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Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local PO2 and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant PO2, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.

We evaluated the toxicity of perfluorooctylbromide in the primate eye as a short-term postoperative vitreous substitute. Four eyes of 4 African green monkeys underwent complete vitrectomy and vitreous replacement with 1.5-2.0 ml of PFOB. One additional animal received BSS as a control vitreous substitute in one eye. Animals were examined twice weekly for clarity and consistency of the vitreous replacement substance. Anterior segment and lenses remained clear in all eyes, although in the immediate postoperative period one eye became inflamed and had a culture-negative vitritis. The other eyes showed a minimal anticipated postoperative vitreous inflammation. Emulsification of the PFOB began within 3 days of injection and progressed up to 3 weeks, precluding fundus examination and fluorescein angiography after 2 weeks. Eyes were enucleated and light microscopy performed at 2 days, 10 days, 33 days, and 45 days. No toxic effects to the retinal cells were detectable by histological examination, but perivasculitis of retinal vessels was noted at 45 days. Indirect examination was normal up to 10 days; thereafter, the fundus view was obscured by the emulsified PFOB. Because of cellular migration into the vitreous cavity and retinal perivasculitis, observed histologically, PFOB seems most suitable for intraoperative rather than postoperative use.

Two preparations of silicone gels were evaluated as long-term vitreous substitutes in the vitrectomized and lensectomized eyes of primates. Both preparations were injected in liquid form and polymerized in the vitreous cavity. There was no toxic effect on the ocular structures up to 13 months after implantation. Fundus examination and fluorescein angiography were possible through the less rigid gel, whereas the preparation with higher rigidity consistently appeared cloudy.

Eight adult New Zealand Swiss rabbits (3-5 kg) having previously implanted chronic bilateral platinum electrodes in the visual cerebral cortex and subcutaneous silver reference electrodes were tranquilized and monitored in multiple 2-3 hour sessions using voltammetric techniques. Six of these were given intratracheal neat liquid fluorocarbons ranging in boiling point from 132 degrees C to 215 degrees C at doses of 2 or 4cc/kg. Each animal received only one fluorocarbon liquid. Two additional rabbits were match-studied as controls. Half of the rabbits have survived more than five months. Both controls and two experimental rabbits were sacrificed after more than seven months due to gastric hairballs. The period of daytime monitoring sessions, when cathodic brain oxygen currents (aO2), arterial blood gases and pH were obtained, was between 34 and 263 days. In some animals the arterial pCO2 was increased during the first week but the pO2 and pH remained nearly normal in all eight animals throughout. The two best fluorocarbons for liquid breathing on the basis of this limited but intensive work are F-methyldecalin and F-5,6H-dec-5-ene (F44E).

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.

Six African green monkeys (six eyes) underwent vitrectomy and vitreous replacement with Vitreon® (perfluorophenanthrene) or Vitreon plus silicone. A seventh animal served as a control. Vitreon alone and in combination remained optically clear and allowed fundus examination up to 162 days. No toxic effects to the retina were detectable. Vitreon exhibited some degree of emulsification and formed some globules at 45 days postoperatively. Interestingly, Vitreon emulsification occurred at a later time (80 days) in one of the silicone plus Vitreon eyes. The combination of silicone plus Vitreon may offer the advantage of tamponading the inferior and superior retina in phakic eyes.

Over 100 perfluorinated organic substances (PFS) oxygen solvents and 80 surfactants have been tested in emulsions for possible use as artificial blood. Most PFS are too toxic, will not form stable emulsions, have too high a vapor pressure, or become firmly attached to the liver, where they are found in both Kupffer cells and hepatocytes. The most promising emulsifiers are Pluronic F68 and Vitrum egg phospholipid. Perfluoromethyldecalin, perfluorodecalin, and perfluorodimethyladamantane are cyclic PFS which are nontoxic oxygen solvents and which are only temporarily retained in the liver. Most straight chain fluorocarbons (C10 or less)—either completely fluorinated or containing terminal hydrogens, bromine, or iodine—are found to leave the liver within periods of 2 wk to several months. Physiologically useful water soluble PFS are reported here for the first time. Although animals survive in apparent health for years with large amounts of certain PFS in the liver and spleen, such linkage indicates a definite reaction with tissue. Therefore, it seems better to avoid using these compounds for organ perfusion and as clinical blood substitutes. We show by extensive morphological examination by light and electron microscopy, that perfluorodecalins produce no changes in the ultrastructure of the liver. PFS that leave the liver and also contain iodine or bromine atoms are radiopaque oxygen solvents useful as diagnostic agents and in microvascular research under various physiological conditions.

Perfluorophenanthrene, a liquid fluorocarbon with a specific gravity approximately twice that of water, potentially offers certain advantages as a vitreous substitute in vitreoretinal surgery. To determine its efficacy and safety we first purified it by chemical methods used in the preparation of experimental blood substitutes to a level at which it was not at all or only minimally toxic to culture-grown retinoblastoma cells. Nineteen of 22 vitrectomized eyes of white New Zealand rabbits injected with this purified perfluorophenanthrene showed satisfactory clinical tolerance. Light and electron microscopy showed minimal or no toxic effects in the 19 eyes, although uptake of perfluorophenanthrene by some preretinal cells was observed 28 days after implantation. Postoperative light-adapted electroretinography recordings of eight of the injected eyes showed no significant change. Perfluorophenanthrene injected into the anterior chamber of the rabbit eyes had toxic effects on the cornea. If further experimentations confirm our findings, perfluorophenanthrene may be a suitable transparent high-density liquid for temporary use in surgery to repair retinal detachments.

A new lactate sensor makes it possible to measure the lactate content of whole blood directly in less than 1 min, using only a 10-microL blood sample. The procedure works equally well with plasma, serum, spinal fluid, other body fluids, or tissue homogenates. The instrument is calibrated with lactate standards between 0 and 15 mMol/L. The sensor, a polarographic enzyme electrode, gives a current which is a linear function of the lactate concentration. There is no interference from glucose, pyruvate, alcohol, ascorbate, anticoagulants, lidocaine, acetaminophen, or other drugs and metabolites commonly encountered in critically ill patients. The lactate sensor is composed of a peroxide sensor and an enzyme transducer membrane. The lactate is stoichiometrically converted to pyruvate and hydrogen peroxide by lactate oxygen oxidoreductase derived from Pediococcus species. The oxygen required for the enzymatic oxidation is supplied via an air-permeable silicone elastomeric membrane used for stirring. Comparison of our new electroenzymatic method with the Boehringer-Mannheim photoenzymatic method gives correlations of 0.997 for both whole blood and plasma.

Synthese de dineopentyl-, diisopentyl- et diisopropyl ethers perfluores (utilisables comme succedane du sang)

Solubility of gases, especially oxygen, in fluorocarbons has achieved important status because of the latter's probable utility in artificial blood and liquid breathing, but only diverse data determined by various methods is scattered throughout the literature and company technical reports. One method, gas chromatography, was used to calculate and compare the oxygen and air solubility of a large number of fluorocarbons. Correlations were made between the oxygen solubilities and some of the physical properties of the compounds. Likewise, solubilities calculated using some lower parachor values resulted in a fairly good correlation.

Nuclear magnetic resonance(NMR)imaging of perfluorocarbon (PFC) emulsions and neat liquids has shown potential for i n v i v o oxygen imaging in blood and organ tissue. PFC compounds exhibit complicated NMR spectra caused by chemical shifts and spin–spin couplings which can lead to artifacts and degraded spatial resolution of resulting NMRimages. To correct for the chemical shift artifacts, the technique of spectral deconvolution has been applied to NMR imaging of PFC compounds. The temporal filter for this process can be directly applied to raw free induction decay data in projection reconstruction or to spin‐echo data in two‐dimensional Fourier transform imaging techniques. The effect of chemical shift artifacts was demonstrated through the NMR imaging of two PFC compounds (F‐tributylamine and F‐decalin) in phantoms. Methods are presented and demonstrated which allow the chemical shift artifacts to be removed and true images of the spatial distribution of the PFC’s to be recovered.

Fluorocarbons (fluorinated organic compounds in which O2 and CO2 are highly soluble) have been shown to be effective substitutes for the gas transport functions of blood. In order to investigate the effects of fluorocarbons on acute regional myocardial ischemia, we compared the rise of intramyocardial pCO2 (ΔPm CO2) and the decline in intramyocardial pO2 (nadir PmO2) produced by paired, temporary coronary artery occlusions (CAO) in anesthetized dogs instrumented with mass spectrometer probes positioned in ischemic myocardium. In protocol A (n = 7) dogs were ventilated with 100% O2 alone during the first CAO and received fluorocarbons (perfluorochemicals, PFC) 40 ml/kg intravenously in addition to O2 before a second CAO: ΔPmCO2 fell from 32.8 ± 4.7 to 23.3 ± 3.9 mm Hg (p < 0.05) and the nadir PmO2 was higher during the second CAO (21.6 ± 7.4 mm Hg) than during the first (9.4 ± 3.9 mm Hg, p < 0.05). In six dogs in protocol B also ventilated with 100% O2, 40 ml/kg normal saline was infused before the second occlusion, but this did not alter the response to CAO. Thus the degree of volume expansion produced by PFCs did not reduce ischemia in dogs ventilated with 100% O2. Subsequent studies were undertaken to determine whether circulating PFCs ameliorated acute ischemic injury in dogs ventilated with ambient air. In eight dogs in protocol C, ΔPmCO2 was decreased after PFC administration; however, nadir PmO2s were not altered by PFC; in seven dogs in protocol D receiving only normal saline between CAOs, there were no differences in myocardial gas tension. There were no changes in myocardial blood flow to the central ischemic zone between CAOs in any experimental group. We conclude that circulating PFCs reduce acute regional myocardial ischemia during ventilation with either 100% O2 or ambient air, and that PFC-O2 treatment augments myocardial O2 availability in the central ischemic zone. The mechanisms by which PFC-O2 and PFC administration reduce ischemic injury are likely multifactorial, combining elements of enhanced O2 supply and decreased myocardial O2 demand.

SummaryA new method of blood oxygenation by gas dispersion was tested by subjecting dogs, under local anesthesia and morphine sedation, to conditions of complete anoxic anoxia by substituting pure nitrogen for air as the respiratory gas for about one hour.If a minimum blood flow of approximately 40 ml/kg/min was maintained, the animals survived the experiment without loss of consciousness, and recovered completely without exhibiting any neurological signs of anoxic damage.

A child, studied between the ages of 1½ and 3½ years, presented an abnormally low plasma alkaline phosphatase activity (0.8-1.64 Bessey-Lowry u.), a deformed skeleton and the loss of most of her deciduous teeth. The serum Ca was normal; the serum inorganic phosphate remained at the normal relatively high levels of infancy as the child grew older Roentgenograms demonstrated deficient mineralization of the skeleton and teeth. Biopsies of the liver and the costochondral junction displayed a deficiency of tissue alkaline phosphatase activity. The architecture of the rib was consistent with rickets. There was no evidence for the presence of an inhibitor of alkaline phosphatase, such as beryllium, or for an excessive excretion of the enzyme. Treatment with purified growth hormone, ascorbic acid and thiamin chloride had no effect, while vitamin D 500 thousand u. caused little change in the enzyme activity in a 10 day period. The father had low plasma alkaline phosphatase activity and a number of similar patients are mentioned, for whom there was also evidence that the deficiency in alkaline phosphatase activity may be genetically determined. While the precise role of alkaline phosphatase activity in the metabolism of bone is not clear, the findings in this patient suggest that growing bone may require the presence of alkaline phosphatase for normal calcification, and that the skeletal disorder, which could not be distinguished from rickets, may be related to a disturbance in the local factor.

Summary Plasma alkaline phosphatase is high in infancy, then drops by the second year of life to a plateau which lasts until pubescence. At 9 years of age in girls and 11 years of age in boys a rapid drop occurs, until by the seventeenth year of life adult values are found. The sex difference which begins at pubescence diminishes gradually until the age of 20 but persists into adulthood, in male subjects higher than in female. The plasma alkaline phosphatase activity seems to be closely related to growth rate as indicated by height measurements and to be derived largely from osteoid tissue as indicated by taurocholate inhibition studies.

The excretion of creatine and creatinine in 280 urine samples from 36 subjects during the course of uncomplicated pregnancies has been studied. Creatinine excretion averaged 1.21 Gm. per 24 hours with a standard deviation of 0.19. The average woman excretes 19.1 mg. of creatinine per kilogram of body weight per day, a value which does not increase, and may even drop somewhat, during pregnancy. The average creatine excretion is 0.24 Gm. per day with values starting at 0.15 Gm. per day in the third lunar month, increasing to a peak of 0.33 at the seventh lunar month, and dropping to 0.22 by the tenth month and to about 0.15 by the first month post partum. The excretion of 17-ketosteroids is significantly higher in those women who excrete large amounts of creatinine, while the basal metabolic rate is higher in those women who excrete larger amounts of creatine. No explanation could be found for the high week-to-week variability in creatine excretion.

A large capacity all‐Pyrex dispersion oxygenator and pump is described which is capable of substituting temporarily for the function of the heart and lungs. Blood is oxygenated by tiny bubbles of oxygen dispersed in the blood. These bubbles are coalesced on a polymethylsiloaxane surface and eliminated in a bubble trap which also serves as the pumping chamber. Pumping is accomplished by an alternating suction and pressure controlled by two electrodes, suspended in the chamber, which actuate two solenoid valves. The apparatus causes no significant damage to the red blood cells. The apparatus is portable, easily cleaned and sterilized, and inexpensive. Oxygenation, carbon dioxide elimination, temperature, pulsation rate and pressure, flow, and mean pressure can be controlled for various physiological studies. The blood volume of the apparatus is constant except for the stroke volume and in this respect resembles the normal heart.

Insulated metal polarographic cathodes were permanently implanted in the brains of cats, allowing continuous recording of oxygen availability. A study was made of the current flow as related to app...

Open-chest, anesthetized dogs with occlusions of the left anterior descending coronary artery breathed 100 percent oxygen while they were bled to a hematocrit of 25 percent and infused with an approximately equal volume (40 milliliters per kilogram) of fluorocarbon preparation or Ringer solution. Dogs breathing room air and receiving no treatment served as controls. After undergoing 6 hours of coronary occlusion, animals bled and treated with fluorocarbons developed smaller infarctions than those receiving Ringer solution or no treatment.

Perfluorinated organic liquids are useful as high capacity oxygen and carbon dioxide solvents. After intravenous infusion most of these perfluorinated emulsions are deposited in the liver and spleen in a matter of days, where they remain for the lifetime of the animal. Hence, while they may be useful as isolated organ perfusion media their value as artificial blood is limited. A family of perfluorocarbons has now been discovered, which, although deposited in the liver after circulation in the blood, leave the liver to be excreted via the lungs and skin in a matter of days without apparent harmn to the animal.