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Plasma gas discharge deposited fluorocarbon polymers exhibit reduced elutability of adsorbed albumin and fibrinogen.

The adsorption and subsequent detergent elutability of fibrinogen and albumin were measured on various treated and untreated polymer films in order to determine whether the relative adsorption of these proteins was responsible for the enhanced thromboresistance of Dacron vascular grafts treated with tetrafluoroethylene in a radio frequency glow discharge (RFGD) apparatus. Fluorocarbon-coated surfaces varying in the relative proportions of CF, CF2, and CF3 groups and in the ratio of fluorine to carbon were prepared by RFGD treatment of poly(ethylene terephthalate) (PET) films with tetrafluoroethylene or perfluoropropane. The adsorption of fibrinogen and albumin to these fluorocarbon-coated surfaces was comparable to the adsorption of the proteins to polytetrafluoroethylene (PTFE) and PET. However, the elutability of fibrinogen and albumin from the RFGD fluorocarbon surfaces with sodium dodecyl sulfate was much lower than that from PTFE or PET. Other RFGD treatments of PET, such as ethylene deposition or argon etching, did not reduce the extent of albumin elutability as dramatically as did the RFGD fluorocarbon treatments. The strong albumin binding to RFGD fluorocarbon surfaces may be exploited clinically to enhance the retention of albumin preadsorbed to blood-contacting surfaces to render them thromboresistant.

Adsorption↗

Fluorocarbon-based oxygen carriers: new orientations.

Fluosol, a first, low-concentration fluorocarbon emulsion, was recently approved for oxygenating the myocardium during percutaneous transluminal coronary angioplasty. Improvements in fluorocarbon and emulsion technology have led to the development of significantly more stable, more efficient second-generation injectable O2 carriers. This progress extends the potential of fluorocarbons in medicine to new applications both in diagnostics and in therapeutics. Future objectives will aim at adjusting and optimizing the preparation's characteristics for each specific application. The emulsifier, or surfactant, which determines the external appearance of the fluorocarbon droplets, will play a key role in the mastery of emulsion properties. Extensive research efforts are therefore being directed toward the synthesis and evaluation of new families of surfactants or co-surfactants specifically designed for emulsifying fluorocarbons.

Blood Substitutes↗

[The experimental study on long-term cardiac preservation: the efficacy of low-flow continuous perfusion with fluorocarbon].

We compared the effect of simple immersion and continuous perfusion on long-term cardiac preservation, and evaluated the effectiveness of perfusion with oxygenated fluorocarbon solution. The isolated rabbit hearts were preserved for 24 hours at 4 degrees C using the following five preservation techniques: (1) simple immersion with Collins M solution (Group I), (2) perfusion with oxygenated Collins M solution at a flow rate of 10 ml/hr (Group II), (3) perfusion with the same solution as in Group II at a flow rate of 20 ml/hr (Group III), (4) perfusion with oxygenated Collins M solution containing 10% fluorocarbon at a flow rate of 10 ml/hr (Group IV), (5) perfusion with the same solution as in Group IV at a flow rate of 20 ml/hr (Group V). The hearts of Group I showed a significant decrease of myocardial ATP and an increase of myocardial lactate during preservation compared to the hearts of perfusion groups. Assessment of isovolumic left ventricular function following 24-hour preservation using a support animal showed a significant decrease of Max dp/dt and increase of end-diastolic pressure in the hearts of Group I. Perfusion with fluorocarbon (Group IV and V) significantly increased oxygen consumption compared to Group II and III in association with minimum accumulation of myocardial lactate, indicating that aerobic metabolism during preservation is better maintained in the fluorocarbon-perfused hearts. Moreover, CPK release and myocardial water gain during preservation were significantly less, and left ventricular function following preservation was significantly better in these hearts. Increasing the flow rate from 10 ml/hr to 20 ml/hr resulted in sustained increase in perfusion pressure (1.80 +/- 0.53 to 3.70 +/- 0.34 mmHg) and myocardial water content (79.2 +/- 0.4 to 87.2 +/- 0.3%) during preservation in the hearts of Group III, but it did not further improve left ventricular function despite significant enhancement of myocardial oxygen uptake in both Group III and V. These results suggest that hypothermic low-flow continuous perfusion with oxygenated Collins M solution is superior to simple immersion with the same solution for long-term cardiac preservation, and that the addition of fluorocarbon to the perfusate enhances the efficacy of such a perfusion.

Animals↗

Ischemic myocardial protection. Comparison of nonoxygenated crystalloid, oxygenated crystalloid, and oxygenated fluorocarbon cardioplegic solutions.

This study was designed to compare myocardial protection with a nonoxygenated crystalloid solution, an oxygenated crystalloid solution, and an oxygenated fluorocarbon cardioplegic solution. Postischemic ventricular performance was studied in three equal (N = 7) groups of dogs subjected to 120 minutes of global ischemia induced at an average myocardial temperature of 18.5 degrees +/- 1.4 degrees C (range 17.0 degrees to 21.0 degrees C). Left ventricular global and regional function was evaluated by sonomicrometry and micromanometers before ischemia and at 45 and 60 minutes after ischemia. Stroke volume index, left ventricular pressure-minor external diameter loop area, percent shortening, first derivative of left ventricular pressure, mean velocity of circumferential fiber shortening, and the slope of the end-systolic pressure were used to evaluate myocardial contractility. In vitro oxygen content of the three cardioplegic solutions was measured at a mean injection temperature of 8.3 degrees +/- 0.6 degrees C: 0.8 +/- 0.1 vol% (nonoxygenated crystalloid cardioplegia), 3.2 +/- 0.2 vol% (oxygenated crystalloid cardioplegia), and 6.2 +/- 0.2 vol% (oxygenated fluorocarbon cardioplegia). Recovery of global and regional function was significantly (p less than 0.05) better with both oxygenated solutions than with the nonoxygenated solution. Differences between the oxygenated crystalloid and fluorocarbon groups were not significant. We conclude: (1) Compared to nonoxygenated crystalloid cardioplegia, oxygenated crystalloid and oxygenated fluorocarbon cardioplegic solutions gave superior myocardial protection during 2 hours of ischemic arrest; (2) no difference was found in protective effects between an oxygenated crystalloid and an oxygenated fluorocarbon solution.

Animals↗

Fluorocarbon and dextran hemodilution in myocardial ischemia.

The effect of hemodilution, with a fluorocarbon erythrocyte substitute and with dextran, on myocardial ischemia induced by occlusion of the left anterior descending coronary artery was investigated in anesthetized dogs. The resulting changes were compared to those in a control group subjected to a sham-exchange procedure. The hematocrit was reduced to 23% to 26% by dilution with fluorocarbon and dextran, while it was maintained at 42% to 46% in the control group. At similar hematocrit levels, during ventilation with 100% oxygen, the fluorocarbon-diluted blood transported 4 ml/dl more oxygen in the plasma phase than the dextran-diluted blood. Left ventricular function was not significantly altered and there was a marked improvement of blood flow to the ischemic zone. The mass of dehydrogenase-stained ischemic myocardium (21% of left ventricular mass) was marginally (p less than 0.06) smaller in the dogs with fluorocarbon-diluted blood than in the control group (29% of left ventricular mass). The output of creatine phosphokinase by the heart was also reduced (p less than 0.05) by hemodilution with fluorocarbon. These findings suggest that hemodilution with an oxygen-transporting blood substitute may have marginal beneficial effects on the collateral perfusion of acutely ischemic myocardium following sudden coronary artery occlusion.

Animals↗

Fluorocarbon aerosol propellants XII: Correlation of blood level of trichloromonofluoromethane to cardiovascular and respiratory responses in anesthetized dogs.

Anesthetized mongrel dogs were exposed to various concentrations of trichloromonofluoromethane. Before, during, and after the inhalation, arterial and venous blood samples were obtained for fluorocarbon analysis. After the cessation of fluorocarbon inhalation, a multiexponential decline for the blood was observed. This finding was similar to that of previous study in which the fluorocarbon was administered intravenously to unanesthetized dogs. The half-life calculated from the terminal phase was about 280 min, and the pseudodistribution equilibrium was reached about 100 min after dosing. Study of the relationship between blood fluorocarbon levels and effects on the respiration rate and arterial blood pressure indicates that the sites of these pharmacological activities are located in the blood or central compartment rather than in the peripheral compartment. The effect on the heart rate appears to be quite instantaneous after inhalation. These results might shed some light on the fast effect of the fluorocarbon propellants, which caused sudden deaths after inhalation of a large quantity.

Aerosol Propellants↗

Cardiovascular effects of acute and chronic inhalations of fluorocarbon 12 in rabbits.

The effects of inhaling fluorocarbon 12, a common propellant in household aerosols, were studied in closed-chested rabbits. Inhalation of 10 or 20% fluorocarbon 12 produced a decline in cardiac output and a dose-related depression of peak left ventricular (LV) dP/dt without associated arrthythmias, hypoxemia or significant changes in LV end-diastolicpressue or heart rate. There was a small decline in LV systolic pressure without a significant drop in mean arterial pressure. Breathing fluorocarbon 12 for 30 minutes caused a decline in peak LV dP/dt, cardiac output, LV systolic pressure and mean arterial pressure which was present throughout the exposure period. The effects observed during acute fluorocarbon 12 exposure were not altered by previous chronic, intermittent exposure to 10% fluorocarbon 12.

Aerosol Propellants↗

Mechanical properties of isolated fetal miniature pig lungs after substitution with fluorocarbons.

In our present study we tried to inflate and stabilize isolated immature lungs of fetal minipigs in gestation age of 95 days (= 85% of total normal gestation period) with different fluorocarbons. Based on our previous experiences, the immature lungs at day 95 are almost non inflatable with air. For our experiments we used fluorocarbon 43 (FC-43) with a surface tension of 16 mN/m and fluorocarbon 72 (FC-72) with a surface tension of 12 mN/m. Eighteen fetal immature lungs were used. In group 1 the lungs were rinsed with FC-43; in group 2 the rinse solution was FC-72, and in group 3 the lungs were untreated. After removing the fluorocarbon, in the case of groups 1 and 2, the lungs were artificially ventilated. Pressure-volume (p-v) curves were registered in the beginning (immediately after FC lavage), after 10 and 20 min of artificial ventilation. Airway opening pressure (pi) and weight-specific end-inspiratory lung compliance (ci) were investigated. Statistically significant differences in weight-specific end-inspiratory compliance were found between FC groups and untreated group 3, but no stabilization could be seen during the investigation period of 20 min. No statistically significant improvement in weight-specific end-inspiratory compliance was observed between group 1 and 2, although the compliances of group 2 with FC-72 were better than those of group 1 with FC-43 in three p-v diagrams registered in the beginning and after 10 and 20 min of artificial ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of fluorocarbons with and without oxygen supplementation on cardiac hemodynamics and energetics.

Because of uncertainty about the mechanism by which fluorocarbons ameliorate myocardial ischemia, the effects of a fluorocarbon emulsion, perfluorodecalin and perfluorotripropylamine (Fluosol-DA 20% TM) with and without 100% O2 inhalation, on cardiac hemodynamics and energetics were studied in the anesthetized dog. Left ventricular (LV) intramural partial pressure of oxygen (PmO2) was measured by mass spectrometry before and after intravenous infusion of Fluosol-DA 20% (40 ml/kg), and was compared with measurements made in another group of dogs receiving the volume expander dextran (36 ml/kg). Both groups of dogs were then ventilated with 100% O2 and repeat measurements were performed. In the 11 animals receiving fluorocarbons, there were increases in left atrial pressure, LV myocardial blood flow, and LV myocardial O2 consumption (MVO2) compatible with volume expansion. After 100% O2, LV MVO2 decreased to control values, while PmO2 increased to 127 +/- 48 mm Hg (p less than 0.001). There were no significant changes in heart rate, arterial pressure or first derivative of LV pressure (dP/dt) during the study. In 10 dogs treated with dextran there was no change in heart rate or dP/dt, but arterial and left atrial pressures were higher after dextran infusion and remained elevated after 100% O2 inhalation. LV MVO2 increased with volume expansion, and remained increased after 100% O2. PmO2 (66 +/- 18 mm Hg) after 100% O2 was lower (p less than 0.02) than in the fluorocarbon-treated dogs after O2 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fluorocarbon cardioplegia and myocardial protection.

This study compares myocardial protection using nonoxygenated clear cardioplegia with oxygen-carrying solutions of blood (PO2, 100 mm Hg) and fluorocarbon (FC-47 perfluorotributylamine, PO2, 500 mm Hg), all containing 25 mEq/L of potassium chloride. Three groups of dogs, each consisting of 5 animals, were placed on cardiopulmonary bypass, and the aorta of each dog was cross-clamped for 45 minutes. Hemodynamic and biochemical variables were measured at baseline and during recovery. Levels of the myocardial isoenzyme of creatine phosphokinase (CPK-MB) in the coronary sinus were significantly lower in the fluorocarbon cardioplegia group at 15 minutes of aortic cross-clamping (p less than 0.01), while both the fluorocarbon and blood cardioplegia groups demonstrated lower CPK-MB levels at 45 minutes (p less than 0.001 and p less than 0.05, respectively), compared with the clear cardioplegia group. The blood and fluorocarbon groups had improved mean aortic blood pressure (p less than 0.02 and p less than 0.05, respectively) and left ventricular pressure. At 45 minutes of reperfusion and recovery, all hemodynamic and enzymatic variables were similar in each group. We conclude that oxygenated solutions better protect the myocardial cell, but that further work is needed to determine the most effective oxygen level for maximum protection with cardioplegia.

Animals↗

Influence of fluorocarbon emulsions on porphyrin-sensitised oxidation of histidine.

The influence of fluorocarbon emulsions on the efficiency of photosensitized oxidation of histidine in solution has been studied, using haematoporphyrin and dihaematoporphyrin derivatives as sensitisers. It is shown that the fluorocarbon emulsions at low concentrations efficiently disaggregate porphyrins, and thereby enhance photosensitised oxidation. The high solubility of oxygen in fluorocarbon emulsions maintains solution oxygen tension, optimising photooxidative damage. It is suggested that fluorocarbon emulsions might find a role in photodynamic therapy, both as carriers for sensitising dyes, and also to maintain tissue oxygenation in hypoxic regions of solid tumours.

Emulsions↗

Predictions of capillary oxygen transport in the presence of fluorocarbon additives.

A mathematical model of capillary oxygen transport was formulated to determine the effect of increasing plasma solubility, e.g., by the addition of an intravascular fluorocarbon emulsion. The effect of increased plasma solubility is studied for two distributions of fluorocarbon, when the fluorocarbon droplets are uniformly distributed throughout the plasma and when the fluorocarbon droplets are concentrated in a layer adjacent to the endothelium. The model was applied to working hamster retractor muscle at normal and lowered hematocrit. The intracapillary mass transfer coefficient was found to increase by 18% as the solubility was increased by a factor of 1.7 at a hematocrit of 43%. An additional increase of 6% was predicted when the solubility increase was concentrated in the layer adjacent to the endothelium. At a hematocrit of 25%, the intracapillary mass transfer coefficient increased 14% when the solubility was increased by a factor of 1.7.

Animals↗

The efficacy of fluorocarbon, surfactant, and their combination for improving acute lung injury induced by intratracheal acidified infant formula.

We conducted the current study to compare the efficacy of partial liquid ventilation (PLV), pulmonary surfactant (PSF), and their combination in ameliorating the acidified infant-formula-induced acute lung injury (ALI). In the Part I study, 42 rabbits receiving volume-controlled ventilation with positive end-expiratory pressure 10 cm H(2)O were randomly divided into 6 groups (groups noninjuryI, gas ventilation [GVi], PLVi, PSFi, PLVi-->PSFi, and PSFi-->PLVi). ALI was induced by intratracheal acidified infant formula (2 mL/kg, pH 1.8). Group GVi received neither PLV nor PSF therapy. Groups PLV and PSF received intratracheal fluorocarbon 15 mL/kg or surfactant 100 mg/kg, respectively, 30 min after acidified infant formula. Groups PLVi-->PSFi and PSFi-->PLVi received both treatments at 30-min intervals. In Part II, 42 rabbits (in 6 groups) undergoing pressure-controlled ventilation received the same drug therapies as in Part I. The lungs were excised to assess biochemical and histological damage 150 min after induction of ALI. In Parts I and II, PSF, fluorocarbon, and their combination attenuated lung leukosequestration and edema and superoxide production of neutrophils, consequently improving oxygenation, lung mechanics, and pathological changes. Independent of ventilation mode, PSF followed by fluorocarbon provided the most beneficial effects and fluorocarbon followed by PSF produced the least efficacy.

Acids↗

Preservation of neuronal function during prolonged focal cerebral ischemia by ventriculocisternal perfusion with oxygenated fluorocarbon emulsion.

The left middle cerebral artery and both carotid arteries of 17 cats were occluded to evaluate the effects of oxygenated fluorocarbon emulsion on brain ischemia. Carotid and middle cerebral arteries were occluded concurrently for 2 hours, followed by occlusion of the middle cerebral artery only for another 24 hours. Six animals were treated with oxygenated fluorocarbon emulsion delivered by ventriculocisternal perfusion, 5 received ventriculocisternal perfusion with mock cerebrospinal fluid, and 6 were untreated. Perfusions were started 3 hours after the initial ischemic insult. Infarct size judged by tetrazolium staining and standard neuropathological stains was significantly smaller in the treated animals. The mechanism of protection is as yet unknown, but most likely reflects oxygen/nutrient diffusion into the ischemic middle cerebral artery zone from the ventricular fluorocarbon, or removal of harmful metabolites. The results imply that ventriculocisternal perfusion with fluorocarbon emulsion can preserve neuronal function during a major cerebral vessel occlusion. In the cat, therapy is effective if begun within 3 hours after ischemia starts.

Animals↗

Effect of fluorocarbon perfusion upon the preservation of amputated limbs. An experimental study.

The present study was undertaken to investigate the effect of fluorocarbon on the preservation of an amputated limb. The hind limbs of dogs were completely amputated through the mid-thigh; some were perfused with fluorocarbon, others with lactated Ringer's solution and some were not perfused at all. After six hours of ischaemia, all the limbs were replanted. Perfusion with fluorocarbon had an inhibitory effect on the anaerobic metabolism of an amputated limb, thus increasing the survival rate. Leakage of creatine phosphokinase from the replanted limb also was inhibited by perfusion with fluorocarbon. These effects were more striking when the amputated limb was perfused continuously rather than intermittently and when it was preserved in iced water rather than at room temperature; these measures helped to prevent replantation toxaemia and to preserve muscle function.

Amputation, Surgical↗

Development of highly fluid, concentrated and stable fluorocarbon emulsions for diagnosis and therapy.

A challenging aim in developing injectable fluorocarbon emulsions is to combine good flow characteristics (especially at low shear rates) with the high fluorocarbon concentration required for high oxygen delivery or effective contrast in imaging, long shelf life, and biological acceptability. A good balance of these sometimes conflicting objectives has been achieved with 90% w/v concentrated emulsions of various fluorocarbons, including the radiopaque oxygen carrier perfluorooctylbromide (PFOB, perflubron). The sterile emulsions have viscosities of about 20 cPs at a shear rate of 1 sec-1; the viscosity decreases rapidly with fluorocarbon concentration, and at 60% w/v the viscosity is less than that of human blood. The emulsions are suitable for injection as prepared, and are stable unfrozen for over a year.

Blood Substitutes↗

[Preservation of hepatocytes in UW and HTK solutions with added fluorocarbons].

BACKGROUND: One of the limitations for hepatocyte transplantation is the short survival of isolated hepatocytes. OBJECTIVE: We evaluated the utility of fluorocarbons (PFC) added to University of Wisconsin (UW) and histidine-tryptofane-ketoglutarate (HTK) solutions on hepatocyte preservation. METHOD: Rat hepatocytes were isolated by colagenase digestion technique, with a viability greater than 85% measured by tripan blue exclusion. We suspended 1.2 x 10(8) hepatocytes in 20 mL of: HTK solution, HTK with perfluor-n-octane (HTK + PFC), UW solution, and E. Williams medium as control group (CG). Five samples of each group were stored at 4 degrees C for 40 h. We measured Cell viability, large membrane bleb formation and extracellular LDH at 0, 12, 24 and 36 hours. RESULTS: Cell viability was lower in the UW at 12 h (p < 0.05) and 24 h (p < 0.05) compared to the rest of the study groups; at 36 h we found no differences in cell viability. There were fewer hepatocytes with large membrane blebs in UW + PFC; compared with the remainder of the solutions, but this difference was only reached statistical significance when compared to UW at 24 h (p < 0.05) and at 36 h (p < 0.05). When comparing groups with or without fluorocarbons LDH levels showed no difference at 0, 12, 24, and 36 h. CONCLUSIONS: The present study shows that the addition of fluorocarbons to UW solution diminishes large membrane formation (irreversible damage) and improves cell viability at 12 and 24 h. However, fluorocarbons added to both solutions failed to increase preservation time beyond 24 h.

Adenosine↗

[Current research on oxygen carriers for transfusion: hemoglobin solutions and fluorocarbon emulsions].

Although products currently under study are usually called "artificial blood" or "blood substitutes", it concerns only, for the moment, to achieve preparations able to carry and release oxygen to tissues while allowing also a temporary restoration of "blood" volume. The most advanced scopes are related to hemoglobin solutions and fluorocarbons emulsions. The limitations of free hemoglobin impose to modify it. The reestablishment of a normal, even reduced, affinity for oxygen is obtained by the fixation on hemoglobin of a 2,3-DPG substitute whose most known example is pyridoxal phosphate. The enhancement of vascular retention may be achieved by intramolecular cross-linking, intermolecular polymerization or covalent binding of hemoglobin on macromolecules. The two modifications of hemoglobin must be performed successively et numerous possibilities have been proposed. Bovine and recombinant hemoglobins are also promising. Originally and logically, fluorocarbons are synthetic compounds derived from hydrocarbons by an important or maximal substitution of hydrogen by fluorine. The physical properties of these molecules, impose, for transfusion, their emulsification in an aqueous physiological solution. They need an oxygen enriched atmosphere and their storage in tissues is often extended. At present, the most known emulsion is Fluosol DA, a mixture of perfluorodecalin and perfluorotripropylamine. It allowed to realize numerous researches and the proposal of the multiple possible employment for this category of oxygen carriers. The limitations of Fluosol DA led to fluorocarbons under investigation such as F dimethyl bicyclononanes, F methyladamantane, bis (F-butyl) ethene or F-octylbromide. The new hemoglobin solutions and fluorocarbons emulsions start to meet the requirements of potential users.

Blood Substitutes↗