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When dilazep was administered intravenously to the anesthetized donor dog, mean systemic blood pressure was dose dependently decreased. At a dose of 0.1 mg/Kg i.v., the mean blood pressure was not changed but a slight decrease in heart rate was usually observed in the donor dog. At the same time, a slight but significant decrease in atrial rate and developed tension of the isolated atrium was induced. Within a dose range of 0.3 to 1 mg/Kg i.v., dilazep caused a dose related decrease in mean blood pressure, bradycardia in the donor dog, and negative chronotropic, dromotropic and inotropic effects in the isolated atrium. At larger doses of 3 and 10 mg/Kg i.v., dilazep caused marked hypotension, frequently with severe sinus bradycardia or sinus arrest, especially in isolated atria. When dilazep was infused intraarterially at a rate of 0.2-1 micrograms/min into the cannulated sinus node artery of the isolated atrium, negative chrono- and inotropic effects were dose dependently induced. With respect to dromotropism, SA conduction time (SACT) was prolonged at infusion rates of 0.2 and 0.4 micrograms/min. But at 1 microgram, dilazep caused an increase or decrease of SACT, indicating a shift of the SA nodal pacemaker. It is concluded that dilazep has direct negative chrono-, dromo- and inotropic properties on the heart at doses which produced no significant hypotension.

Chronotropic, dromotropic and inotropic effects of dilazep in the intact dog heart and isolated atrial preparation.