title: Synergistic effects of recombinant human soluble thrombomodulin and fluid-volume resuscitation in a rat lethal crush injury model.
abstract: Severe crush injury results in a high mortality rate because of acute circulatory failure and hyperkalemia. The purpose of this study was to evaluate whether administration of prophylactic-recombinant human soluble thrombomodulin (rhsTM) and/or fluid-volume resuscitation before reperfusion attenuates severe crush injury in rats. Both hindlimbs of anesthetized rats were compressed for 6 h under blocks weighing 3.5 kg each, followed by 3 h of reperfusion. In the first group, fluid resuscitation with normal saline (1 mL/kg/h) was performed throughout the experiment. In the second group, volume resuscitation treatment with normal saline (10 mL/kg/h) was initiated 60 min before the end of the crush period and was continued until the end of the experiment. In the third group, normal saline-resuscitation treatment plus rhsTM (3 mg/kg) was performed. In the fourth group, volume resuscitation treatment plus rhsTM was performed. Blood samples were collected 6 h after the end of the crush period. Complete blood count and platelets were measured. In addition, serum lactate, base deficit, serum potassium, creatine phosphokinase, blood urea nitrogen, creatinine, myoglobin, and some cytokines were evaluated. In another experiment, survival of each group was monitored for 72 h after the end of the crush period. Combined administration of rhsTM and volume resuscitation significantly decreased hemoconcentration and hyperkalemia. The serum interleukin-6 level and mortality were also significantly improved in the combination group compared with those in the other groups. We conclude that prophylactic combination of rhsTM administration and volume resuscitation may be an effective therapy for severe crush injury.
authors.affiliation: Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan. mouri@hp-emerg.med.osaka-u.ac.jp
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Mohri
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Goro
authors.initials: G
authors.lastname: Tajima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kajino
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sonoi
authors.forename: Hideo
authors.initials: H
authors.lastname: Hosotsubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogura
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kuwagata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimazu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D004195:Disease Models, Animal; D005440:Fluid Therapy / Q000379:methods*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007773:Lactates / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry*; D015427:Reperfusion Injury; D012151:Resuscitation / Q000379:methods*; D018180:Thrombomodulin / Q000097:blood*; D013997:Time Factors; D014947:Wounds and Injuries
chemical_list: D015850:Interleukin-6; D007773:Lactates; D011994:Recombinant Proteins; D018180:Thrombomodulin