[Characteristics of pharmacological and toxic effects of verapamil during cardiac arrhythmia in thyrotoxic and hypothyroid rats].

Aim of this study was to investigate antiarrhythmic and toxic effects of verapamil in mice and rats with thyrotoxicosis and hypothyroidism. We found that changes of thyroid status lead to the increased sensitivity of animals to toxicity of verapamil. At single intraperitoneal introduction of verapamil, LD50 was 118 +/- 7,7 mg/kg for control euthyroid mice, 53 +/- 4,1 mg/kg for hypothyroid mice, and 77 +/- 6,5 mg/kg for thyrotoxic mice. Sensitivity of rat myocardium to arrhythmogenic effects of calcium chloride increased with development of thyrotoxicosis and hypothyroidism. Effective arrhythmogenic dose of CaCl2 was 200 mg/kg for euthyroid rats and 140 mg/kg for rats with thyroid dysfunction. Intravenous introduction of verapamil had antiarrhythmic activity in rats with experimental thyroid dysfunction but at a lower effective dose. Effective preventive dose of verapamil was 3 - 4,5 mg/kg for euthyroid rats and 2 - 2,5 mg/kg for rats with thyrotoxicosis and hypothyroidism. Effective dose of verapamil during rhythm disturbance was 3 mg/kg for control euthyroid rats and 1,5 - 2 mg/kg for rats with abnormal thyroid status. These results provide a basis for the new individual approach for treatment of patients with cardiac arrhythmia combined with thyroid dysfunction.