Vasoactive proterties of synthetic blood substitutes

ABSTRACT

There is a great need for the development of a safe and efficient blood substitute, to overcome the important limitations of homologous blood transfusion. Currently available cell-free hemoglobin-based oxygen-carrying solutions present oxygen transport and exchange properties similar to blood and potential benefits over conventional transfusion, including large supply, absence of transfusion reactions, no need for cross-matching, no risk for transmission of disease and long shelf life. Several experimental studies have suggested that cell-free hemoglobin is a vasoactive agent. In animal models of hemorrhagic shock, small doses of cell-free modified hemoglobin restore arterial pressure, promote adequate tissue oxygenation, and improve survival, when compared with fluids with no oxygen-carrying capacity. On the other hand, it has been demonstrated that hemoglobin-induced vasocontriction may result in decreased cardiac output, reduced blood flow to vital organs and severe pulmonary hypertension. Cell-free hemoglobin solutions cause their pressor effects by binding and scavenging nitric oxide. Although hemoglobin within the red blood cells is the natural scavenger of NO, when the hemoglobin is free in solution, NO is inactivated to a greater extend. Cell-free hemoglobins are on advanced clinical trials, despite the fact that development of a safe and efficient blood substitute depends on the availability of these products for critical evaluation by the scientific community before the widespread clinical use of these blood substitutes.