• Jiaolin Ning, Liwen Mo, Hongzhi Zhao, Kaizhi Lu, Li Wang, Xinan Lai, Bob Yang, Hailin Zhao, Robert D Sanders, and Daqing Ma.
• 1Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China. 2Department of Nephrology, People's Liberation Army Chengdu Military Area Command General Hospital, Chengdu, Sichuan, China. 3Department of Hepatology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. 4State Key Laboratory of Trauma and Burns, Surgery Research Institute, Department of Traumatic Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. 5Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom. 6Surgical Outcomes Research Centre, University College London Hospital & Wellcome Department of Imaging Neuroscience, University College London, London, United Kingdom.
• Crit. Care Med. 2014 Jan 1; 42 (1): e68-78.

ObjectivesExplosive traumatic injury to an extremity may lead to both local and distant organ injury. Regional traumatic tissue hypothermia has been reported to offer systemic protection; here we investigated the protective effects of regional limb hypothermia on local tissue trauma and the lungs. Furthermore, the optimal duration of regional traumatic limb hypothermic treatment was also evaluated.DesignProspective, controlled, animal study.SettingUniversity research laboratory.SubjectsAdult male Sprague-Dawley rats.InterventionsAnesthetized rats were randomized to sham, blast limb trauma, sham and regional hypothermia for 30 minutes, and blast limb trauma and regional hypothermia for 30 minutes, 60 minutes, and 6 hours. Blast limb trauma was created using chartaceous electricity detonators.Measurements And Main ResultsDistant lung and local tissue injury following blast limb trauma were attenuated by regional traumatic limb hypothermic treatment for 30 minutes, 60 minutes, and 6 hours reflected by reduced lung histopathological changes and water content. Regional traumatic limb hypothermic treatment for 60 minutes and 6 hours failed to further attenuate distant lung and local tissue injury compared with regional traumatic limb hypothermic treatment for 30 minutes. Inhibition of cystathionine gamma-lyase/hydrogen sulfide was reduced by regional traumatic limb hypothermic treatment for 30 minutes in blast limb trauma rats. A surrogate of neutrophil accumulation, myeloperoxidase activity, and release of tumor necrosis factor-α and interleukin-6 were also attenuated by regional traumatic limb hypothermic treatment for 30 minutes in blast limb trauma rats. Oxidative stress was alleviated by regional traumatic limb hypothermic treatment for 30 minutes evidenced by reduction of hydrogen peroxide and malondialdehyde and an increase of superoxide dismutase and glutathione in blast limb trauma rats.ConclusionsOur data indicate that regional traumatic limb hypothermic treatment for 30 minutes offers both local protection for traumatic tissue and systemic protection for the lungs, which is likely associated with restoration of the cystathionine gamma-lyase/hydrogen sulfide pathway and inhibition of the inflammatory response and oxidative stress.

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