Cardiotoxic Effects in Rats and Rabbits Treated with Terbutaline Alone and in Combination with Aminophylline

Abstract

Studies were conducted to determine the myocardial effects of a selective beta-adrenoceptor agonist, terbutaline, administered alone and in combination with aminophylline in the 4-to 5-month-old, 500-600 g (heavy) rat and the rabbit, using electrocardiographic and histopathological methods. Terbutaline given at high (5.0 mg/kg) and low (0.1 mg/kg) doses was not arrhythmogenic in the heavy rat; however, dose-dependent myocardial lesions were observed. Terbutaline given at the same doses to heavy rats pretreated with aminophylline was arrhythmogenic and produced severe cardiac lesions. Rats administered aminophylline at a dose of 18.75 mg/kg had plasma theophylline levels of 15-22 μg/ml; these concentrations are similar to the recommended human therapeutic levels, i.e., 10-20 μg/ml. The administration of terbutaline in conjunction with aminophylline did not seem to affect the plasma levels of theophylline. No arrythmias were detected in rabbits given terbutaline alone or in combination with aminophylline and no deaths occurred.

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