Our long-range objective is to establish optimum compositions of perfluorochemical (PFC) emulsion media for use as 02 delivery agents in vivo and in vitro. In the proposed research, we will compare the cardiac physiological and biochemical effects of APF-140E (a novel experimental emulsion composed of perfluorodecalin emulsified with nutrient free fatty acids and phospholipids), Fluosol-43 (an emulsion of perfluorotributylamine in Pluronic F-68), and physiological media (blood or a red blood cell-based perfusate). We expect APF-140E to be superior to currently-available PFC emulsions becuase: (a) its emulsifier is a biological lipid blend rather than a synthetic surfactant, (b) its PFC has a shorter biological retention time than the PFCs in current emulsion formulations, and (c) it can be formulated with high percentages of perfluorodecalin, which suggests that it will effectively deliver 02 and low Fi02. The physicochemical properties of APF-140E are also superior to those of current emulsions; notably, it is stable for long periods at room or refrigerator temperatures and has low viscosity. An isolated working rabbit heart prepartion will be used to study the cardiac effects of components of the PFC media. Physiological function, stability, and longevity of the isolated hearts will be assessed, as will the relationship between physiological function and subcellular processes including excess calcium accumulation, membrane lipid peroxidation, excess fluid accumulation, and net ATP and phosphocreatine utilization. Cardiac substructural integrity and physiological function after in vivo exposure to PFC and control media will also be determined This work will lead to the development of new synthetic 02- carrying solutions that will be useful for (a) enhancing 02 delivery to ischemic organs, (b) enhancing 02 delivery to poorly vascularized tumors to increase the efficacy of radiation therapy, (c) general transfusion use, and (d) in vitro support of organs. Such solutions will be a valuable adjunct to current fluid and blood replacement therapies and will offer new therapies for certain types of cerebrovascular and cardiac diseases and cancer.
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