Interactions between triiodothyronine (T3) and amiodarone in the isolated perfused rabbit heart.
The influence of 5 days' triiodothyronine (T3) administration (0,1 mg/kg/day) on myocardial uptake kinetics and electrocardiographic effects of amiodarone (4,7 10(-6)M) were examined in isolated perfused rabbit hearts. Pharmacokinetic parameters were determined by plotting the coronary sinus effluent amiodarone concentration time-data. Electrocardiographic effects were measured as percentage changes in PR, QRS and QT electrocardiogram intervals measured in hearts removed from T3 pretreated rabbits. The perfusion of normal rabbit hearts with a modified Krebs Henseleit buffer containing amiodarone prolonged PR, QRS and QT intervals by 74%, 76% and 14% respectively, while in T3 pretreated rabbit hearts, amiodarone induced a prolongation of 84% PR, 27% QRS and 9% QT. Myocardial amiodarone accumulation normalized for heart weight represented myocardial concentrations of 260.6 +/- 20.9 micrograms/g and 235.6 +/- 11.9 micrograms/g of tissue respectively in the normal and T3 pretreated groups after a 60 min perfusion. The relationship between myocardial amiodarone concentration and electrocardiographic effects on PR and QRS were linear in both groups. The data demonstrate that the thyroïd hormone T3 did not change the kinetics of the myocardial uptake of amiodarone, but that it did change the electrocardiographic effects. Although T3 potentialized the amiodarone effect on PR, it reduced its effect on intraventricular conduction and ventricular repolarisation.
Kantelip
J P
JP
Service de Physiopathologie Respiratoire et Exploration Fonctionnelle Cérébrale--Centre Hospitalier et Universitaire, Besançon.
Akdhim
H
H
D000638:Amiodarone / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D000638:Amiodarone