Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver.
We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.
Hisama
N
N
Department of Surgery II, Kumamoto University Medical School, Japan.
Yamaguchi
Y
Y
Okajima
K
K
Uchiba
M
M
Murakami
K
K
Mori
K
K
Yamada
S
S
Ogawa
M
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D015152:Blotting, Northern; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000097:blood; D015951:Factor Xa / Q000494:pharmacology; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000097:blood; D006133:Growth Substances / Q000096:biosynthesis* / Q000097:blood; D006493:Heparin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D000590:Amino Acid Chloromethyl Ketones; D000925:Anticoagulants; D000991:Antithrombins; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C097736:dansyl-glutamyl-glycyl-arginyl chloromethyl ketone-treated factor Xa; D000990:Antithrombin III; D006493:Heparin; D009195:Peroxidase; D015951:Factor Xa