The Surviving Blood Loss (SBL) program is developing novel strategies to radically extend the time injured warfighters can survive critical blood loss on the battlefield before initiation of fluid and blood resuscitation. Achieving this goal will allow increased time—as much as hours or days—for evacuation, triage, and initiation of supportive therapies. An interdisciplinary effort is underway to develop comprehensive understanding of energy production, metabolism, and oxygen use and to identify and control the protective mechanisms that preserve cellular function despite critically depressed oxygen delivery. Specific investigational focus areas include mechanisms to control the metabolic state on demand, including induction of a hibernation-like state, and development of low-volume therapies that reduce tissue demand for oxygen and metabolites when full resuscitation is not available.
Significant progress has been made achieving program goals including metabolic rate reduction using hydrogen sulfide—exposure to low levels of hydrogen sulfide were shown to induce a hibernation-like state in mammals, which is highly protective against blood loss or low-oxygen environments. The treatment is believed to reduce cellular oxygen consumption by reversibly inhibiting the mitochondrial enzyme cytochrome oxidase and by acting as an electron acceptor alternative for oxygen. Resistance to effects of trauma and blood loss were also demonstrated with a single dose of the female hormone 17β estradiol. The mechanism of action is likely related to induction of widespread adaptive mechanisms at the biochemical, cellular, and physiologic levels. Other promising approaches also under investigation include novel mitochondrial targeted anti-oxidants as well as therapeutics affecting the epigenetic response to stress.
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