACKGROUND
  Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats.
  
  
  METHODS
  Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents.
  
  
  RESULTS
  In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+)-channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01).
  
  
  CONCLUSIONS
  It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.
authors.affiliation: Department of Anesthesiology, Osaka University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takada
authors.forename: K
authors.initials: K
authors.lastname: Sumikawa
authors.forename: T
authors.initials: T
authors.lastname: Kamibayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Yamatodani
authors.forename: K
authors.initials: K
authors.lastname: Kawabata
authors.forename: I
authors.initials: I
authors.lastname: Yoshiya
mesh_terms: D000638:Amiodarone / Q000627:therapeutic use; D000769:Anesthesia, Inhalation; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D004837:Epinephrine / Q000633:toxicity*; D005424:Flecainide / Q000627:therapeutic use; D006221:Halothane; D007530:Isoflurane; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031; D008012:Lidocaine; D014700:Verapamil; D007530:Isoflurane; D005424:Flecainide; D000638:Amiodarone; D006221:Halothane; D004837:Epinephrine