Adrenergaically mediated ventricular fibrillation in probucol-treated dogs: roles of alpha and beta adrenergic receptors.
A high incidence of sudden death due to ventricular fibrillation (VF) has been observed in dogs under chronic treatment with probucol, a new hypocholesterolemic agent. The present study describes the cardiac electrophysiologic properties of probucol-treated dogs and characterizes the electrophysiological response of these animals to manipulation of the autonomic nervous system. There was no significant difference in the spontaneous sinus cycle length, the QT interval, refractory period of the atrium, ventricle or A-V junction between normal and probucol-treated dogs. Epinephrine produced VF with few and sometimes no preceding premature ventricular extrasystoles. Electrical stimulation of the stellate ganglion induced VF in 16/19 dogs whereas stimulation of the right stellate ganglion induced VF in 1/19 dogs. Phenylephrine induced VF in 0/19 dogs, isoproterenol in 5/19 dogs, but phenylephrine + isoproterenol induced VF in 9/11 dogs in which isoproterenol did not produce VF. alpha (phentolamine) or beta (propranolol) blockade prevented initiation of VF by epinephrine, phenylephrine + is isoproterenol, and left stellate stimulation but alpha blockade did not prevent induction of VF by isoproterenol when isoproterenol alone produced VF. In this nonischemic model, we conclude that left stellate stimulation is a far more potent initiator of VF than right stellate stimulation and that induction of VF appears to require both alpha and beta adrenergic receptor stimulation.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003645:Death, Sudden; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010636:Phenols / Q000633:toxicity*; D010656:Phenylephrine / Q000494:pharmacology; D011341:Probucol / Q000378:metabolism / Q000633:toxicity*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013233:Stellate Ganglion / Q000502:physiology; D013312:Stress, Physiological / Q000503:physiopathology; D014630:Vagus Nerve / Q000502:physiology; D014693:Ventricular Fibrillation / Q000139:chemically induced*
D010636:Phenols; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D010656:Phenylephrine; D007545:Isoproterenol; D011341:Probucol; D004837:Epinephrine