title: Thrombomodulin improves maternal and fetal conditions in an experimental pre-eclampsia rat model.
abstract: OBJECTIVE
  The aim of this study was to investigate whether the consecutive administration of recombinant thrombomodulin (r-TM) for 4 days improves maternal and fetal conditions and physiological outcomes in an N'-nitro-L-arginine-methyl ester hydrochloride-induced and low-dose endotoxin-induced pre-eclampsia (PE).
  
  
  METHODS
  r-TM or saline was administrated i.v. to normal pregnant and experimental PE rats for 4 days. The maternal condition, vascular endothelial growth factor receptor-1 (VEGFR-1), fetal conditions, uteroplacental blood flow (UPBF), and oxygenation in the placenta and fetal brain was evaluated on gestational day 21.
  
  
  RESULTS
  Significant increases in the mean arterial blood pressure, VEGFR-1 values and fetal death rate were observed in PE rats compared with control rats, while maternal and fetal bodyweight and fetal brain weight were substantially lower. Hypoperfusion and hypo-oxygenation in both the placenta and fetal brain tissues occurred in PE rats. Although r-TM failed to improve hypertension and affect the differences in maternal bodyweight between the groups, r-TM significantly improved hypoperfusion and fetal and maternal conditions, including VEGFR-1 values (6.5 ± 4.0 vs 2.2 ± 2.7 ng/mL, PE vs PE with r-TM, respectively; P < 0.05). Although not significant, a decrease in the fetal death rate was observed in PE rats administrated r-TM (36.1 ± 17.6% vs 25.0 ± 23.8%, P = 0.077).
  
  
  CONCLUSIONS
  The severe reductions in the UPBF and the placental oxygenation imply that regional hypoperfusion occurs in association with systemic mean arterial pressure. r-TM may be a candidate medical treatment for PE complications.
authors.affiliation: Department of Anesthesiology, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Mihwa
authors.initials: M
authors.lastname: Shin
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hino
authors.forename: Midori
authors.initials: M
authors.lastname: Tamura
authors.forename: Bunpei
authors.initials: B
authors.lastname: Ishizuka
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Nao
authors.initials: N
authors.lastname: Suzuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tateda
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000187:drug effects*; D010920:Placenta / Q000098:blood supply; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D018180:Thrombomodulin / Q000627:therapeutic use*; D014599:Uterus / Q000098:blood supply
chemical_list: D011994:Recombinant Proteins; D018180:Thrombomodulin
keywords: fetal growth restriction; pre-eclampsia; recombinant thrombomodulin; uteroplacental circulation; vascular endothelial growth factor receptor-1