Cardiac electrophysiologic effects of acute and chronic amiodarone administration in the isolated perfused rabbit heart: altered thyroid hormone metabolism.
The electrophysiologic changes produced by amiodarone were examined in the isolated buffer-perfused rabbit heart. Long-term amiodarone administration (20 mg/kg/day for 28 days) depressed the intrinsic sinus heart rate and prolonged the PR and QT intervals of the electrocardiogram (P less than .05 vs. control). Ventricular refractoriness and the AH interval of the His-bundle electrogram were prolonged (P less than .05 vs. control) without a prolongation of the HV or QRS intervals. The electrophysiologic actions observed with long-term amiodarone treatment were reversed by the simultaneous administration of triiodothyronine (T3). No differences were noted in the electrophysiologic parameters measured in hearts removed from control and long-term amiodarone- plus T3-treated rabbits. The perfusion of the normal rabbit hearts with a buffer solution containing 1 microgram/ml of amiodarone hydrochloride failed to mimic the electrophysiologic changes produced by long-term amiodarone administration. Only a prolongation of the AH and PR intervals occurred with acute drug administration. The long-term administration of amiodarone was accompanied by decreased plasma T3 concentrations and increased concentrations of the less active thyroxine and reverse T3 species. The present data demonstrate the reversal of the electrophysiologic effects of long-term amiodarone administration by T3 administration. The data also suggest that the electrophysiologic actions of long-term amiodarone administration may be due in part to an antagonism of the actions of thyroid hormones.
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D004562:Electrocardiography; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010477:Perfusion; D011817:Rabbits; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D013963:Thyroid Hormones; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D000638:Amiodarone; D013974:Thyroxine