Safe hypothermic storage of isolated livers is currently limited to less than 24 hours. Increased 02 delivery by a hemoglobin-based oxygen carrier during cooling may reduce hypoxia related endothelial cell damage and enhance organ survival. We will compare hepatic biochemical and physiological function during nonhypothermic(37¡C) perfusion of livers that have been hypothermically stored for 24 hours in the presence of current storage solutions or a red blood cell substitute made up of ultrapure polymerized bovine hemoglobin. Donor livers, obtained from normal fed rats, will be assessed for biliary excretion, 02 utilization, production of glucose, lactate, amino acid N, urea N, release of K+ and tissue injury enzymes (lactodehydrogenase, transaminases), residual hepatic glycogen, ATP content and histological changes to delineate the extent of hepatocellular injury with each solution. This will define the success of extending hypothermic preservation of livers, and presumably other organs, with an oxygen carrying solution.Awardee's statement of the potential commercial applications of the research:Oxygen delivery from an ultrapure red blood substitute could extend organ survival during hypoxia and increase the number of available organs for transplantation. The material developed would be HIV free and could serve as a blood substitute. Given the large number of organ transplants and blood transfusions, the product's commercial value is high.National Heart, Lung and Blood Institute (NHLBI)
