Cardiovascular effects of UD-CG 212 CL, a metabolite of pimobendan, in anaesthetized pigs

Abstract

Systemic and regional haemodynamic effects of UD-CG 212 CL (0.5-16 micrograms X kg-1 X min-1), the major metabolite of the vasodilator and cardiotonic drug pimobendan, were studied in anaesthetized pigs. The drug caused a dose-dependent decrease in left ventricular (LV) end-diastolic and arterial blood pressures while it increased systemic vascular conductance, heart rate and maxLVdP/dt. The decrease in LV end-diastolic pressure was observed at lower plasma concentrations than the increase in systemic vascular conductance. Cardiac output tended to decrease but statistical significance was achieved only with the highest concentration. These effects of UD-CG 212 CL were not altered by the blockade of beta-adrenoceptors with propranolol. The vasodilator action of UD-CG 212 CL was noticed in several organs but the effects were relatively more marked (in decreasing order of magnitude) in the adrenals, kidneys, gastrointestinal tract, brain and LV epicardium. Since both arterial pressure and cardiac output decreased, the blood flow increased significantly only in the adrenals and decreased moderately in the spleen, LV endocardium and skeletal muscles. The effects of UD-CG 212 CL on the renal and skeletal muscle haemodynamics were different from those of pimobendan, which causes vasodilatation in the skeletal muscles but not in the kidneys. The results of this study show that, like the parent compound pimobendan, UD-CG 212 CL has independent cardiotonic and vasodilator actions; the latter being more pronounced on the venous side. However, the contribution of this metabolite to the overall pharmacological activity of pimobendan appears to be limited.