Hibernation-Based Approaches in the Treatment of Hemorrhagic Shock

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6 Scopus citations


Hemorrhagic shock is the leading cause of preventable death after trauma. Hibernation-based treatment approaches have been of increasing interest for various biomedical applications. Owing to apparent similarities in tissue perfusion and metabolic activity between severe blood loss and the hibernating state, hibernation-based approaches have also emerged for the treatment of hemorrhagic shock. Research has shown that hibernators are protected from shock-induced injury and inflammation. Utilizing the adaptive mechanisms that prevent injury in these animals may help alleviate the detrimental effects of hemorrhagic shock in non-hibernating species. This review describes hibernation-based preclinical and clinical approaches for the treatment of severe blood loss. Treatments include the delta opioid receptor agonist D-Ala 2-Leu 5-enkephalin (DADLE), the gasotransmitter hydrogen sulfide, combinations of adenosine, lidocaine, and magnesium (ALM) or D-beta-hydroxybutyrate and melatonin (BHB/M), and therapeutic hypothermia. While we focus on hemorrhagic shock, many of the described treatments may be used in other situations of hypoxia or ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)14-23
Number of pages10
Issue number1
StatePublished - Jul 1 2018

Bibliographical note

Funding Information:
Address reprint requests to Andrea Wolf, Division of Critical Care and Acute Care Surgery, Department of General Surgery, University of Minnesota, 420 Delaware St SE, MMC 195, Minneapolis, MN 55455. E-mail: awolf@umn.edu Part of the work described in his review was supported by USDOD ARMY, Grant W81XWH-10-2-0121. This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018 by the Shock Society.


  • Adenosine lidocaine magnesium
  • D-beta-hydroxybutyrate
  • ghrelin
  • hydrogen sulfide
  • hypothermia
  • melatonin
  • resuscitation


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