Cardiovascular Profile of UDCG 115 BS-Pimobendane and Reversibility of Catecholamine Subsensitivity in Severe Congestive Heart Failure Secondary to Idiopathic Dilated Cardiomyopathy

Abstract

The pyridazoline derivative UDCG 115 BS (pimobendane) is a new, noncatecholamine, nonglycoside inotropic compound with potent vasodilative properties which exerts its stimulatory myocardial effect by increasing the Ca2+ affinity of cardiac contractile proteins and thus improving Ca2+ utilization. The aim of this study was to characterize and quantify the hemodynamic profile of oral UDCG 115 BS in 25 patients suffering from idiopathic congestive cardiomyopathy (NYHA III) and compare these effects with the action of the beta 1-receptor agonist dobutamine. UDCG 115 BS 5 mg p.o. increased cardiac output, cardiac index, and stroke volume index by approximately 60%. With only minor changes in heart rate, ventricular filling pressures decreased by 40%. A decline in pulmonary and systemic vascular resistance (-50%), as well as in systolic, diastolic, and mean pulmonary artery pressures (-35%) were also observed. The effects of 5 mg UDCG 115 BS were comparable to those that occurred with the optimal dose of dobutamine, whereas 10 mg UDCG 115 BS induced significantly more pronounced hemodynamic changes. The effects of UDCG lasted for at least 12 h. No major side effects were observed. Continuous treatment with 10 mg UDCG 115 BS/day for greater than 5 days resulted in a significantly improved response in beta-adrenoceptor stimulation as well as a drop in endogenous plasma catecholamines to nearly normal values. We therefore conclude that UDCG 115 BS, with its unique receptor-independent mechanism of action, may represent a new therapeutic approach in the management of patients with congestive heart failure (CHF).