Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion.
Liver ischemia-reperfusion (I/R) injury is one of the most serious complications of hepatic surgery. In I/R, activated Kupffer cells cause platelet adhesion to sinusoidal endothelium as well as neutrophils and cause liver dysfunction. The aim of this study was to evaluate platelet dynamics in the hepatic microcirculation after I/R by intravital microscopy (IVM) and to clarify the relationship between platelet adhesion and neutrophil activation. Male Sprague-Dawley (SD) rats were divided into two groups: the control (administration of saline) group and the sivelestat group in which neutrophil activation was suppressed by sivelestat before I/R. The number of adherent platelets in sinusoid was observed up to 120 minutes after I/R by IVM. Samples of liver tissue and blood were taken for examination of histological findings, liver enzymes and inflammatory cytokines. The number of adherent platelets was significantly increased after I/R in both groups. Compared with the control group, the number of adherent platelets significantly decreased after hepatic I/R in the sivelestat group. Moreover, sivelestat improved changes of histological findings and elevation of liver enzymes. However, there was no significant difference in inflammatory cytokines of TNF-alpha, IL-1beta or IL-6. Platelet adhesion in the sinusoid is associated with liver dysfunction after I/R as well as neutrophils. Activated neutrophils induce platelet adhesion in the sinusoid of the liver.
Pak
Sugiru
S
Department of Surgery, Doctoral Program in Clinical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Kondo
Tadashi
T
Nakano
Yoritaka
Y
Murata
Soichiro
S
Fukunaga
Kiyoshi
K
Oda
Tatsuya
T
Sasaki
Ryoko
R
Ohkohchi
Nobuhiro
N
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000033:anatomy & histology / Q000473:pathology; D008102:Liver Circulation / Q000502:physiology*; D008107:Liver Diseases / Q000097:blood / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine