The goal of this project is to develop a Root effect hemoglobin-based oxygen transport material to enhance tissue oxygen delivery. Root effect hemoglobins are found in the blood of some fish. The Root effect is an exaggerated Bohr effect wherein oxygen affinity is greatly decreased at acid pH. Because of the local variation in pH it is possible to load hemoglobin in the lungs at ambient oxygen pressure, and to deliver it under vastly increased, even hyperbaric pressure, in acidic hypoxic tissues. A Root effect hemoglobin-based oxygen transport material has the potential to enhance oxygen delivery to any acidic tissue; a decreased value of pH is commonly found in hypoxic normal and malignant tissues. In Phase I techniques will be developed to permit isolation and purification of a Root effect hemoglobin from the blood of Salmo gairdneri in the quantities necessary for use in large animals and in human trials. In Phase II these techniques will be used to produce approximately 50kg of stroma free hemoglobin, which meets FDA standards for preclinical and eventual clinical testing.
This research is directed toward the development of a Root effect hemoglobin-based oxygen transport material which could be used to improve tumor oxygenation for radiation and chemotherapy. It would also have potential application in the treatment of a variety of diseases resulting from normal tissue hypoxia including myocardial infarction, cardiovascular accident, failure of tissue engraftment and wound healing, small vessel diseases, etc.