Hemoglobin-based blood substitutes: oxygen carriers, pressor agents, or oxidants?

Hemoglobin-based blood substitutes are being developed as oxygen-carrying agents for the prevention of ischemic tissue damage and hypovolemic (low blood volume) shock. The ability of cell-free hemoglobin blood substitutes to affect vascular tone through the removal of nitric oxide has also prompted an evaluation of their usefulness for maintaining blood pressure in critically ill patients. Before the clinical potential of these substitutes can be fully realized, however, concerns remain as to the intrinsic toxicity of the hemoglobin molecule, particularly the interference of the heme prosthetic group with the tissue oxidant/antioxidant balance. This review provides some insights into the complex redox chemistry of hemoglobin and places an emphasis on how current knowledge may be exploited both to selectively enhance/suppress specific chemical reaction pathway(s) and to ultimately design safer hemoglobin-based therapeutics.