Abstract
The pyridazoline derivative UD-CG 115 BS (pimobendan) is a noncatecholamine, nonglycoside new inotropic compound with potent vasodilator properties that exerts stimulatory myocardial effects by increasing the Ca2+ affinity of cardiac contractile proteins, thus improving Ca2+ utilization. The aim of the present study was to characterize and quantify the hemodynamic effects of oral UD-CG 115 BS in 25 patients with idiopathic congestive cardiomyopathy (NYHA stage III) and compare these to the action of the beta 1-receptor agonist dobutamine. UD-CG 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 (-40%) and there was a decline in pulmonary and systemic vascular resistance (-50%), as well as in systolic, diastolic, and mean pulmonary artery pressure (-35%). The effects of 5 mg UD-CG 115 BS were comparable to the optimal dose of dobutamine, while 10 mg induced significantly more pronounced hemodynamic changes. The effects of UD-CG 115 BS lasted for at least 12 h. No major side effects were observed. A continuous treatment with 10 mg of UD-CG 115 BS/day over a period of 5 days resulted in a significantly improved response to beta-adrenoceptor stimulation while endogenous plasma catecholamines fell down to nearly normal values. It is concluded that UD-CG 115 BS, with its unique receptor independent mechanism of action, may represent a new therapeutic approach for management of congestive heart failure patients.
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