Reperfusion Injury After Hemorrhage: A Collective Review

G D. Rushing, MD; L D. Britt, MD, MPH


Annals of Surgery. 2008;247(6):929-937. 

In This Article

Experimental Oxygen Transporters

Initially, hemoglobin-based oxygen carriers (HBOC) were a project of the United States Army after the Vietnam War. The impetus was for a blood substitute that could be given in forward areas until soldiers were evacuated to definitive medical care. Tetrameric hemoglobin has been the front runner but is plagued with adverse organ toxicities, such as renal, hepatic, cardiovascular, and pancreatic.[35,36] Preparations that are more contemporary have been designed by cross-linking the tetramer with either diaspirin or raffinose. Unfortunately, a recent trial involving cross-linked hemoglobin had to be closed due to increased mortality in the investigational arm.[37] Another product undergoing phase III trials is a polymerized human hemoglobin product known as PolyHeme (Northfield Laboratory).[38,39] Interim analysis has shown no toxicity or increase in mortality, however, Northfield is currently preparing for review by the Food and Drug Administration. Animal studies have demonstrated that the HBOC PolyHeme improves recovery from postshock oxygen debt and reduces acute lung injury.[40] Further animal studies using swine have established that bovine polymerized hemoglobin, HBOC-201, is superior to Dextran with regard to resuscitation and survival.[41] Oxygen carrying fluids continue to evolve and develop for the treatment of shock.

Resuscitation with trans-sodium crocetinate (TSC), a vitamin A-analog, has been used in animal models for improved oxygen delivery after hemorrhage.[42,43] Increase in oxygen delivery is due to TSC-mediated diffusivity of oxygen through plasma. TSC has also shown increases in whole body oxygen consumption. No clinical trials have been performed to date; however, infusion with TSC in animal models has shown promising results.[42,43] Although oxygen-carrying fluids will continue to be studied, it must be noted that the return of oxygen to ischemic tissue heralds the beginning of reperfusion injury.


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