Milrinone

Milrinone is a PDE3 inhibitor, and also an inotrope and vasodilator. 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^[1]. 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^[4]. 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^[2]. 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^[3].