Studies of pathogenesis on remnant liver dysfunction after extended hepatectomy, from the view points of changes in nitric oxide and adhesion molecule expression.

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[Purpose] This study was performed to elucidate the pathophysiology of the remnant liver dysfunction after extended hepatectomy over functional resectability of the liver, based on the relationships to nitric oxide (NO) changes and adhesion molecule expression.[Materials & Methods] Experimental adult mongorel dogs into three groups, 70%-hepatectomy (Group I), 84%-hepatectomy (Group II) and 84%-hepatectomy with simultaneous splenectomy (Group III), then serially measured following parameters until 24 hours postoperatively : 1.hepatic function test in the serum- (1) hepatocyte (GOT,GPT,AKBR), (2) endothelial cell of hepatic sinusoid (hyaluronic acid ; HA), (3) Kupffer cell (endotoxin), 2.hepatic tissue blood flow by Laser Doppler, 3.Liver tissue NO level (NO-Hb) by near-infrared spectrophotometer, and 5.ICAM-1expression in the liver tissue (immuno-histochemical staining).[Results] The hepatocyte functions were better maintained immediatly postoperatively in Group I than in Group II.HA le … More vels as endothelial function, on the other hand, were both significantly higher beginning immediatly postoperatively and negatively correlated with liver tissue blood flow. Immediately after operation, liver tissue NO levels were significantly higher in both groups, but the changes occurred at lower levels in Group II than Group I.Expression of ICAM-1 in remnant liver tissue was observed in Group II,and was particularly high in the animals with severe liver dysfunction with high HA levels and reduced NO values. In Group III,however, endothelial cell function, Kupffer cell function and liver tissue blood flow were maintained with close to levels of Group I,resulting in good remnant hepatocyte function. Therefore, NO levels and ICAM-1 expression were significantly improved by splenectomy compared with those of Group II.[Conclusion] Liver tissue NO varied depending on the sinusoidal endotherial cell function and liver tissue blood flow. The degree of ICAM-1 expression and the changes of NO levels reflected on the remnant liver dysfunction after extended hepatectomy in the early postoperative period. On the other hand, both the changes in NO levels and ICAM-1 expression were significantly improved by combined resection of spleen, suggesting that the spleen are involved in the remnant liver dysfunction in the early postoperative period, particularly in the progression of sinusoidal endothelial cell damage. Less