Significance of oxygen free radicals in the pathophysiology of hemorrhagic shock - A protocol

Oxygen free radicals have been implicated as the deleterious agent in a variety of organ systems undergoing ischemia and subsequent reperfusion. Hemorrhagic shock represents a clinical situation that carries a high rate of morbidity and mortality despite adequate fluid resuscitation. Since this entity represents, in its most simplified sense, total body ischemia followed by reperfusion, it is likely that the generation of oxygen free radicals has some significance in the pathophysiology of this delayed morbidity. This is a research protocol, where rabbits will be subjected to severe hemorrhagic shock followed by adequate fluid resuscitation. In the first part of the experiment, free radical generation will be measured directly by Electron Paramagnetic Resonance (EPR) spectroscopy in various organ systems in rabbits before and during shock, and following resuscitation. In the second part, free radical scavengers will be introduced as an adjunct to fluid resuscitation in a group of rabbits subjected to hemorrhagic shock to see if mortality rates are affected. By acquiring a better understanding of the molecular mechanisms that may be responsible for the delayed morbidity in reperfusion injury in general, and hemorrhagic shock in particular, we will be able to better address the long-standing problem of multi system organ failure (MSOF) that often follows a successful resuscitation.