Enhanced polymorphonuclear neutrophil-mediated endothelial cell injury and its relation to high surgical mortality rate in cirrhotic patients.
OBJECTIVE
A high incidence of complications has been documented in patients with cirrhosis after operations. Recently, polymorphonuclear neutrophils (PMN) have been revealed to have the capacity to injure vascular endothelium and to cause organ damage. Furthermore, the altered function of PMN has been shown in patients with cirrhosis. However, there are few reports investigating the interaction between PMN and endothelial cells and its relation to a high incidence of postoperative complications in cirrhosis. The aim of this study was to evaluate PMN-mediated endothelial cell injury in patients with cirrhosis.


METHODS
Patients were divided into two groups: those who had normal liver with metastatic liver carcinoma and those who had cirrhosis with hepatocellular carcinoma. All patients in both groups underwent hepatic resection. PMN were isolated from patients before operation. Human umbilical vein endothelial cells and PMN were cocultured after addition of phorbol myristate acetate. The release of lactate dehydrogenase (LDH) and thrombomodulin in the cocultured medium and the elastase activity in PMN suspension were measured.


RESULTS
The release of both LDH and thrombomodulin in the group with cirrhosis was significantly higher than in the group with normal liver. The elastase activity was similarly higher in the group with cirrhosis than in the group with normal liver. The surgical morbidity rate was remarkably higher in the group with cirrhosis (50%) than in the group with normal liver (0%).


CONCLUSIONS
This study shows that PMN have an enhanced potential to cause endothelial cell injury in patients with cirrhosis. This PMN "priming" may be responsible for the occurrence of postoperative complications in patients with cirrhosis after hepatectomy.
Shimizu
Y
Y
First Department of Surgery, School of Medicine, Chiba University, Japan.
Miyazaki
M
M
Ito
H
H
Nakagawa
K
K
Ambiru
S
S
Shimizu
H
H
Nakamura
S
S
Okuno
A
A
Nozawa
S
S
Nukui
Y
Y
Yoshitomi
H
H
Nakajim
N
N
D000328:Adult; D000368:Aged; D002273:Carcinogens / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology / Q000556:secondary; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D015994:Incidence; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008103:Liver Cirrhosis / Q000473:pathology* / Q000601:surgery; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D011183:Postoperative Complications; D015996:Survival Rate; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018180:Thrombomodulin / Q000378:metabolism
D002273:Carcinogens; D018180:Thrombomodulin; D007770:L-Lactate Dehydrogenase; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate