Hibernation-Based Approaches in the Treatment of Hemorrhagic Shock

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-Leu-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.