Verapamil prevents isoproterenol-induced cardiac failure in the rat

Virgin, male Sprague-Dawley rats were used to study the production of cardiac failure by a single subcutaneous injection of 85 mg/kg dl-isoproterenol (ISO) and the possible preservation of cardiac function by a pre-treatment of 50 mg/kg verapamil (VER) 5 min prior to 85 mg/kg ISO. At 24 hrs after drug injections cardiac function was assessed in anesthetized, open-chest rats by the measurement of cardiac output and by a volume loading of the heart with a 2 min, 15.3 ml/min jugular vein infusion of Tyrode's solution. Peak cardiac index and peak stroke index were depressed by ISO. VER completely prevented these signs of ISO-induced cardiac failure. A second group of rats was sacrificed 24 hrs after ISO and VER-ISO and their left ventricular calcium contents were determined. ISO caused a significant increase in left ventricular calcium content. VER attenuated the ISO-induced increase in myocardial calcium content, but did not prevent it. This data raises questions as to whether VER's property as a transarcolemmal calcium flux inhibitor was the mechanism of preservation of cardiac function following ISO administration. It is possible that VER may have preserved cardiac function by altering ISO-induced hemodynamic changes in the rat.