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CRITICAL CARE AND TRAUMA

The Effects of Olprinone (a Phosphodiesterase III Inhibitor) on Hepatic Vascular Bed in a Porcine Model of Endotoxemia

Etsuro Nagata, MD^*, Yasuyuki Kakihana, MD, Kazumi Tobo, MD^*, Sumikazu Isowaki, MD^*, and Yuichi Kanmura, MD^*

*Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine; and Division of Intensive Care Medicine, Kagoshima University Hospital, Kagoshima, Japan

Address correspondence and reprint requests to Etsuro Nagata, Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by endotoxin, result in hepatic metabolic deterioration followed by liver dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors, only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous infusion (1.7 µg · kg^-1 · h^-1) of endotoxin (lipopolysaccharide [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 µg · 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 hemodynamic 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 group. Furthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia.

Implications: Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.