title: Regional traumatic limb hypothermia attenuates distant hepatic and renal injury following blast limb trauma in rats.
abstract: BACKGROUND
  Blast limb injury was reported to result in distant organ injury including the lungs, which can be attenuated with transient regional hypothermia (RH) to the injured limb. We aimed to further study hepatic and renal injuries following blast limb trauma and also to evaluate the protective effects of regional traumatic limb hypothermia on such injuries in rats.
  
  
  METHODS
  Blast limb trauma (BLT) was created using chartaceous electricity detonators in anesthetized male Sprague-Dawley rats. The BLT rats were randomly allocated to undergo regional traumatic limb hypothermic treatment (RH) for 30 minutes, 60 minutes, or 6 hours immediately after the onset of blast or without RH (n = 8 per group). The severity of hepatic and renal injury was assessed through histologic examination and water content (wet/dry weight) in all animals 6 hours later. The level of plasma tumor necrosis factor α (TNF-α), interleukin 6, hydrogen sulfide (H2S), and myeloperoxidase (MPO) together with hepatic and renal MPO, malondialdehyde (MDA), superoxide dismutase, and total antioxidant capacity were measured 6 hours after the blast injury.
  
  
  RESULTS
  Following BLT, hepatic injury was evidenced by histopathologic changes, increased water content, as well as plasma alanine aminotransferase and aspartate aminotransferase. Renal histopathologic but not functional changes were also found. RH treatment for all durations attenuated this distant renal injury, but only RH treatment for 60 minutes and 6 hours attenuated distant hepatic injury following BLT. RH treatment for all durations decreased plasma TNF-α and interleukin 6, reduced liver and kidney MPO activity and kidney MDA, and elevated superoxide dismutase and total antioxidant capacity in both liver and kidneys. RH treatment for 60 minutes is the most effective duration to reduce hepatic MPO activity, plasma TNF-α, and kidney MDA.
  
  
  CONCLUSIONS
  This study indicates that BLT-induced distant renal and hepatic injury could be attenuated by RH treatment through reduction of cytokine release and inhibition of neutrophil accumulation and oxidative stress.
authors.affiliation: From the Department of Hepatology (H.Z.), Xinqiao Hospital; Department of Anesthesiology (J.N., J.D., J.G., B.Y., K.L.), Southwest Hospital; State Key Laboratory of Trauma and Burns, Surgery Research Institute, and Department of Traumatic Surgery (X.L.), Daping Hospital, Third Military Medical University, Chongqing; Department of Nephrology (L.M.), People's Liberation Army Chengdu Military Area Command General Hospital, Chengdu, Sichuan, China; and Anaesthetics, Pain Medicine and Intensive Care (L.H., D.M.), Department of Surgery and Cancer, Faculty of Medicine, London, United Kingdom.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Zhao
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Ning
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Duan
authors.forename: Jianteng
authors.initials: J
authors.lastname: Gu
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Lu
authors.forename: Liwen
authors.initials: L
authors.lastname: Mo
authors.forename: Xinan
authors.initials: X
authors.lastname: Lai
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hennah
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000150:complications / Q000628:therapy*; D006862:Hydrogen Sulfide / Q000097:blood; D007036:Hypothermia, Induced / Q000379:methods; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007869:Leg Injuries / Q000150:complications / Q000628:therapy*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009195:Peroxidase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D013482:Superoxide Dismutase; D006862:Hydrogen Sulfide