The following are summaries of nine research studies and papers available regarding dextran-hemoglobin. Full copies of each of these may be obtained from Dextro-Sang Corporation.

• Dextran, a clinical volume blood expander, and human hemoglobin were synthesized by two different methods. The results, published in the Proceeds of the National Academy of Science (1976, 73;6:2128-2131), showed that a soluble dextran-hemoglobin complex offered important advantages over free hemoglobin: prevention of free hemoglobin in the urine (hemoglobinuria), and a longer functional lifespan.

• Another review of the dextran-hemoglobin compound — in the Canadian Journal of Biochemistry (1976, 55:398-403) — confirmed its ability to be prepared in different sizes of dextrans, in greater than 90 percent yield and without incurring a large increase in viscosity. The availability of dextran-hemoglobin of different molecular sizes renders it possible to produce an optimum size of the complex for potential use as a blood substitute.

The results of exchange transfusions in dogs, published in the Canadian Journal of Biochemistry (1978, 56:981-4), showed that the animals fared far better with the dextran-hemoglobin complex than with dextran alone. Total hemoglobin concentration was maintained at 5-6 percent over the first two days, and the dogs went on to a complete recovery in room air without the need for further transfusion with dextran-hemoglobin.

• Further research (Can. J. Biochem. 1980, 58, 732-6) demonstrated that a chemically bonded complex of dextran-hemoglobin offered enhanced stability against modification of the molecular structure by acid (denaturation) and reduced the affinity for binding to haptoglobin (an alpha globulin found in blood serum that can combine with free hemoglobin in the plasma and thereby prevent the loss of iron into the urine) compared with free hemoglobin. The enhanced stability reduced the potential risk that the molecular structure of dextran-hemoglobin might be modified in the plasma and form insoluble substances that may block the capillaries.

• A subsequent exchange transfusion in cats (Proceedings of the B.P.S., 1-3 April 1981) compared dextran-hemoglobin with hemoglobin or dextran alone. Of the nine cats transfused with dextran-hemoglobin, eight survived after the packed cell volume (hematocrit, the percent of the volume of whole blood that is composed of red blood cells) was lowered to 1 percent or less. With hemoglobin exchange, however, only one of five animals survived to a hematocrit of 1 percent. Cats transfused with dextran alone failed to survive to a hematocrit of 1 percent. Therefore, the study concluded that dextran-hemoglobin appeared to support cardiovascular function at a lower hematocrit than hemoglobin- or dextran-only solutions.

• Studies (Int. J. Radiation Oncology Biol. Phys. 1984;10:369-73) were performed to examine the potential of pumping dextran-hemoglobin through tissues (perfusion) to protect pigskin and mouse bone marrow against radiation damage. Some protection was indicated in both systems. In the pigskin a protection factor of 1.5 was observed for moist descaling of the tissue and 2.0 for the death of living tissue (necrosis). These results suggest the possibility of using blood substitutes to starve tissues of oxygen (hypoxia) for therapeutic purposes.

• Perfusion with deoxygenated dextran-hemoglobin provides an effective method for starving normal tissues of oxygen in order to protect them from the effects of radiation. In this study (Int. J. Radiation Oncology Biol. Phys. 1986;12:1303-6), the dependence of P50 (the half-saturation pressure of oxygen binding to dextran-hemoglobin) was analyzed as a function of temperature and pH. The variation of radioprotection with P50, and with the amount of collateral blood entering into the perfused region, was calculated. Rapid onset of extensive venous oxygen deprivation was observed when the canine gracilis muscle was perfused with deoxygenated dextran-hemoglobin, confirmed the effectiveness of dextran-hemoglobin in protecting tissue from the effects of radiation.

• A study (J Lab Clin Med.1988;111:189-93) investigated the effects of hemoglobin on renal tubular functions. While hemoglobin infused into rats was excreted by the kidneys; dextran-hemoglobin was not. Because dextran-hemoglobin has a larger molecular size than hemoglobin alone, it did not enter into the renal tubes and therefore did not cause the impairment that hemoglobin did.

• In a 1988 study, dextran-hemoglobin was examined (Biomat., Art. Cells, Art. Org., 1988;16(1-3):237-45), in exchange-transfused macaques. An attempt similar to the exchange transfusion of dogs (using 6 percent unmodified dextran-hemoglobin) was attempted with macaques but failed to sustain their recovery. After modification with inositol phosphate 4 (oxyIP4), the major regulator of ostrich erythrocytes, 6 percent right-shifted dextran-hemoglobin completed the exchange of a macaque down to 2 percent hematocrit. The animal was fully alert the next day under room air, but died on the third day when most of the right-shifted dextran-hemoglobin had left the circulation. Unlike dogs, the production of red blood cells (erythropoiesis) in the macaque was not fast enough to compensate for the loss of the dextran-hemoglobin. However, when the macaques were exchanged down to 4 percent hematocrit, they recovered without further transfusion, enriched oxygen, or any other form of therapeutic intervention.