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 hepatosplanchnic blood flow. We evaluated the e ffects of olprinone on systemic hemodynamics, hepatic circulation, and hepa tic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs receive d a continuous infusion (1.7 mug . kg(-1) . h(-1)) of endotoxin (lipopolysa ccharide [LPS]) via the portal vein for 240 min. Seven of these pigs receiv ed 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 controls. Continuous infusion of LPS caused significant reductions in hemod ynamic variables and a significant increase in arterial lactate. After the administration of olprinone during the LPS infusion, portal venous flow and hepatic oxygen delivery were increased and were higher than in the LPS gro up. Furthermore, olprinone prevented any further increase in arterial lacta te. We conclude that the administration of olprinone halted the disturbance s in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia.