title: Blood pressure-targeted stepwise resuscitation for hemorrhagic shock in rats.
abstract: BACKGROUND
  Generation of reactive oxygen species (ROS) is an important mechanism of ischemia-reperfusion injury. Abrupt reoxygenation compared with slow reoxygenation has been known to increase ROS generation. Thus, slow and stepwise reperfusion can reduce ROS generation and subsequent ischemia-reperfusion injury. This study investigated the effect of slow reperfusion by blood pressure-targeted stepwise resuscitation (PSR) in hemorrhagic shock.
  
  
  METHODS
  Pressure-controlled hemorrhagic shock was induced in male Sprague-Dawley rats for 1 hour. Rats were then allocated to one of three groups (no-resuscitation group, n = 14; PSR group, n = 15; rapid normalization of blood pressure (RR) group, n = 15). Survival time and hemodynamic changes were recorded and compared. Blood samples and liver tissue were harvested after 6 hours of resuscitation in surviving rats.
  
  
  RESULTS
  All of the rats in the no-resuscitation group were expired before the end of the 6-hour observation period. Survival times were significantly longer in the PSR group than in the RR group (survival rates, 11 of 15 vs. 5 of 15, log rank p = 0.032). Plasma amino alanine transferase, histologic liver injury, and ROS generation in the liver tissue were significantly lower in the PSR group than in the RR group (all findings significant, p < 0.05). In addition, PSR significantly decreased plasma nitric oxide, liver interleukin 1β, and liver interleukin 6 compared with rapid resuscitation in addition to augmenting Akt survival pathways (all p < 0.05).
  
  
  CONCLUSIONS
  Slow reperfusion by PSR decreased mortality, ROS generation, and liver injury in rats undergoing hemorrhagic shock. Stepwise resuscitation also decreased inflammatory cytokine production and augmented Akt survival pathways.
authors.affiliation: From the Department of Emergency Medicine (J.H.L., K.K., Y.H.J., J.E.R., A.R.D., M.J.L., C.J.P., J.K., H.C.), Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do; and Department of Pathology (M.A.K, K.B.L.), Seoul National University Hospital, Seoul, Korea.
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyuseok
authors.initials: K
authors.lastname: Kim
authors.forename: You Hwan
authors.initials: YH
authors.lastname: Jo
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Kyoung-Bun
authors.initials: KB
authors.lastname: Lee
authors.forename: Joong Eui
authors.initials: JE
authors.lastname: Rhee
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Doo
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Lee
authors.forename: Chan Jong
authors.initials: CJ
authors.lastname: Park
authors.forename: Joonghee
authors.initials: J
authors.lastname: Kim
authors.forename: Heajin
authors.initials: H
authors.lastname: Chung
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis; D015424:Reperfusion / Q000379:methods; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019344:Lactic Acid; D000410:Alanine Transaminase