EVALUATION OF THE EFFECTS OF DOPEXAMINE, A NOVEL DA(1) RECEPTOR AND BETA(2)-ADRENOCEPTOR AGONIST, ON CARDIAC-FUNCTION AND SPLANCHNIC CIRCULATION IN A CANINE MODEL OF HEMORRHAGIC-SHOCK

In the present studies, the efficacy of dopexamine hydrochloride, a novel DA1-receptor and beta2-adrenoceptor agonist in preventing deterioration of cardiovascular function in a canine model of hemorrhagic shock was investigated. Pentobarbital-anesthetized dogs were allowed to bleed into a height-regulated reservoir and the hypotensive state (about 40 mmHg) was maintained for a period of 150 min. Subsequently, blood was reinfused and recoveries in various hemodynamic variables were monitored for an additional period of 120 min. Either aqueous solvent or dopexamine HCl was randomly selected for i.v. infusion beginning 30 min before reinfusion of the blood and until the termination of the experiment. In the solvent-treated control group, various cardiovascular variables such as cardiac output, stroke volume, celiac and superior mesenteric arterial blood flows progressively declined to 50% or less of the basal values; these changes were associated with sustained increases in the regional as well as systemic vascular resistances. Dopexamine infusion lowered vascular resistances and facilitated recoveries in various hemodynamic variables to 80% to 100% of the basal values after reinfusion of the shed blood. With the exception of a transient inotropic effect during reinfusion in the dopexamine treated group, there were no essential alterations in the myocardial contractility, during the hypotensive state and/or after reinfusion of the blood. Hence, the results indicate that the efficacy of dopexamine to reduce vascular resistance by actions at DA1-receptors and beta2-adrenoceptors would account for its ability to improve myocardial performance (secondary to reductions in afterload) and restoration of mesenteric and celiac hemodynamics. These salutary effects of dopexamine could be useful in the clinical management of hemorrhagic shock.