Human Recombinant Decay-Accelerating Factor (DAF) Increases Survival and Limits Tissue Injury After Hemorrhagic Shock

摘要

The current wars in Iraq and Afghanistan have resulted in the highest rates of combat casualties experienced by the U.S. military since the Vietnam conflict, and hemorrhage has been indentified as the principal cause of death among potentially salvageable patients. Hemorrhagic blood loss or resuscitation following hemorrhage leads to complement activation, which in turn, plays a key role in the pathogenesis of subsequent shock, tissue inflammation and multiple organ failure. The current study used a porcine model of controlled hemorrhage to determine the effects of early bolus injection of a complement inhibitor, decay-accelerating factor (DAF), administered 20 minutes after the onset of hemorrhagic shock. We report that hemorrhaged animals if untreated die 100 minutes before the procedure endpoint, whereas animals treated with DAF alone or in combination with resuscitation fluids displayed increased survival when compared to controls. Administration of DAF (5 and 25micrometers/kg) reduces the volume of Hextend required 60 minutes after achieving target blood pressure by approximately 56.9 and 62%, respectively. Furthermore, DAFtreated pigs showed improvement of hemodynamic and metabolic parameters and reduced injury in several organs including the lungs and the intestine. In summary, our data demonstrate that administration of DAF within 20 minutes of hemorrhagic shock may reduce mortality and morbidity of severely injured soldiers. Furthermore, its effect in reducing or eliminating the need for resuscitation fluids should reflect in great logistical and operational improvement during far-forward medical support missions.