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Effect of amiodarone on rat heart myosin isoenzymes
Abstract:
The effects of amiodarone on heart weight, production of 14C-CO2 from labelled glucose, myosin ATPase activity, and myosin isoenzyme patterns were determined by comparing control and amiodarone-treated male Wistar rats. Since it has been suggested that amiodarone may interfere with thyroid hormone action on the heart, similar experiments were also carried out in hypothyroid and amiodarone-plus-triiodothyronine(T3)-treated rats, and the data were compared to those obtained in amiodarone-treated rats. Amiodarone treatment for 6 weeks resulted in lower heart weight, decreased atrial production of 14C-CO2 from labelled glucose, decreased myosin Ca-ATPase activity, and preferential synthesis of V3 isomyosin. These effects were similar to those observed in hypothyroid rats but were lesser in magnitude. T3 treatment of amiodarone-treated rats reversed all the changes induced by amiodarone. Serum thyroxine (T4) was higher in amiodarone-treated than in control rats, while serum T3 was similar. Serum T3 was higher in the amiodarone-plus-T3 than in the amiodarone-treated group. These results show that 1) amiodarone-induced changes resemble hypothyroidism with respect to cardiac myosin expression and atrial CO2 production, 2) amiodarone causes hypothyroid-like changes despite normal serum T3 and increased serum T4, and 3) T3 reverses the effects of amiodarone. These data support the hypothesis that amiodarone inhibits the action of thyroid hormone on the heart.
Insights
Amiodarone causes heart changes similar to hypothyroidism by interfering with thyroid hormone action. Triiodothyronine (T3) treatment reversed these amiodarone-induced effects, supporting the hypothesis of thyroid hormone inhibition.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Amiodarone is an antiarrhythmic drug with known side effects.
- Thyroid hormone plays a crucial role in cardiac function.
- Previous studies suggest amiodarone may interfere with thyroid hormone action in the heart.
Purpose of the Study:
- To investigate the effects of amiodarone on cardiac parameters.
- To determine if amiodarone's cardiac effects are related to thyroid hormone action.
- To compare amiodarone-induced changes with experimentally induced hypothyroidism.
Main Methods:
- Male Wistar rats were treated with amiodarone, subjected to hypothyroidism, or treated with amiodarone plus triiodothyronine (T3).
- Measurements included heart weight, glucose metabolism (14C-CO2 production), myosin ATPase activity, and myosin isoenzyme patterns.
- Serum levels of thyroxine (T4) and T3 were analyzed.
Main Results:
- Amiodarone treatment led to decreased heart weight, reduced atrial glucose metabolism, lower myosin Ca-ATPase activity, and a shift towards V3 isomyosin synthesis.
- These amiodarone-induced changes mimicked those seen in hypothyroid rats, though to a lesser extent.
- T3 administration reversed all cardiac alterations caused by amiodarone.
- Serum T4 was elevated in amiodarone-treated rats, while T3 levels were comparable to controls, despite the observed hypothyroid-like cardiac effects.
Conclusions:
- Amiodarone induces cardiac changes resembling hypothyroidism, particularly in myosin expression and atrial metabolism.
- These effects occur despite normal serum T3 levels and elevated T4, suggesting impaired thyroid hormone action.
- The reversal of amiodarone's effects by T3 supports the hypothesis that amiodarone inhibits thyroid hormone's action on the heart.