"The second part of the question, regarding the efficacy of oxygen carriers, is difficult to answer. From the discussion above, it is clear that real blood and artificial blood are not strictly comparable, so controlled comparisons are tricky. The Food and Drug Administration and the National Institutes of Health have held two major conferences to address how these new products should be developed. A provisional answer is that if the artificial product can reduce the use of blood, it will achieve a useful goal. But based on animal studies, many of us working in the field believe that HBOCs will perform their specialized function--delivery of oxygen to tissues--even better than blood."
Winslow suggests the following for further reading:
Hemoglobin-Based Red Cell Substitutes. Robert M. Winslow. Johns Hopkins University Press, 1992.T.M.S. Chang is the director of the Artificial Cells and Organs Research Centre and is professor of Physiology, Medicine and Biomedical Engineering at McGill University in Montreal. He offers another perspective on the question:
Blood Substitutes--A Moving Target. Robert M. Winslow in Nature Medicine, Vol. 1, No. 11, pages1212-1215; 1995.
Blood Substitutes. Robert M. Winslow in Science & Medicine, Vol. 4, No. 2, pages 54-63; 1996.
"Hemoglobin is the protein in red blood cells that is responsible for carrying oxygen from the lung to the other tissues. Therefore, the present approach for making blood substitutes is to use hemoglobin extracted from red blood cells. Raw hemoglobin extracted from red blood cells cannot be used as a blood substitute, however. Each hemoglobin molecule consists of four subunits, known as tetramers. When infused into the body, a hemoglobin molecule breaks down into potentially toxic half molecules, or dimers. There are also other problems related to hemoglobin in free solution. The challenge is to modify hemoglobin to allow it for use as blood substitutes.
"The first-generation hemoglobin blood substitutes rely on molecular modifications of hemoglobin, either by chemically cross-linking the molecules or by modifying them using recombinant DNA technology. So-called bifunctional agents can cross-link the hemoglobin molecules to one another to form polyhemoglobin. The cross-linked hemoglobin molecules are stable and do not break down. Some bifunctional agents can also cross-link each hemoglobin molecule internally to prevent its breakdown into dimers. Recombinant technology applied to the bacterium E. coli can produce altered hemoglobin molecules that do not break down into half molecules. Hemoglobin can also be cross-linked to soluble polymers to form so-called conjugated hemoglobin. All the above modifications also result in blood substitutes that have a greater ability to release oxygen to the tissues than do red blood cells.
"Unlike red blood cells, blood substitutes can be pasteurized, filtered and chemical-cleansed to make them sterile. These procedures remove microorganisms responsible for diseases such as AIDS and hepatitis. Because the substitutes do not have cell membranes with blood-group antigens, cross-matching and typing are not required before use. This saves time and facilities and allows on-the-spot transfusion. Furthermore, blood substitutes can be stored for more than one year, as compared with about one month for donor blood stored using standard methods.
"On the other hand, these first-generation blood substitutes can stay in the body's circulation only for about 20 to 30 hours (a typical red blood cell lasts about 100 days). Thus, their present role is restricted to short-term applications. For example, substitutes are being tested in humans for replacing blood lost during some cardiac, cancer, orthopedic and trauma surgeries. Another promising application is to ameliorate the effects of severe bleeding in traumatic injuries from accidents, disasters or wars.