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Attenuation of class 3 and sinus node effects of amiodarone by experimental hypothyroidism
M Talajic1, S Nattel, M Davies
1Department of Medicine, Montreal Heart Institute, University of Montreal, Quebec, Canada.
Insights
Amiodarone
Area of Science:
- Pharmacology
- Cardiology
- Endocrinology
Background:
- Amiodarone is a potent antiarrhythmic drug with Class III effects.
- Thyroid hormone influences cardiac function, and amiodarone's effects may involve thyroid hormone interactions.
- QT prolongation is a known side effect of amiodarone.
Purpose of the Study:
- To investigate whether intact thyroid function is necessary for amiodarone's Class III antiarrhythmic effects.
- To compare the electrocardiographic (ECG) changes induced by amiodarone in euthyroid and hypothyroid guinea pigs.
Main Methods:
- Hypothyroidism was induced in guinea pigs using radioactive iodine (I131) and methimazole.
- Euthyroid and hypothyroid guinea pigs received daily intraperitoneal injections of amiodarone (80 mg/kg) for 7 days.
- Electrocardiographic (ECG) parameters, including RR, QT, and QTc intervals, were measured and compared between groups.
Main Results:
- Induced hypothyroidism led to significant increases in body weight and baseline ECG intervals (RR, QT, QTc).
- Amiodarone treatment significantly increased RR, QT, and QTc intervals in euthyroid guinea pigs.
- In contrast, amiodarone treatment did not cause significant changes in ECG intervals in hypothyroid guinea pigs.
- Plasma amiodarone concentrations were similar in both euthyroid and hypothyroid groups.
Conclusions:
- Intact thyroid function is essential for amiodarone's Class III and sinus node effects in guinea pigs.
- These findings suggest that amiodarone's cardiac effects are, at least partly, mediated by antagonism of thyroid hormone action.
Abstract:
Amiodarone's class III effects may be due to inhibition of the cardiac effects of thyroid hormone. If so, amiodarone would not be expected to cause QT prolongation in hypothyroid subjects. The electrocardiographic (ECG) changes induced after treatment with amiodarone were compared in euthyroid and hypothyroid guinea pigs. Hypothyroidism was induced with intraperitoneal (i.p.) administration of 1 mCi I131 (eight animals). Three of these animals also received oral methimazole to block any residual thyroid hormone production. Significant increases in body weight (28 +/- 9%), RR (14 +/- 8%), QT (14 +/- 5%), and QTc (7 +/- 2%) intervals occurred after induced hypothyroidism. Pilot studies with amiodarone treatment for 4 weeks in euthyroid guinea pigs demonstrated that maximal effects on ECG intervals were achieved after 1 week of drug therapy. Therefore, both euthyroid and hypothyroid groups were treated with daily i.p. amiodarone (80 mg/kg) for 7 days. Euthyroid guinea pigs treated with amiodarone had significant increases in RR (33 +/- 10%), QT (31 +/- 15%), and corrected QT (13 +/- 11%) intervals. In contrast, when hypothyroid animals were treated with amiodarone, no statistically significant changes occurred in ECG intervals. Plasma concentrations of amiodarone did not differ between the two groups (0.7 +/- 0.6 vs. 0.7 +/- 0.4 mg/L in hypothyroid and euthyroid groups, respectively). We conclude that intact thyroid function is a prerequisite for class III and sinus node effects of amiodarone in the guinea pig. This implies that at least some of amiodarone's effects are mediated through antagonism of thyroid action.