Pharmacology, Mechanisms of Action and Uses of Selective Phosphodiesterase Inhibitors

The Effect of Amrinone on Liver Regeneration in Experimental Hepatic Resection Model1

“…Intracellular cAMP concentration increases with adenylate cyclase enzyme activity and decreases with phosphodieasterase enzyme activity [6,7]. The effect of milrinone, a PDEI, on hepatic graft functions, as studied by Ikegami et al, is reported that cAMP levels were higher and graft functions were better in milrinone group [34].…”

“…Type 3 phosphodiesterase inhibitors (PDEIs) increase intracellular adenosine 3=,5= cyclic monophosphate (cAMP) by inhibition of phosphodiesterase enzyme, which converts cAMP to adenosine monophosphate (AMP) [6,7]. Type 3 PDEIs are used clinically for their inotropic and vasodilator effects.…”

“…Sinusoidal endothelial cells are primary targets after hepatic trauma, and cAMP plays a crucial role in these cells and their barrier functions [6,12]. These protective effects of phosfodiesterase inhibitors probably occur by inhibiting cytoplasmic Ca 2ϩ mobilization [13].…”

“…4) Anti-inflammatory effects. These effect of PDEIs occur by inhibiting the production of tumor necrosis factor [6,7,12]. 5) The inhibition of secretion of reactive oxygen species from neutrophils.…”

Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs

“…11 However, the favourable effect of milrinone on CO may be negated by increases in heart rate (HR; and subsequent increases in myocardial oxygen consumption) that sometimes accompany its administration. 12 The present study investigated the hemodynamic effects of the co-administration of landiolol and milrinone in halothane-anesthetized dogs. We hypothesized that milrinone would prevent the negative inotropic effects of landiolol but preserve the ability of landiolol to achieve optimal HR control.…”