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The effects of amiodarone on the electrocardiogram of the guinea‐pig are not explained by interaction with thyroid hormone metabolism alone
Author(s) -
Stäubli M.,
Studer H.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10217.x
Subject(s) - amiodarone , hormone , thyroid , guinea pig , medicine , endocrinology , metabolism , thyroid hormones , pharmacology , atrial fibrillation
1 The iodine‐containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine‐containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ). Using iopanoic acid, the question was investigated, in guinea‐pigs, whether inhibition of T 4 →T 3 conversion is by itself associated with the same changes in the electrocardiogram, i.e. QT prolongation and bradycardia, as those observed during amiodarone treatment. 2 At a dose of 4 g kg −1 , iopanoic acid induced maximal inhibition of the T 4 →T 3 conversion. Although these changes were even more pronounced than those in a control group of animals treated with 2.12 g amiodarone kg −1 , neither prolongation of the QT nor a slowing of the heart rate was observed. QT prolongation and bradycardia were induced only by amiodarone treatment but not by iopanoic acid. 3 Iopanoic acid at the high toxic dose of 12 g kg −1 induced the same degree of inhibition of T 4 → T 3 conversion as the 4 g kg −1 dose. QT prolongation and slowing of the heart rate were apparent at this dose in parallel with a loss of weight. 4 It is concluded that even a maximal inhibition of the T 4 → T 3 conversion has no effect on the ECG of guinea‐pigs. The inhibition of the T 4 → T 3 conversion alone does not explain the QT prolongation and bradycardia observed with amiodarone treatment. The amiodarone effects on the ECG may represent a combination of interactions with thyroid hormones and antiadrenergic activity.