Project 3 Acellular Hb in the circulation has been proposed to be a major source of toxicity and poor outcome for transfusions involving either aged RBCs or HBOCs. One of the major overall objectives of this program project is to test the hypothesis that acellular Hbs contribute to these poor outcomes due to depletion of endothelium-generated NO and that acellular Hb toxicity can be reversed through compensatory mechanisms that generate bioactive NO. Project 3 in conjunction with the other projects will: i) determine the role of bioactive NO in the creation or exacerbation of acellular Hb induced toxicities; and ii) establish of the role of released or nitrite-generated bioactive NO in preventing, limiting, or ameliorating acellular Hb toxicities. Project 3 will contribute to these objectives through the following three