Milrinone

Milrinone (Win 47203) is a PDE3 inhibitor that increases intracellular cyclic adenosine monophosphate resulting in improved ventricular function and vasodilation. (In Vitro) :Milrinone (1 μM) increases PKA activity in hypoxic myocytes to normoxic levels. Milrinone (50 nM) normalizes TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. Milrinone significantly reduces NE-induced vasoconstriction, attenuating both NE sensitivity and maximal tension generation. Inhibition of ATP-sensitive K+ channels or voltage-gated K+ channels do not prevent the milrinone-induced attenuation of NE responses. (In Vivo) :Milrinone (1 μg/kg/min, i.v.) significantly reduces PAP, PVR (18.96 ± 1.7%), and LAP (26.03 ± 2.3%) in congestive heart failure (CHF) rats. Milrinone (1 mg/mL, inhalation) results in a near-maximal reduction of PAP without significant effects on AP, decreases pulmonary artery pressure similarly in a larger collective of CHF rats. Milrinone inhalation selectively increases cAMP but not cGMP plasma concentrations in both groups. Repeated milrinone inhalations even reduce lung wet/dry weight ratio. Milrinone (49.5 μg) largely shifts the ESPVR upwards and significantly increases end-systolic pressure (ESP (0.08) ) and the systolic pressure-volume area (PVA (0.08) ) at a mid-range LV volume (0.08 mL/g myocardium) . Milrinone also slightly decreases LV ESP (ESV) and decreased Ea.