title: The effect of cyclosporine A in hemorrhagic shock model of rats.
abstract: BACKGROUND
  The inhibition of mitochondrial permeability transition pore opening during ischemia-reperfusion can ameliorate injuries. This study aimed to investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to pressure-controlled hemorrhagic shock (mean arterial pressure, 38 ± 1 mm Hg) for 90 minutes. After the hemorrhagic shock period, rats were randomly allocated to one of three groups as follows: a control group, a CsA10 group, or a CsA50 group. CsA for the treatment groups (10 mg/kg for the CsA10 group and 50 mg/kg for the CsA50 group) or normal saline for the control group was administered via tail vein for 10 minutes, and shed blood was transfused for 15 minutes. For the survival study, animals were observed for up to 9 hours, and their survival time was recorded until death. Separate experiments were performed to examine the effect of CsA on inflammatory responses and liver injury. Rats were sacrificed at 210 minutes after the shock period, and blood and liver tissues were harvested.
  
  
  RESULTS
  Survival times were shown to be significantly longer in the CsA-treated groups (i.e., the CsA10 and CsA50 groups) than in the control group. Plasma interleukin-6 and thiobarbituric acid-reactive substances were significantly lower in the CsA50 group than in the control group and phosphorylation of Akt, GSK-3β, and Bad were significantly increased in the CsA-treated groups compared with the control group. Expressions of Bcl-2, cleaved caspase 3, and cytoplasmic cytochrome C were significantly decreased in the CsA-treated groups compared with the control group. Although histologic liver injury was not significantly different among the groups, ultrastructural changes of mitochondria were more prominent in the control group than in the CsA-treated groups.
  
  
  CONCLUSIONS
  CsA increased survival time, decreased proinflammatory cytokine and lipid peroxidation, and augmented Akt survival pathways in rats subjected to pressure-controlled hemorrhagic shock.
authors.affiliation: From the Department of Emergency Medicine (K.K., J.H.L., Y.H.J.), Seoul National University Bundang Hospital; and Department of Emergency Medicine (J.H.S.), Korean Armed Forces Capital Hospital, Gyeonggi-do; Department of Pathology (M.A.K., K.L.), Seoul National University Hospital; and Department of Emergency Medicine (Y.-S.H.), Korea University Medical Center, Seoul; and Department of Emergency Medicine (K.W.K.), Jeju National University Hospital, Jeju-do, Korea.
authors.forename: Kyuseok
authors.initials: K
authors.lastname: Kim
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: You Hwan
authors.initials: YH
authors.lastname: Jo
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Kyoungbun
authors.initials: K
authors.lastname: Lee
authors.forename: Kyeong Won
authors.initials: KW
authors.lastname: Kang
authors.forename: Yun-Sik
authors.initials: YS
authors.lastname: Hong
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D015153:Blotting, Western; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D016207:Cytokines; D016572:Cyclosporine