Oxygen Therapeutics: Pursuit of an Alternative to the Donor Red Blood Cell (Report‪)‬

The search for blood substitutes began when our early scientific ancestors tested alternatives to human blood, including animal blood, milk, and wine. Modern research into the use of animal blood includes the work by Amberson et al, (1) who reported the successful use of a bovine hemolysate for exchange transfusions in cats and dogs. Amberson's success could not be replicated in humans, as further work revealed that human and bovine hemolysates caused renal dysfunction in human recipients. The suspected cause of this nephrotoxicity was the stromal lipid component of the red blood cell (RBC) membrane. (2,3) The Vietnam War highlighted an urgent need for an oxygen carrier that could be used on the battlefield. The obvious next step in the search for the ideal substitute was the development of stroma-free hemoglobin (Hb) (Hb tetramer). Unfortunately, in 1978 Savitsky et al (4) demonstrated renal dysfunction, hypertension, and abdominal pain using stroma-free Hb in healthy volunteers. It was hypothesized that these adverse events were due to the instability of the Hb tetramer. With the recognition of human immunodeficiency virus's potential transmission through the blood supply, private industry joined the search for an alternative oxygen carrier. Industry has focused on 2 general categories of oxygen carriers: perfluorochemicals and hemoglobin-based oxygen carriers (HBOCs). Although several of these products are undergoing clinical trials, prior attempts have resulted in adverse events in patients receiving red cell substitutes and many of these products are no longer under study.