The effects of olprinone (a phosphodiesterase III inhibitor) on hepatic vascular bed in a porcine model of endotoxemia

Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused b y endotoxin, result in hepatic metabolic deterioration followed by Liver dy sfunction and multiple organ failure. Among phosphodiesterase III inhibitor s, only olprinone increases hepatosplanch-nic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hep atic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs receiv ed a continuous infusion (1.7 mug.kg(-1).h(-1)) of endotoxin (lipopolysacch aride [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 mug.kg(-1).min(-1)) via a central vein from t = 150 min to t = 240 min, whereas the eight remaining pigs served as LPS control s. Continuous infusion of LPS caused significant reductions in hemodynamic variables and a significant: increase in arterial lactate. After the admini stration of olprinone during the LPS infusion, portal venous flow and hepat ic oxygen delivery were increased and were higher than in the LPS group. Fu rthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in t he hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia.