© 1981 Oxford University Press
research-article |
Enhancement of Cardiotoxic Effects of ß-Adrenergic Bronchodilators by Aminophylline in Experimental Animals
ADivision of Drug Biology Food and Drug Administration, Washington, DC 20204 BDepartment of Pathology, George Washington University Medical Center Washington, DC 20037
Enhancement of Cardiotoxic Effects of ß-Adrenergic Bronchodilators by Aminophylline in Experimental Animals. Joseph, X., Whitehurst, V.E., Bloom, S. and Balazs, T. (1981). Fundam. Appl. Toxicol. 1:443–447. To examine the cardiotoxic interaction between ß-adrenergic bronchodilators and theophylline, we tested the effects of isoproterenol or bitolterol alone and in combinations with aminophylline in experimental animals, both electrocardiographically and histologically. The sc LDSO values for isoproterenol in 4- to 5-month-old, 500–600 g (heavy) and 1.5- to 2-month-old, 150-200 g (small) male Sprague-Dawley rats were 0.6 mg/kg and 1300 mg/kg, respectively, and values for bitolterol were 4 mg/kg and >1800 mg/kg, respectively. Results of the electrocardiographic studies in heavy rats, using the calculated LD20 dosage of isoproterenol with or without pretreatment of aminophylline, demonstrated that both mortality and the arrhythmia-inducing effect of isoproterenol were significantly potentiated by aminophylline but only mortality was increased in small rats. Aminophylline also potentiated the electrocardiographic effects of 1/40 of the LDSO dosage of isoproterenol in heavy rats but did not enhance the effects of bitolterol at this dose level. Potentiation of the arrhythmogenic effect of isoproterenol was also observed in rabbits. The severity of the myocardial lesions produced by isoproterenol or bitolterol in heavy rats was significantly enhanced by aminophylline. The heavy rat appears to be a sensitive model for studying the interaction of these classes of drugs.