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

Abstract

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 lung's 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.

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

“…The stable vital signs of the canine during the experiment and the normal-looking lungs observed after the experiment implied minimal acute, unintended, bioeffects from the injected perfluoropentane droplets (36, 48, 49). However, a more thorough examination of potential bioeffects is warranted.…”

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

“…The observation that the lungs of rats, , pigs, dogs, or rabbits ,, given Fluosol or emulsions of certain PFCs, such as FX-80 or FDC, did not deflate normally at autopsy raised concerns about a possible toxic effect of PFCs in the lungs. This phenomenon was shown to relate to increased pulmonary residual volume (IPRV) due to retention of air in the alveoli. , It was found to be highly species-dependent and related to the PFC's vapor pressure and excretion rate.…”

“…When MW diminishes, vapor pressure tends to increase, which can cause pulmonary complications. 222,[1451][1452][1453][1454] Such reactions were observed with the volatile FX-80 1 in diverse but not all animal species. 1451 These observations set an upper limit (around 20 Torr) at the acceptable vapor pressure, hence a lower limit (around 460) for the PFC's MW.…”

Limited Penetration of Perfluorocarbon in Porcine Pancreas Preserved by Two-Layer Method with 19Fluorine Magnetic Resonance Spectroscopy and Headspace Gas Chromatography

“…Recently, PFC content of targeted nanoparticles has been exploited for the purposes of 19 F imaging and spectroscopy to accurately quantify fibrin content in atherosclerotic plaques (14,24). Head space gas chromatography is a well-established method for detection of PFC in biologic specimens (2,5,11). It has been employed for detection of trace amounts of PFC in blood and tissues of premature lambs during liquid ventilation experiments (30).…”