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PubMed1989

[Experimental model of respiratory distress syndrome by lung lavage with fluorocarbon].

The purpose of this study was to determine how much alveolar surfactant is washed out by lung lavage with fluorocarbon and also to find out whether or not instillation of artificial surfactant can restore pulmonary function after lung lavage in rats. The lung lavage was performed manually, administering a tidal volume 5 mg (2 mg/100g body weight) of fluorocarbon for about eight seconds. This process was repeated more than 40 times. In the study group, 4 ml/kg (120 mg/kg) of artificial surfactant was instilled into the trachea, and the same amount of normal saline was instilled in the control group. The amount of phospholipids extracted in lung lavage was 16.6 +/- 3.6 mg/kg body weight in the control group and 18.9 +/- 3.7 mg/kg body weight in the experimental group. Immediately after instillation of the surfactant, arterial oxygen pressure increased from 84 +/- 17 mmHg to 195.1 +/- 26.7 mmHg, and remained high, at about 170-260 mmHg. In contrast the physiological saline treated group did not show any change. We conclude that lung lavage with fluorocarbon is an adequate ideal experimental model of respiratory distress syndrome and suggests that combination of artificial surfactant treatment after lung lavage with fluorocarbon might be a new pulmonary washing method for severe lung disease.

Animals↗
PubMed1979

[Perfluorochemical-emulsion (fluorocarbon-43) as blood gas carrier--fate of the substance after intravenous injection in rat (author's transl)].

The present paper concerns light and electron microscopic studies on cellular uptake and deposition of the oxygen and carbondioxide carrying substance "Fluorocarbon-43" after intravenous injection in rats. Phagocytosis of "Fluorocarbon-43" by blood monocytes, histiocytes, endothelial macrophages (i.e.v. Kupffersche cells) and hepatocytes as well, could be demonstrated. In our experiments cellular storage of the substance was detectable even six month after injection. In the lumina and walls of alveoli migrating macrophages with storage vacuoles were found indicating pulmonary excretion of the substance. Maximum storage of "Fluorocarbon-43" caused cellular alterations and may induce interstitial fibrosis. The question whether long term incorporation of "Fluorocarbon-43" causes irreversible alteration of organs is still a matter of conjecture because of the prolonged half-live value of storage of this substance.

Animals↗
PubMed2004

High-temperature synthesis of stable ordered mesoporous silica materials by using fluorocarbon-hydrocarbon surfactant mixtures.

Highly ordered hexagonal mesoporous silica materials (JLU-20) with uniform pore sizes have been successfully synthesized at high temperature (150-220 degrees C) by using fluorocarbon-hydrocarbon surfactant mixtures. The fluorocarbon-hydrocarbon surfactant mixtures combine the advantages of both stable fluorocarbon surfactants and ordered hydrocarbon surfactants, giving ordered and stable mixed micelles at high temperature (150-220 degrees C). Mesoporous JLU-20 shows extraordinary stability towards hydrothermal treatment (100 % steam at 800 degrees C for 2 h or boiling water for 80 h), thermal treatment (calcination at 1000 degrees C for 4 h), and toward mechanical treatment (compressed at 740 MPa). Transmission electron microscopy images of JLU-20 show well-ordered hexagonal arrays of mesopores with one-dimensional (1D) channels and further confirm that JLU-20 has a two-dimensional (2D) hexagonal (P6 mm) mesostructure. 29Si HR MAS NMR spectra of as-synthesized JLU-20 shows that JLU-20 is primarily made up of fully condensed Q4 silica units (delta=-112 ppm) with a small contribution from incompletely cross-linked Q3 (delta=-102 ppm) as deduced from the very high Q4/Q3 ratio of 6.5, indicating that the mesoporous walls of JLU-20 are fully condensed. Such unique structural features should be directly attributed to the high-temperature synthesis, which is responsible for the observed high thermal, hydrothermal, and mechanical stability of the mesoporous silica materials with well-ordered hexagonal symmetry. Furthermore, the concept of "high-temperature synthesis" is successfully extended to the preparation of three-dimensional (3D) cubic mesoporous silica materials by the assistance of a fluorocarbon surfactant as a co-template. The obtained material, designated JLU-21, has a well-ordered cubic Im3m mesostructure with fully condensed pore walls and shows unusually high hydrothermal stability, as compared with conventional cubic mesoporous silica materials such as SBA-16.

Journal Article↗
PubMed1975

Fluorocarbon aerosol propellants. VI: Interspecies differences in solubilities in blood and plasma and their possible implications in toxicity studies.

Solubilities of the three most commonly used fluorocarbon aerosol propellants were determined in the blood and plasma of humans, monkeys, dogs, rats, and mice. Differences as large as approximately fourfold in blood and more than 33-fold in plasma were found in different species. The partitioning of fluorocarbons between blood cells and plasma showed even greater differences between species. An indirect method was suggested for the calculation of plasma concentrations from total blood concentrations. A comparative evaluation was reported for the nonprotein bound fractions of fluorocarbons in the blood samples of various species. A correlation was drawn for the pharmacokinetic properties of the fluorocarbons within and between species, and a rationale was provided for the extrapolation of toxicity data from animals to humans.

Adult↗
PubMed1974

Blood fluorocarbon levels following exposure to household aerosols.

Measurement of blood fluorocarbon levels was carried out in subjects exposed to a number of household aerosol products containing fluorocarbon gases as propellants. All aerosols were used according to manufacturers' recommendations. The general purpose of the study was to determine whether with normal routine exposure to a wide variety of household aerosol products fluorocarbon could be found in the blood and if so, to check the potential toxicity of the levels reached. Daily exposure to aerosols according to the study regimen lasted four consecutive weeks; this period was preceded and followed by two weeks of abstention from exposure. At the end of each of the three periods a medical examination, including evaluation of cardiac function, respiratory function studies, and hematological and functional clinical biochemical tests was performed. All tests and assessments failed to show any indication of toxicity. No trace of fluorocarbon was found in any of the blood sampled at intervals during the study.

Adult↗
PubMed1975

The effect of fluorocarbon FC 43 on the metabolism of steroids during perfusion of the isolated rat liver.

The influence of fluorocarbon FC 43 on the metabolism of oestrogens in the isolated perfused rat liver was investigated. In comparative once-through perfusions with FC 43 emulsion or albumin solution as perfusion medium, the clearance rates of oestrone and its metabolites were determined. In perfusions with FC 43, the clearance of oestrone was lower, and the metabolites formed in the liver were more concentrated in the outflowing medium than in perfusions without fluorocarbon. This can be explained by the high affinity, even of conjugated oestrogens, to FC 43, which is established by equilibrium dialysis and partition coefficient. The results presented here show that the fluorocarbon has a strong influence of its own on the metabolism of steroids in the isolated perfused liver. Therefore, this solvent should be avoided as medium when the metabolism of steroids is studied in perfusion experiments.

Albumins↗
PubMed1975

Fluorocarbons: properties and syntheses.

The paper discusses custom syntheses of fluorocarbons for potential use as artificial blood substitutes. The term "fluorocarbon" designates a perfluorinated carbon compound which does not contain another halogen or hydrogen. Prominent requirements of an artificial blood substitute are: 1) efficient oxygen/carbon dioxide transport, 2) biological inertness, 3) low vapor pressure, 4) dispersibility to form emulsion. Fluorocarbons are superior to other liquids in dissolving oxygen and carbon dioxide. The most biologically inert halogenated alkanes are fully fluorinated. Introduction of another halogen or unsaturation decreases biological inertness. Boiling points of fluoroalkanes can be estimated from the Kinney equation. The most common method of fluorination, namely electrofluorination, is briefly described and applied to several types of organic compounds. Hydrocarbons give low yields of perfluoroalkanes. Alternatively, perfluoroalkanes may be prepared through reaction of functionalized substrates. Innert perfluorocyclic ethers are obtained from substrate ethers or acid fluorides. All types of amines perfluorinate but only perfluorotertiary amines are inert. Divalent organo-sulfur compounds afford inert perfluorinated products with sulfur in the hexavalent state. Sulfonyl fluorides give perfluorosulfonyl fluorides which can be pyrolytically coupled producing perfluoroalkanes. The Schoniger combustion method and neutron activation are described as analytical means for determining fluorine content.

Animals↗
PubMed1978

[Is there a possibility of paraplacental oxygenation of fetal blood? First results of an investigation with fluorocarbon (author's transl)].

By checking the cardiotropic effect on fetal rabbits we tried to find out weather there is a possibility of paraplacental oxygenation of fetal blood. Amniotic caves of nine fetal rabbits of 28th or 29th day of gestation are perfused with Perfluorobutyltetrahydrofuran (FX 80, 3 M Comp., St. Paul, Minn., USA) continuously. This was done by double blind investigation. The fetal heart rate is written by Hewlett-Packard-cardiotocograph. Therefore we use modificated EEG-electrodes. 48 h before we cut the spinal cord of the pregnant animals just for analgesie. So we exclude the influence of analgesics or narcotics. After complete interruption of uterine blood supply you can find an initial reduction of fetal heart rate. Using fluorocarbon we notice an increasing or stabilisation of fetal heart rate of all rabbit fetus. In comparison with control animals the difference is high significant. The cardial survival rate of four fetal rabbits treated with fluorocarbon is prolonged up to 50 min. During this time all "fluorocarbon fetus" never died earlier than the control animals. Lots of new questions are provoked by our results. One has to find an answer.

Animals↗
PubMed1988

Mechanical properties of fetal minipig lungs after substitution of surfactant with fluorocarbon and dipalmitoylphosphatidylcholine.

Respiratory distress syndrome (RDS) is characterized by quantitative and qualitative disturbances of surface active substances (surfactant). Therefore, intratracheal surfactant substitution is a favored subject of clinical investigations. In our study we tried to inflate and stabilize lungs in two steps: first, lungs were rinsed with a fluorocarbon and, second, artificially ventilated with a dipalmitoylphosphatidylcholine (DPPC) aerosol, the mean component of surfactant. Sixteen isolated fetal minipig lungs of day 95 (85% of the total gestation period) were used. From one pair of lungs one lung served as control (group 1), whereas the other was treated with DPPC (group II). In both groups the lungs were rinsed first with a fluorocarbon (FC-72, surface tension 12 mN/m). This maneuver was followed by an artificial ventilation with an aerosol of either salt solution (group I) or DPPC (group II) for 40 min. To characterize lung mechanics, static pressure volume curves were registered at 0, 20, and 40 min after fluorocarbon lavage. Airway opening pressure (pi), end-inspiratory volume (vi), and weight-specific end-inspiratory lung compliance (ci) were investigated. As biochemical parameters of the lungs we determined phospholipidphosphate content and DPPC, sphingomyelin (SM), and lysophosphaditylcholine (LPC) of the lung tissue. Significant differences were found with regard to phospholipidphosphate and DPPC content. No difference was seen in static pressure volume diagrams at the end of the investigation period.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Fluorocarbon-encapsulated oxygen bubbles for blood oxygenation use: an experimental study.

This paper is concerned with a novel class of oxygenators which Li and Asher first proposed and called "liquid membrane oxygenators." They are different from usual bubble blood oxygenators in that oxygen bubbles are individually encapsulated by a liquid fluorocarbon membrane and dispersed in blood, instead of bare oxygen bubbles normally used. The fluorocarbon membrane's role is to prevent direct contact of blood with oxygen gas which can cause a rupture of red blood cells and denaturation of proteins in blood. We have attempted to produce encapsulated bubbles by use of a fine double-tube nozzle where oxygen is supplied through the inner tube of the nozzle while a liquid fluorocarbon is supplied through the annular space between the outer and the inner tubes. This device has been found to enable steady formation, both in pure water and in an aqueous solution of bovine serum albumin, of encapsulated bubbles of about 2 mm in diameter, which are far smaller than those produced by Li and Asher's original device. A comparative study of oxygenation of water (a substitute for blood) by encapsulated bubbles and by nonencapsulated bubbles indicates that the former is only slightly inferior to the latter.

Biocompatible Materials↗
PubMed1991

Influence of intratracheal application of fluorocarbon 72 and different lipid-mixtures on mechanical behavior of isolated immature pig lungs.

Substitution of surfactant in immature lungs has two functional targets: the reduction of the overall alveolar surface tension and the mechanical stabilization of the system of alveoli having different diameters. Indeed, the lowering of the surface tension facilitates the inflation of the lungs, but according to Laplace's law small and large alveoli are not in pressure equilibrium as long as the surface tension is equal in both small and large alveoli. In the present work, we tried to stabilize the lungs and to compare the effect of bolus surfactant substitution with the two-step substitution of fluorocarbons and surfactant. In all, 24 fetal immature lungs were used. For our experiments we used fluorocarbon 72 (FC-72) with a surface tension of 12 mN/m. In groups 1 and 2, a mixture of dipalmitoylphosphatidylcholine (DPPC): cholesterol 9:1 (molar ratio) or DPPC: phosphatidylglycerol (PG) 9:1 (molar ratio) was administered intratracheally as a bolus. In the case of groups 3 and 4, the immature lungs were rinsed first with FC-72. After removing the fluorocarbon, the lungs were artificially ventilated and the DPPC: cholesterol 9:1 (group 3) or DPPC:PG 9:1 mixture (group 4) was given in aerosol form. Static pressure-volume curves (p-v) of the mean values of the 6 lungs in each group were registered at the beginning (0 min) and after 20 and 40 min of artificial ventilation. Airway opening pressure, weight-specific end-inspiratory lung compliance, and phospholipid contents were investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

The effect of fluorocarbon emulsion on 24-hour canine heart preservation by coronary perfusion.

This study was designed to evaluate the effects of fluorocarbon emulsion as an oxygen carrier in myocardial preservation. The hearts were preserved for 24 hours by coronary perfusion with either oxygenated crystalloid cardioplegic solution (group C) or crystalloid cardioplegic solution with fluorocarbon added (group FC). The perfusion pressure was kept at 20 mm Hg, and myocardial temperature was maintained at 4 degrees C. Group FC demonstrated better recovery in developed pressure and maximum rate of rise of left ventricular pressure compared with group C. The postpreservation end-diastolic pressure in group C increased significantly compared with the baseline value (value obtained before preservation). On the other hand, group FC showed no significant increase of end-diastolic pressure after preservation. Group FC released a significantly lower level of creatine kinase into its perfusate than did group C. Ultrastructural changes after preservation in group C showed severe ischemic injury, but there was no evidence of ischemic injury in group FC. The use of fluorocarbon emulsion proved beneficial to myocardial protection in long-term preservation of canine hearts.

Animals↗
PubMed1990

Cholesterol oxidation on fluorocarbon emulsion surface leads to the formation of 7-peroxycholesterol.

Formation of biologically active oxidized derivatives of cholesterol as a result of its oxidation on the surface of fluorocarbon emulsions was studied. A single product of cholesterol oxidation, 7-peroxycholesterol, was found. It was shown that 7-peroxycholesterol and its derivative 7-keto-cholesterol inhibit the rosette formation between human T-lymphocytes and sheep erythrocytes. These substances exert a strong cytostatic action on the growth of procaryotic and eucaryotic cell cultures. Thus, oxidative modification of blood plasma components on the surface of fluorocarbon emulsion particles with the formation of highly active compounds must be taken into account when using the fluorocarbon emulsions in medicine.

Acholeplasma laidlawii↗
PubMed1984

Genotoxicity and carcinogenicity of fluorocarbons: assessment by short-term in vitro tests and chronic exposure in rats.

Two short-term in vitro tests for mutagenicity (Salmonella reverse mutation and BHK21 cell transformation) were conducted on a series of fluorocarbons. Some of these materials (FC22, FC31, FC142b, FC143, and FC143a) were found to be positive in one or both of the tests and could therefore be considered as being potentially carcinogenic to animals. Such activity was not anticipated for what were previously considered inert materials and in consequence several examples of these fluorocarbons, which represented different combinations of short-term test results, were tested for carcinogenicity in limited in vivo bioassays. In these studies, rats were dosed for 1 year by gavage 5 days a week with either FC22, FC31, FC133a, FC134a, or FC143a dissolved in a corn-oil at a single dosage of 300 mg/kg body weight. The animals were then observed until week 125 with detailed necropsy at termination. The study revealed that FC31 was a potent carcinogen (to the rat stomach), a result which reflected the short-term test predictions, but FC133a, which gave a negative response in both the in vitro assays, induced a high incidence of reproductive tract tumors. The weak bacterial mutagens FC22 and FC143a did not induce tumors in this study, and the nonmutagenic FC134a was without overt carcinogenic activity. It is concluded that, while recognizing the limitations of the in vivo component of this study, the short-term tests were only partially successful in identifying potential carcinogens for this series of chemicals. Fluorocarbon 31 was a potent carcinogen which was first identified by bacterial mutation and cell transformation, whereas the equally potent carcinogen FC133a was not so identified. The lack of genotoxic activity with this particular compound leads us to believe that the carcinogenic activity may be due to mechanisms other than those which involve direct DNA interactions.

Animals↗
PubMed1980

Fluorocarbon perfusion medium applied to the isolated rat brain.

In order to overcome the disadvantages of erythrocytes and albumin, a totally synthetic medium for the perfusion of the isolated rat brain was developed. the perfusion medium was based upon Krebs-Henseleit solution and contained in addition a fluorocarbon (FC 43) for oxygen transport and a polyol (Pluronic F 68) to furnish emulsifying and oncotic properties. The physico-chemical properties of this fluorocarbon perfusion medium allowed perfusion of an isolated rat brain to continue for more than 7 hr, while the medium could be stored as a stock emulsion for several months. The appropriate function of the isolated perfused rat brain is demonstrated by the EEG and by various substrates of the energy metabolism. The suitability of the fluorocarbon medium for perfusion of an isolated rat brain preparation is discussed.

Animals↗
PubMed1999

Phase behavior of fluorocarbon and hydrocarbon double-chain hydroxylated and galactosylated amphiphiles and bolaamphiphiles. Long-term shelf-stability of their liposomes.

This paper describes the morphological characterization, by freeze-fracture electron microscopy, and the thermotropic phase behavior, by differential scanning calorimetry and/or X-ray scattering, of aqueous dispersions of various hydroxylated and galactosylated double-chain amphiphiles and bolaamphiphiles, several of them containing one or two hydrophobic fluorocarbon chains. Colloidal systems are observed in water with the hydroxylated hydrocarbon or fluorocarbon bolaamphiphiles only when they are dispersed with a co-amphiphile such as rac-1,2-dimyristoylphosphatidylcholine (DMPC) or rac-1,2-distearoylphosphatidylcholine (DSPC). Liposomes are formed providing the relative content of bolaamphiphiles does not exceed 20% mol. Most of these liposomes can be thermally sterilized and stored at room temperature for several months without any significant modification of their size and size distribution. The hydrocarbon galactosylated bolaamphiphile HO[C24][C12]Gal forms in water a lamellar phase (the gel to liquid-crystal phase transition is complete at 45 degrees C) and a Im3m cubic phase above 47 degrees C. The fluorocarbon HO[C24][F6C5]Gal analog displays a more complex and metastable phase behavior. The fluorinated non-bolaform galactosylated [F8C7][C16]AEGal and SerGal amphiphiles form lamellar phases in water. Low amounts (10% molar ratio) of the HO[C24][F6C5]Gal or HO[C24][C12]Gal bolaamphiphiles or of the single-headed [F8C7][C16]AEGal improve substantially the shelf-stability of reference phospholipon/cholesterol 2/1 liposomes. These liposomes when co-formulated with a single-headed amphiphile from the SerGal series are by far less stable.

Calorimetry, Differential Scanning↗
PubMed2001

Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research.

The specific properties of fluorocarbons, exceptional chemical and biological inertness, high gas-dissolving capacity, low surface tension, excellent spreading characteristics and high fluidity, have triggered numerous applications of these compounds in oxygen delivery. An injectable emulsion of fluorocarbon-in-water destined to deliver oxygen to tissues at risk of hypoxia has now completed Phase III clinical trials in Europe. A neat fluorocarbon is currently investigated in Phase II for treatment of acute respiratory failure by liquid ventilation. Fluorinated lipids and fluorinated surfactants can be used to elaborate and stabilize various colloidal systems, including different types of emulsions, vesicles and tubules, that also show promise for controlled release drug delivery.

Drug Delivery Systems↗
PubMed2000

Exchange transfusion with fluorocarbon for studying synaptically evoked optical signal in rat cortex.

Optical imaging of intrinsic signal is a powerful technique for studying the functional organization of the brain [T. Bonhoeffer, D. S. Kim, D. Malonek, D. Shoham, A. Grinvald, Optical imaging of the layout of functional domains in area 17 and across the area 17/18 border in cat visual cortex, Eur. J. Neurosci. 7 (1995) 1973-1988; M. Hubener, D. Shoham, A. Grinvald, T. Bonhoeffer, Spatial relationships among three columnar systems in cat area 17, J. Neurosci. 17 (1997) 9270-9284; D. Malonek, A. Grinvald, Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping, Science 272 (1996) 551-554; A. Shmuel, A. Grinvald, Functional organization for direction of motion and its relationship to orientation maps in cat area 18, J. Neurosci. 16 (1996) 6945-6964] [1] [10] [14] [22]. Three components of intrinsic optical signal can be distinguished. Two of these components can be attributed either to changes in blood volume or to changes in oxygen consumption [R.D. Frostig, E.E. Lieke, D.Y. Ts'o, A. Grinvald, Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high resolution optical imaging of intrinsic signals, Proc. Natl. Acad. Sci. U. S. A. 87 (1990) 6082-6086] [7]. The origin of the third component is not yet clear but the component seems to be based on scattered light [H.U. Dodt, G. D'Arcangelo, E. Pestel, W. Zieglgansberger, The spread of excitation in neocortical columns visualized with infrared-dark field videomicroscopy, NeuroReport 7 (1996) 1553-1558; K. Holthoff, O.W. Witte, Intrinsic optical signals in rat neocortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space, J. Neurosci. 16 (1996) 2740-2749; B.A. MacVicar, D. Hochman, Imaging of synaptically evoked intrinsic optical signals in hippocampal slices, J. Neurosci. 11 (1991) 1458-1469; L. Trachsel, H.U. Dodt, W. Zieglgansberger, The intrinsic optical signal evoked by chiasm stimulation in the rat suprachiasmatic nuclei exhibits GABAergic day-night variation, Eur. J. Neurosci. 8 (1996) 319-328] [3] [9] [13] [24]. A spectral fitting method with three components is used for the analysis of intrinsic optical signal [M. Nemoto, Y. Nomura, C. Sato, M. Tamura, K. Houkin, I. Koyanagi, H. Abe, Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation, J. Cereb. Blood Flow Metab. 19 (1999) 246-259] [17]. In order to validate the analysis, we need the knowledge on contribution of signal resulted from hemoglobin to total intrinsic optical signal. The exchange transfusion with fluorocarbon has the advantage that can change the spectral contribution of hemoglobin [M. Ferrari, M.A. Williams, D.A. Wilson, N.V. Thakor, R.J. Traystman, D.F. Hanley, Cat brain cytochrome-c oxidase redox changes induced by hypoxia after blood-fluorocarbon exchange transfusion, Am. J. Physiol. 269 (1995) H417-H424; A.L. Sylvia, C.A. Piantadosi, O(2) dependence of in vivo brain cytochrome redox responses and energy metabolism in bloodless rats, J. Cereb. Blood Flow Metab. 8 (1988) 163-172] [6] [23]. Here we describe a new method of the reduction of hemoglobin signal from somatosensory evoked optical intrinsic signal in rat cortex by the combination of exchange transfusion with fluorocarbon and imaging system of thinned skull cranial window. The method allows for the study of the synaptically evoked changes in light scattering as well as fluorescence of calcium indicator or voltage-sensitive dye without absorption of hemoglobin.

Animals↗