Hemorrhagic shock and ischemia-reperfusion (IR) injury present in military field and civilian emergency situations with several clinical and logistical challenges. Hemorrhagic shock is a leading cause of death in military combat and civilian trauma. It is the major cause of early death of injured soldiers accounting for about 50% of the deaths.
IR injury is one of the most common types of cell injuries that occur in a variety of clinical and military relevant field conditions, such as, coronary arterial disease, cardiopulmonary bypass, occlusive arterial disease, stroke, tourniquet application and re-plantation of amputated parts. In general, IR represents an acute inflammatory response after a restriction in blood supply event and subsequent restoration of blood flow.
It is well known that exposure of oxygen deprived tissues to oxygen during IR can lead to organ damage (e.g., the release of a tourniquet) because the sudden reintroduction of oxygen results in a burst of reactive oxygen/nitrogen species, that is, oxidative stress.
Oxidative stress, or an adverse biochemical event, is associated with tissues damaged produced by IR injury. Reducing oxidative stress associated with IR injury subsequent to hemorrhagic shock, tourniquet application, or other combat/civilian situations by using a clinical regimen of antioxidants, including a natural occurring body chemical, glutathione (GSH), is a reasonable science-based approach. Through early intervention with GSH or similar chemicals, we would have the potential of preventing injury morbidity and mortality.
Our objective is to determine the feasibility of using a precursor chemical for GSH in modulating the oxidative damage subsequent to IR injury. By preloading tissues with this GSH precursor chemical, we should be able to stimulate tissue to synthesize GSH which should prevent IR injury to such tissues.