Leland C. Clark

Response of the Rabbit Lung as a Criterion of Safety for Fluorocarbon Breathing and Blood Substitutes

From the first liquid breathing experiments until now, the lung, not surprisingly, has played a central role in the evolution of fluorocarbon blood substitutes. The first breathable fluorocarbon, a mixture of F-alkylfurans(FC75), bp 102 degrees C, while a poor solvent for the lungs lining and a good solvent for oxygen and carbon dioxide, proved to cause a characteristic gas/vapor microbubble embolism following intravenous administration as an emulsion. Higher boiling fluorocarbons, e.g. F-tributylamine (FC47), bp 174 degrees C, do not produce such gas-vapor emboli. However, intermediate boiling compounds such as F-decalin (PP5), bp 141 degrees C, produce lungs which, although they certainly appear not to contain microbubble emboli, do not collapse when the thorax is opened. Such hyperinflated non-collapsible lungs (HNCL) occur in the rabbit after the intravenous infusion of F-decalin emulsions as well as after the intratracheal infusion of F-decalin neat liquid. F-decalin induced HNCL retain their appearance and low specific gravity for many weeks, gradually returning toward normal after many months. F-methyl decalin, bp 165 degrees C, does not cause HNCL after intravascular or intratracheal administration. Fluorocarbons having boiling points between 140 degrees C and 165 degrees C are being tested in order to find a perfluorinate with the highest transpiration rate, and hence vapor pressure, compatible with an acceptable body dwell time. We have given fluorocarbons intratracheally to 75, intravenously to 221 and both intratracheally and intravenously to 8 rabbits. Free radical trapping agents, antineutrophil, antiinflammatory and other drugs have been administered without appreciable decrease of HNCL. Fluorocarbon critical solution temperature, lipid solubility, emulsifiability, and other physicochemical properties may mediate the pulmonary effect. One method of preventing and treating low dose F-decalin-induced HNCL in rabbits is described.