Amelioration of Ischemia/Reperfusion Injury During Resuscitation from Hemorrhage by Induction of Heme Oxygenase-1 (HO-1) in a Conscious Mouse Model of Uncontrolled Hemorrhage
Final rept. 1 Sep 2009-30 Aug 2012
GENEVA FOUNDATION TACOMA WA
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Ischemia occurs whenever there is interruption of the flow of blood to tissues or organs. It is the most common cause of death in heart disease and stroke as well as traumatic injury. Survival of the initial insult is followed by further injury that occurs during the reintroduction of oxygen with the restoration of blood flow. This injury occurs following hemorrhage because some tissues are deprived of blood to protect others as part of the fight or flight response. Heme oxygenase-1 HO-1 induction is correlated with a significant reduction in ischemic injury and 1-2cyano-3, 12-dioxoleana-1, 911-dien 28-oylimidazole CDDO-lm a new synthetic triterpenoid that has been shown to possess potent anti-inflammatory and antioxidant properties, and is a potent inducer of HO-1. The hypothesis to be tested is that a significant reduction in indicies of IR injury will be obtained by induction of HO-1 during resuscitation with CDDO-IM following hemorrhage.
- Anatomy and Physiology
- Medicine and Medical Research