There is a great need for the development of a safe and efficient bloo
d substitute, to overcome the important limitations of homologous bloo
d transfusion. Currently available cell-free hemoglobin-based oxygen-c
arrying solutions present oxygen transport and exchange properties sim
ilar to blood and potential benefits over conventional transfusion, in
cluding large supply, absence of transfusion reactions, no need for cr
oss-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 d
oses of cell-free modified hemoglobin restore arterial pressure, promo
te adequate tissue oxygenation, and improve survival, when compared wi
th fluids with no oxygen-carrying capacity. On the other hand, it has
been demonstrated that hemoglobin-induced vasoconstriction may result
in decreased cardiac output, reduced blood flow to vital organs and se
vere pulmonary hypertension. Cell-free hemoglobin solutions cause thei
r presser effects by binding and scavenging nitric oxide. Although hem
oglobin within the red blood cells is the natural scavenger of NO, whe
n the hemoglobin is free in solution, NO is inactivated to a greater e
xtend. Cell-free hemoglobins are on advanced clinical trials, despite
the fact that several concerns raised by experimental studies have not
been adequately addressed in early clinical trials. The development o
f a safe and efficient blood substitute depends on the availability of
these products for critical evaluation by the scientific community be
fore the widespread clinical use of these blood substitutes.