New high capacity fluorocarbon emulsions will be tested for their ability to increase brain oxygen availability. The emulsions will be administered intravenously to rabbits having implanted oxygen, hydrogen, glucose, and lactate sensors. Voltammetric currents from these sensors will be related to circulating fluorocarbon blood levels, while the animal is breathing air, oxygen, and carbon dioxide/oxygen mixtures. In addition, tissue gas and fluorocarbon vapor tensions will be measured using silicone polymeric tonometers implanted subcutaneously, intraperitoneally and on the heart. Arterial and venous blood gases, cardiac output and ECG will be monitored. PH, blood lactate and glucose will also be measured. Blood fluorocarbon levels will be measured by specific gravity, ultracentrifugation, centrifugation, combustion, and electron capture gas chromatography. Organ fluorocarbon content will be measured by combustion and by gas chromatography. Fluorocarbon emulsions are made with compounds purified and fractionated by preparative gas chromatography and with various emulsifiers including Pluronic F68, polyfluorinated amine oxides, egg lecithins, and other surfactants. Fluorocarbons will include F- decalin, F-tributylamine, and F-phenanthrene. Oncotic pressure is controlled by dextrans, hydroxyethyl starch, pentastarch, and plasma albumin. The unique ability of fluorocarbon to increase oxygen supplied to tissues in intact conscious animals is a function of the solubility of oxygen in the particular perfluorocarbon, the way in which it is dispersed in the blood, cardiac output, arterial oxygen and carbon dioxide tensions, fluorocarbon particle size, type of emulsifier used, acid-base balance, and other factors. The present proposal is to perform experiments to understand these relation- ships in terms of key physiological parameters. The role of plasma phospholipids in maintaining fluorocarbon blood levels will be studied. The synergistic effects among most of the dozen common cancer chemotherapeutic agents and fluorocarbons are based upon increased tissue oxygen tensions and oxygen transport. Understanding and control of these interrelationships is one of the primary concerns of this research. Sensing electrodes for gases and metabolites are implanted in brain, under the skin, in the liver, and intraperitoneally. Control of tissue oxygenation by fluorocarbons may be used in cardiac balloon angioplasty, cardioplegia and NMR imaging. This research should provide new means of measuring and regulating tissue oxygen tensions and tissue oxygen availability in heart attack, stroke, cancer chemotherapy, and trauma.
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