Accelerating Translation of Biostasis-Inducing Compounds into Clinical Practice Using Porcine Models

In 2006, the military improved body armor to reduce fatalities, but vulnerable areas remain. Injuries from blasts, penetrative, and blunt force can cause severe vascular, neurologic, musculoskeletal, and pulmonary injuries. The body's response to trauma triggers a survival mechanism, which can lead to long-term injury and decrease the chance of survival. Biostasis is a technique that reduces metabolic demands to preserve tissue and organ system viability. A collaborative pilot study with Wyss Institute and Vascular Perfusion Solutions demonstrated successful biostasis in an ex vivo porcine model. The goal of this project is to gain military feedback by challenging biostasis compounds in a swine model simulating traumatic extremity vascular injury, which can improve survival by limiting metabolic demand and increasing the time a wounded warfighter can get definitive treatment. We will test the hypothesis that the biostasis therapeutic, Wyss drug will afford protection against ischemia reperfusion injury at the hindlimb of swine via limiting metabolic demand to enable preservation of neuromuscular health and function. We propose translating the leading stasis drug into a porcine in vivo hind limb ischemia reperfusion model, which will be conducted concurrently with studies to develop stasis induction protocols and biomarkers. This offers the ability to truly validate the stasis induction protocols and biomarkers, since the ultimate validation of stasis efficacy is enhanced viability and lack of toxicity following tissue and organ reintegration into the host. Additionally, this task will enable validation of stasis biomarkers, which may enable their translation into eventual human use, to include predictions of the likelihood of limb reattachment or organ transplantation success.