Bromocriptine treatment of digitalis-induced ventricular tachyarrhythmias: studies in a canine model.
Ventricular tachyarrhythmias associated with digitalis toxicity are believed to be due, in part, to cardiac glycoside-mediated increased central sympathetic neural activity. Because dopaminergic receptor agonists reduce sympathetic outflow, this study assessed effectiveness of the available dopaminergic agonist, bromocriptine, in slowing or terminating ouabain-induced ventricular tachycardia in anesthetized dogs. In all experiments, ouabain was administered intravenously (20 micrograms/kg body weight bolus injection, followed by 2.5 micrograms/kg per min infusion) until the onset of stable ventricular tachycardia. Of seven untreated dogs (Group 1), ouabain-induced ventricular tachyarrhythmias resulted in ventricular fibrillation in three, while in four dogs tachycardia persisted without significant change in rate until the study was terminated. Fourteen dogs (Group 2) received bromocriptine, either 30 micrograms/kg (Group 2A) or 50 micrograms/kg (Group 2B), after the onset of ventricular tachycardia. Tachycardia slowed in all 14 dogs and terminated with resumption of sinus rhythm in 8 of the 14. In all six dogs pretreated with the peripheral dopaminergic antagonist domperidone (Group 3), bromocriptine, 50 micrograms/kg, slowed ventricular tachycardia and in three of the six, tachycardia terminated. In contrast, of five dogs pretreated with haloperidol, a central and peripheral dopaminergic receptor antagonist (Group 4), bromocriptine, 50 micrograms/kg, failed to slow ventricular tachycardia in three, and two of the three developed ventricular fibrillation. In summary, the dopaminergic receptor agonist, bromocriptine, presumably acting at central dopaminergic receptor sites, consistently slowed and in most cases reversed ouabain-induced ventricular tachycardia in a canine model.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004294:Domperidone / Q000627:therapeutic use; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D008297:Male; D010042:Ouabain / Q000633:toxicity*; D011292:Premedication; D011954:Receptors, Dopamine / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy*; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000188:drug therapy
D011954:Receptors, Dopamine; D001971:Bromocriptine; D004294:Domperidone; D010042:Ouabain; D006220:Haloperidol