Postconditioning Effects Of Diazoxide in the Brain Following Hemorrhagic Shock and Cerebral Hypoperfusion

摘要

Hemorrhagic shock resulting from injury is the most common cause of traumatic death in both civilian and military settings. Worldwide, over 5 million people died from trauma-related injury in 2000 with up to 64% of those fatalities having suffered a coinciding brain injury. For nearly a century, researchers have investigated resuscitative strategies to better the outcomes of traumatic casualty treatments. The initial measures in management, hemostasis and volume restoration are vital but too often prove unsuccessful in improving morbidity and mortality. As a result, our team investigated the hypothesis that diazoxide (DZ), a mitochondrial KATP channel opener, could be used during resuscitation to induce a phenomenon that' in a laboratory animal model of hemorrhagic shock leading to systemic hypotension and unilateral cerebral ischemia. Male Sprague-Dawley rats underwent a 40% plasma volume hemorrhage with resuscitation one hour later. DZ was administered at one of three time points: 20 minutes before the onset of resuscitation, at the time of resuscitation, or 20 minutes after the initiation of resuscitation.