EFFECTS OF DOTARIZINE ON PERIPHERAL AND PULMONARY CIRCULATION AND CARDIAC DYNAMICS IN DOGS

The cardiovascular effects of dotarizine in 10-min intravenous infusio ns were studied in thiopental-anesthetized dogs. The effects of dotari zine 0.024 mg/kg/min almost paralleled those of saline controls; 0.079 mg/kg/min dotarizine significantly raised the stroke index and ejecti on fraction, and, at a rate of 0.25 mg/kg/min, further effects appeare d and were dose-dependent. Dotarizine produced arterial dilation in bo th systemic and pulmonary circulation: the total peripheral resistance dropped, femoral artery flow rose; aortic and pulmonary artery mean a nd diastolic pressures declined, and systolic pressures remained almos t stable. A trend of bradycardia and pulmonary artery pressure reducti on persisted for 30 min. As compared with the reduced total peripheral resistance, aortic pressure fell only moderately because of rising ca rdiac output due to a higher ejection fraction and stroke volume. Card iac preload tended to decline; contractility tended to increase. Cardi ac performance remained stable while myocardial oxygen consumption ten ded to fall, as did the pressure-rate product and the tension time ind ex. Dotarizine exerted direct cardiovascular effects similar to those of the 5-HT2-receptor antagonist ketanserin and, more generally, to ca lcium channel blockers rather than to alpha-adrenoceptor blockers.