EFFECTS OF DOPEXAMINE ON HEMODYNAMICS AND OXYGEN-CONSUMPTION AFTER BETA-BLOCKADE IN LAMBS

Objectives: Dopexamine is a synthetic catecholamine with predominantly beta2 and dopaminergic adrenergic receptor activities. We investigate d its effects on systemic and myocardial hemodynamics and oxygen consu mption (VO2) in a newborn species and studied its predominant mechanis m of action. Design: Prospective dose-response study with each animal serving as it own control. Subjects: Eight chronically instrumented, u nanesthetized lambs, 9 to 11 days of age. Interventions: After surgica l instrumentation and recovery for 72 hrs, animals were infused with d opexamine at increasing doses (1, 10, and 100 mug/kg/min) for 5 mins e ach before and after beta1 (metoprolol) and beta1,beta2 (Propranolol) adrenergic receptor blockade. All studies were performed during normox ia. Measurements and Main Results: Heart rate (HR) increased with incr easing infusion rates of dopexamine and systemic arterial pressure and vascular resistance decreased. Cardiac index, left ventricular pressu re development, and systemic VO2 were unchanged, as was the rate x pre ssure product. Left circumflex coronary artery blood flow and myocardi al VO2 were unaltered. After beta1-blockade, dopexamine produced an in crease in HR and decreased systemic arterial pressure and vascular res istance. After beta1-adrenergic receptor blockade, no. change was note d in systemic or myocardial VO2, coronary blood flow, or rate x pressu re product. After beta1,beta2-blockade with propranolol, increasing in fusion rates of dopexamine resulted in decreases in systemic pressure and vascular resistance. Conclusions: Dopexamine produced significant cardiovascular effects mediated primarily by beta2-adrenergic receptor s, and also produced residual peripheral arterial vasodilation after c ombined beta1- and beta2-blockade. The latter finding suggests that do paminergic receptor stimulation may partly mediate dopexamine's effect s in newborn lambs.