title: Recombinant thrombomodulin improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat LPS model.
abstract: BACKGROUND
  Abnormalities in vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of this study was to examine the effect of recombinant thrombomodulin (rTM) on leukocyte-endothelial interaction and subsequent malcirculation in endotoxemia.
  
  
  METHODS
  Wistar rats were administered with either low, medium or high dose of rTM (n=7 each) 2hours after lipopolysaccharide (LPS) infusion. Mesenteric microcirculation after the treatment was observed under the intravital microscopy. In another series (n=5 each), plasma levels of high-mobility group box 1 (HMGB1) levels were measured at 5hours after LPS infusion.
  
  
  RESULTS
  Microscopic findings revealed suppression in leukocyte adhesion, thrombus formation and endothelial damage with the treatment by rTM. However, high-dose rTM tended to increase the bleeding events. Thus, blood flow was better maintained with medium-dose rTM (P<0.05). The increase in HMGB1 level was significantly suppressed by medium and high-dose rTM (P<0.05, respectively).
  
  
  CONCLUSIONS
  rTM demonstrated a protective effect on microcirculation through the inhibition of leukocyte-endothelial interaction and suppression of HMGB1.
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. toshiiba@cf6.so-net.ne.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.forename: Koichiro
authors.initials: K
authors.lastname: Aihara
authors.forename: Shin
authors.initials: S
authors.lastname: Watanabe
authors.forename: Youichi
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takemoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.forename: Daphne
authors.initials: D
authors.lastname: Yang
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D018180:Thrombomodulin / Q000008:administration & dosage*
chemical_list: D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D018180:Thrombomodulin