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

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.