1996 Fiscal Year Final Research Report Summary
Mechanisns of Post-operatire Hepatic Failure after Extended Hepatectomy
| Project/Area Number |
07671363
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
MIYAZAKI Masaru Chiba Univ.1st Dept of Surg.Lecture, 医学部, 講師 (70166156)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kougi Chiba Univ.1st Dept of Surg.Assistan, 医学部, 助手 (10282477)
SIMIZU Yoshiaki Chiba Univ.1st Dept of Surg.Instructor, 医学部, 医員
AMBIRU Satoshi Chiba Univ.1st Dept of Surg.Assistan, 医学部, 助手 (30251200)
ITO Hiroshi Chiba Univ.1st Dept of Surg.Assistan, 医学部, 助手 (00232463)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Hepatic resection / Hepatic failure / Neutrophil / Inflammatory cytokine / Obstructive jaunfice |
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| Research Abstract |
(1) The aim of this study was to assess the hypothesis that hepatic failure after extensive hepatectomy in Patients with obstructive jaundice (OJ) may be mediated by polymorphonuclear neutrophils (PMN). In the OJ group, rats underwent a partial hepatectomy of 78% after 2 weeks of cholestasis and subsequent external biliary drainage for 5 days. In the sham-operated control group, rats were partially hepatectomized 19 days after the sham surgery. The concentration of the serum cytokine-induced neutrophil chemoattractant (CINC), which is homologous with the growth-related oncogene (gro) product, a member of the human interleukin (IL) -8 family, and a major neutrophil chemtactic factor in rats, increased concomitantly with accumulation of PMNs in the hepatic sinusoids during cholestasis and subsequent external drainage. However, changes in the serum purine nucleoside phosphorylase (PNP) / alanine transaminase (ALT) ratio as a maker of sinusoidal endothelial cell (SEC) injury showed no sign
… More
ificant differences between the two groups. Intercellular adhesion molecule-1 (ICAM-1) expression on SECs was not affected by cholestasis and external drainage. After partial hepatectomy, the serum CINC concentration immediately elevated more prominently in the OJ group than in the sham-operated control group, and accumulation of PMNs in the sinusoids was more obvious and prolonged in the former. ICAM-1 expression was enhanced in both froups with a peak between 24 and 48 hours after partial hepatectomy. At this peak period, a significantly higher PNP/ALT ratio was observed in the OJ group. These results suggest that accumulation of PMNs in the sinusoidal space and ICAM-1 expression on SECs might be closely associated with the development of SEC injury after extensive hepatectomy in cholestasis.
(2) A high incidence of complications has been documented in patients with obstructive jaundice after surgical operations. Recent reports have revealed that neutrophils are involved in the mechanism of postoperative complications. However, there are few reports investigating the interaction between neutrophils and endothelial cells as an initial event in inflammatory response in obstructive jaundice. The aim of this study was to evaluate neutrophil-mediated-endothelial cell injury in patients with obstructive jaundice.
Patients were divided into three froups : those with normal liver, obstructive jaundice, relief of obstructive jaundice. Neutrophils were isolated from peripheral blood of patients individually. Human umbilical vein endothelial cells and neutrophils were co-cultured after addition of phorbol myristate acetate. The release of LDH and thrombomodulin was measured in the medium.
The release of both LDH and thrombomodulin in the group with relief of obstructive jaundice was significantly higher than in the group with normal liver (p<0.001). There was no significant difference between the group with obstructive jaundice and the group with normal liver. The elastase activity in neutrophils suspension was similarly higher in the group with relief of obstructive jaundice than in the group with normal liver (p<0.001).
This study suggests that neutrophils in patients with obstructive jaundice are not be activate before its relief. After relief of obstructive jaundice, neutrophils are strongly primed and have a potential to cause endothelial cell injury. The neutrophil "priming patients with obstructive jaundice might be associated with the frequent occurrence of postoperative complications. Less
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