Portable Low Volume Therapy for Severe Blood Loss

In this report we integrated the major results from our rat hemorrhagic shock model with the mechanistic details of protection from ischemia and reperfusion injury in hibernating mammals. Arousal from torpor during hibernation occurs rapidly, but there is no evidence of brain injury accompanying this extreme physiological transition. Production of the antioxidant melatonin accompanies arousal, suggesting that it plays a protective role at this time. We investigated the mechanism of melatonin receptor-mediated protection in the brain of the hibernating ground squirrel. Our portable low-volume therapy for severe blood loss is based on hibernation physiology and increases survivability of lethal hemorrhagic shock in rats. This small-volume (1ml/kg) resuscitation fluid has three main components: 4 M D-stereoisomer of beta-hydroxybutyrate (BHB), 43 mM melatonin, and 20% DMSO. Results from our rat experiments have been translated to a pig model of hemorrhagic shock. Overall these experimental findings have resulted in three patents from the U.S. Patent Office over the course of this study (Patent No.8,728,532, May 20, 2014; Patent No. 9,149,450, October 6, 2015; Patent No. 9,186,340, November 17, 2015). These findings will be presented at a Pre-IND Meeting of the FDA (PIND 130671) on July 8, 2016.