Ischemia is caused by a traumatic injury, whereby the interruption of blood flow to the injured area not only prevents the tissue from receiving necessary oxygen but also causes a build-up of harmful waste products that are normally removed by the blood. The longer the injured tissue is ischemic, the greater the risk of irreversible tissue damage and/or death. Unfortunately, efforts to treat the injury and surgically restore blood flow can result in a secondary injury known as reperfusion injury; this results from the sudden flood of oxygen-rich blood back into the injured tissue, which causes the built-up waste products at the injury site to be suddenly released into the blood stream. The body is unable to detoxify these waste products quickly enough, which can cause further damage to the tissue. Collectively, the damage caused by the initial injury and surgical restoration of blood flow is called ischemia reperfusion injury. It is the prevention of this type of injury that Division of Plastic Surgery Senior Scientist and Microsurgery and Regenerative Medicine Lab co-Director Aaron Dingle, PhD, will be focused on with his new two-year, $750,000 Peer Reviewed Orthopaedic Research Program Applied Research Award from the U.S. Department of Defense.
Oxygen free radicals – also called reactive oxygen species – are one of the most heavily studied waste products that can build up during ischemia.
“Because they can damage tissue DNA and prevent the capacity for the body to heal, finding ways to suppress oxygen free radicals could reduce this damage and ultimately reduce the number of amputations and deaths that result from traumatic limb injuries,” explained Dingle.
One of Dingle’s colleagues and collaborators in the McArdle Laboratory for Cancer Research, Dr. William Fahl, had previously invented a free-radical scavenger called PrC-210 that was found to protect perfused organs against ischemia reperfusion injury during transplantation. It was also found to protect healthy humans against ionizing radiation from CT scans, nuclear spills, battlefield exposures, or space travel. Dingle recognized that PrC-210 could have significant potential when applied to traumatic limb injuries, and he will be partnering with Fahl and others to test this hypothesis.
“For this project, our goal is to demonstrate that PrC-210 can rapidly stabilize limb injuries and protect severely or critically wounded limbs. We’ll do this in both small animal and clinically translatable large animal models. We’ll also be optimizing the process of producing PrC-210 in a way that is suitable for future large-scale production according to current Good Manufacturing Practice,” said Dingle. “If we’re successful and PrC-210 performs the way we think it will, this study could have significant long-term implications not only for the treatment of Active Duty Military members in combat casualty situations, but also the treatment of civilian populations with traumatic limb injuries.”