PHENYLEPHRINE-INDUCED VENTRICULAR ARRHYTHMIAS IN DOGS WITH INHERITED SUDDEN-DEATH

Introduction: Dogs with an inherited predisposition to sudden death di splay ventricular arrhythmias having certain characteristics, such as pause dependence, that are suggestive of early afterdepolarization-ind uced triggered activity. We hypothesized that cr-adrenergic stimulatio n may facilitate the development of these arrhythmias by inducing a re flex bradycardia and by exerting a direct myocardial effect. Methods a nd Results: Twenty affected dogs and 7 unaffected dogs were studied. T he incidence and severity of ventricular arrhythmias were determined a fter 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 TV). Third-degree heart block was indu ced by AV nodal ablation in 4 affected dogs. Phenylephrine increased v entricular arrhythmias in affected dogs, with or without pretreatment with propranolol, but did not induce ventricular arrhythmias in unaffe cted dogs. In dogs with intact AV nodal conduction, atropine increased sinus rate, which suppressed baseline and phenylephrine-induced arrhy thmias. In dogs with heart block, arrhythmias were increased during ba seline and after phenylephrine, with or without pretreatment with atro pine. Prazosin and overdrive ventricular pacing suppressed phenylephri ne-induced arrhythmias. Conclusion: Phenylephrine increases ventricula r arrhythmias in dogs with inherited sudden death via both an inductio n of reflex bradycardia and a direct myocardial effect. Superimpositio n of heightened cr-adrenergic and vagal tone may facilitate the develo pment of sudden death in these animals.