title: Phenylephrine-induced ventricular arrhythmias in dogs with inherited sudden death.
abstract: BACKGROUND
  Dogs with an inherited predisposition to sudden death display ventricular arrhythmias having certain characteristics, such as pause dependence, that are suggestive of early afterdepolarization-induced triggered activity. We hypothesized that alpha-adrenergic stimulation may facilitate the development of these arrhythmias by inducing a reflex bradycardia and by exerting a direct myocardial effect.
  
  
  RESULTS
  Twenty affected dogs and 7 unaffected dogs were studied. The incidence and severity of ventricular arrhythmias were determined after administration of phenylephrine (0.01 mg/kg IV), with or without pretreatment with propranolol (0.1 to 0.3 mg/kg IV), atropine (0.04 mg/kg IV), or prazosin (0.5 mg/kg IV). Third-degree heart block was induced by AV nodal ablation in 4 affected dogs. Phenylephrine increased ventricular arrhythmias in affected dogs, with or without pretreatment with propranolol, but did not induce ventricular arrhythmias in unaffected dogs. In dogs with intact AV nodal conduction, atropine increased sinus rate, which suppressed baseline and phenylephrine-induced arrhythmias. In dogs with heart block, arrhythmias were increased during baseline and after phenylephrine, with or without pretreatment with atropine. Prazosin and overdrive ventricular pacing suppressed phenylephrine-induced arrhythmias.
  
  
  CONCLUSIONS
  Phenylephrine increases ventricular arrhythmias in dogs with inherited sudden death via both an induction of reflex bradycardia and a direct myocardial effect. Superimposition of heightened alpha-adrenergic and vagal tone may facilitate the development of sudden death in these animals.
authors.affiliation: Department of Clinical Sciences, Cornell University, Ithaca, NY 14853-6401, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Moïse
authors.forename: P F
authors.initials: PF
authors.lastname: Moon
authors.forename: W J
authors.initials: WJ
authors.lastname: Flahive
authors.forename: D
authors.initials: D
authors.lastname: Brittain
authors.forename: H P
authors.initials: HP
authors.lastname: Pride
authors.forename: B A
authors.initials: BA
authors.lastname: Lewis
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
authors.forename: R J
authors.initials: RJ
authors.lastname: Lee
authors.forename: R F
authors.initials: RF
authors.lastname: Gilmour
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D003645:Death, Sudden; D004285:Dogs / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000187:drug effects; D008297:Male; D010375:Pedigree; D010656:Phenylephrine; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D010656:Phenylephrine; D001285:Atropine; D011433:Propranolol; D011224:Prazosin