Hypothyroid-like effect of amiodarone in the ventricular myocardium of the rat

Summary Due to the similar electrophysiological effects of amiodarone and hypothyroidism in the myocardium, the induction of a local hypothyroid state has been proposed as the mechanism of action of amiodarone. To examine this hypothesis we have studied the influence of amiodarone on the distribution of ventricular isomyosins — a sensitive parameter of the thyroid state in the rat heart — and the effects of amiodarone on 3,5,3-triiodothyronine (T₃) myocardial nuclear receptor binding in vivo.Amiodarone induced a dosage-dependent redistribution of isomyosins similar to hypothyroidism, while simultaneously inducing a low T₃ syndrome at the higher dose level. In hypothyroid rats, which were pretreated with amiodarone, substitution of T₃ (2 g/100 g) led to a complete reversal of the myosin pattern not differing from control hypothyroid rats which were only given T₃; the effect of T₃ (0.5 g/100 g) was however partially inhibited by amiodarone. Nuclear receptor binding of T₃ determined in hypothyroid rats in vivo was unaffected by amiodarone.We conclude that amiodarone induces a hypothyroid-like state in the ventricular myocardium of rats by inhibiting the action of T₃ — an effect which cannot be attributed to an antagonism at the T₃ nuclear receptor level.