Effect of anti-tumor necrosis factor alpha on leukocyte adhesion in the liver after hemorrhagic shock: an intravital microscopic study in the rat.
Tumor necrosis factor (TNF) plays a well known role during the development of multiple organ failure, in part due to its role for the expression of adhesion molecules on endothelial cells, thereby contributing to inflammatory reactions. The purpose of this study was to investigate the effects of TNF on leukocyte-endothelial interactions in the liver as a key organ during the systemic inflammatory response syndrome. In Sprague-Dawley rats (n = 6/group) hemorrhagic shock was induced by reduction of the mean arterial blood pressure (MAP) to 40 mmHg for 45 min; resuscitation was initiated by retransfusion of shed blood (60%) and Ringer's lactate. At 1 and 5 h after resuscitation, intravital microscopy of the liver was performed after injection of acridine orange as marker of leukocytes in sham-control animals and in shock animals pretreated with anti-TNF monoclonal antibody (2 mg/kg b.w. TN3; Celltech, Slough, UK) or NaCl .9% 2 h prior to shock induction, respectively. At constant systemic hemodynamic conditions in all groups (e.g., normal MAP), sinusoidal diameters and sinusoidal blood flow were comparably decreased to approximately 75% of control values in all shock groups. Significant differences were observed particularly in respect to permanent adherent leukocytes with 31.8 +/- 4.7% in the shock/NaCl group and 20.7 +/- 2.6% (mean +/- S.E., p < .05) in the shock/TN3 group 5 h after resuscitation following hemorrhagic shock. Consistently higher adhesion rates were observed in the portal regions compared to pericentral regions of the liver lobules.(ABSTRACT TRUNCATED AT 250 WORDS)
Marzi
I
I
Department of Trauma Surgery, University of Saarland, Homburg/Saar, Germany.
Bauer
M
M
Secchi
A
A
Bahrami
S
S
Redi
H
H
Schlag
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008833:Microcirculation; D008853:Microscopy / Q000379:methods; D009102:Multiple Organ Failure / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha