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

Hemoglobin-based blood substitutes are being developed as oxygen-carrying a gents for the prevention of ischemic tissue damage and hypovolemic (low blo od 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 critica lly ill patients. Before the clinical potential of these substitutes can be fully realized, however, concerns remain as to the intrinsic toxicity of t he hemoglobin molecule, particularly the interference of the heme prostheti c group with the tissue oxidant/antioxidant balance. This review provides s ome insights into the complex redox chemistry of hemoglobin and places an e mphasis on how current knowledge may be exploited both to selectively enhan ce/suppress specific chemical reaction pathway(s) and to ultimately design safer hemoglobin-based therapeutics.