Antithyroid drugs, thiamazole and propylthiouracil, have been widely used as therapeutic drugs in patients with hyperthyroidism. Toxicological studies have shown that the use of antithyroid drugs at an overdose causes functional and morphological changes in the thyroids in rats and dogs. 1,2) In addition, it has been reported that functional abnormalities of the thyroid gland are often accompanied by heart disease and can show unexpected responses to cardiotonics, such as digoxin.3) Therefore, to predict the effects of cardiovascular drugs, experimental animals with a very sensitive heart condition such as hypothyroidism or hyperthyroidism are required to be used. A convenient thyrotoxic model would be of great benefit for evaluating the side effects and toxicity of cardiovascular drugs.An experimental animal model with heart disease originated from abnormalities of the thyroid gland in chick embryos has been produced by the treatment with thiamazole and the pharmacological and toxicological effects of cardiotonic were examined using this model.
4)Recently, many antiarrhythmic drugs have been put on the market in Japan and classified into subcategories. Such classification of antiarrhythmic mechanisms should prove of value in predicting the therapeutic as well as toxic effects of different agents, and may be particularly important in planning combination therapy for resistant arrhythmias. Drugdrug interactions have been demonstrated for a variety of drugs, including propranolol and disopyramide, in the treatment of heart failure patients. 5,6) With the recent concern for animal rights, experimental studies using mammals have been limited in number and methods. Thus, based on social acceptance, experimental studies using chick embryos have drawn attention. In order to develop alternative methods, we have studied the biological effects of drugs on the cardiovascular system of chick embryos using physiological techniques. [7][8][9][10][11] We have evaluated the toxic interactions between propranolol and disopyramide in chick embryos. 12,13) The present study evaluated the effect of the hypothyroidism induced by thiamazole on the toxic interaction between propranolol and disopyramide in chick embryos.
MATERIALS AND METHODSFertilized eggs of White Leghorns (Omiya Poultry Laboratory, Saitama, Japan) were incubated at 37.5Ϯ0.2°C at a relative humidity of about 65%, turned automatically every hour.Thiamazole (Chugai Pharmaceutical, Tokyo, Japan), propranolol preparation (Sumitomo Pharmaceutical, Tokyo, Japan) and disopyramide preparation (Chugai Pharmaceutical, Tokyo, Japan) were used for the treatment. 1.2 mg/ 0.2 ml/egg of thiamazole was injected into the albumen of fertilized eggs on the 9th day of incubation. The control group was given 0.2 ml/egg of physiological saline in the same manner.Propranolol at 0.1 mg/egg and disopyramide at 0.3 mg/egg and were injected into the air sac of each fertilized egg on the 16th day of incubation.After the injection of propranolol and disopyramide into the thiamazole treated eggs ...