title: Remote Ischemic Conditioning Prevents Lung and Liver Injury After Hemorrhagic Shock/Resuscitation: Potential Role of a Humoral Plasma Factor.
abstract: OBJECTIVE
  To evaluate the efficacy of remote ischemic conditioning (RIC) on organ protection after hemorrhagic shock/resuscitation (S/R) in a murine model.
  
  
  BACKGROUND
  Ischemia/reperfusion resulting from S/R contributes to multiple organ dysfunction in trauma patients. We hypothesized that RIC before shock (remote ischemic preconditioning), during shock (remote ischemic "PER"conditioning), or during resuscitation (remote ischemic "POST"conditioning) could confer organ protection. We also tested the effect of ischemic conditioned plasma on neutrophil migration in vivo using transgenic zebrafish models.
  
  
  METHODS
  C57Bl/6 mice were subjected to S/R with or without hindlimb RIC. Serum levels of alanine aminotransferase and tumor necrosis factor-alpha, and liver tumor necrosis factor-alpha and interleukin 1β mRNA were evaluated. In some experiments, lung protein leakage, cytokines, and myeloperoxidase activity were investigated. Plasma from mice subjected to RIC was microinjected into zebrafish, and neutrophil migration was assessed after tailfin transection or copper sulfate treatment.
  
  
  RESULTS
  In mice subjected to S/R, remote ischemic preconditioning, remote ischemic "PER"conditioning, and remote ischemic "POST"conditioning each significantly reduced serum alanine aminotransferase and liver mRNA expression of tumor necrosis factor-alpha and interleukin 1β and improved liver histology compared with control S/R mice. Lung injury and inflammation were also significantly reduced in mice treated with remote ischemic preconditioning. Zebrafish injected with plasma or dialyzed plasma (fraction >14 kDa) from ischemic conditioned mice had reduced neutrophil migration toward sites of injury compared with zebrafish injected with control plasma.
  
  
  CONCLUSIONS
  RIC protects against S/R-induced organ injury, in part, through a humoral factor(s), which alters neutrophil function. The beneficial effects of RIC, performed during the S/R phase of care, suggest a role for its application early in the posttrauma period.
authors.affiliation: *Department of Surgery, the Keenan Research Centre for Biomedical Science and the Zebrafish Centre for Advanced Drug Discovery, St. Michael's Hospital, Toronto, Ontario, Canada †Division of Cardiovascular Surgery, Hospital for Sick Children, Toronto, Ontario, Canada; and ‡Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Leung
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Caldarone
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Seetha
authors.initials: S
authors.lastname: Venkateswaran
authors.forename: Menachem
authors.initials: M
authors.lastname: Ailenberg
authors.forename: Brian
authors.initials: B
authors.lastname: Vadasz
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wen
authors.forename: Ori D
authors.initials: OD
authors.lastname: Rotstein
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000097:blood; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000097:blood; D019194:Ischemic Preconditioning; D008107:Liver Diseases / Q000097:blood* / Q000209:etiology / Q000473:pathology; D055370:Lung Injury / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D010949:Plasma / Q000276:immunology; D015427:Reperfusion Injury / Q000097:blood* / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000628:therapy*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015027:Zebrafish
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase