Effects Of Perfluorocarbon Research Articles

Mini-review: Perfluorocarbons, Oxygen Transport, and Microcirculation in Low Flow States: in Vivo and in Vitro Studies.

The in vivo study of microvascular oxygen transport requires accurate and challenging measurements of several mass transfer parameters. Although recommended, blood flow and oxygenation are typically not measured in many studies where treatments for ischemia are tested. Therefore, the aim of this communication is to briefly review cardinal aspects of oxygen transport, and the effects of perfluorocarbon (PFC) treatment on blood flow and oxygenation based mostly on studies performed in our laboratory. As physiologically relevant events in oxygen transport take place at the microvascular level, we implemented the phosphorescence quenching technique coupled with noninvasive intravital videomicroscopy for quantitative evaluation of these events in vivo. Rodent experimental models and various approaches have been used to induce ischemia, including hemorrhage, micro- and macroembolism, and microvessel occlusion. Measurements show decrease in microvascular blood flow as well as intravascular and tissue oxygen partial pressure (PO2) after these procedures. To minimize or reverse the effects of ischemia and hypoxia, artificial oxygen carriers such as different PFCs were tested. Well-defined endpoints such as blood flow and tissue PO2 were measured because they have significant effect on tissue survival and outcome. In several cases, enhancement of flow and oxygenation could be demonstrated. Similar results were found in vitro: PFC emulsion mixed with blood (from healthy donors and sickle cell disease patients) enhanced oxygen transport. In summary, PFCs may provide beneficial effects in these models by mechanisms at the microvascular level including facilitated diffusion and bubble reabsorption leading to improved blood flow and oxygenation.

The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism.

Acute lung injury (ALI)/ARDS is a critical clinical syndrome with high mortality, and the effective therapeutic methods for the treatment remain limited. Previous studies have indicated that liquid ventilation with perfluorocarbon (PFC) may be advantageous over conventional mechanical ventilation in the treatment of ALI/ARDS. Additionally, PFC inhibits the inflammatory response caused by ALI/ARDS. However, the anti-inflammatory mechanism remains to be completely elucidated. In the present study, the aim was to determine the anti‑inflammatory mechanism of PFC and the association with microRNA (miR). PFC was used to modulate LPS‑induced A549 cells, with the cells divided into four groups: Untreated control group; LPS group, treated with 10 µg/ml LPS; LPS+PFC group, treated with 10 µg/ml LPS and PFC; and PFC group, treated with PFC alone. The intercellular adhesion molecule‑1 (ICAM‑1) mRNA and protein expression levels of each group were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, respectively. A549 cells were transfected with miR‑17‑3p mimics, miR‑17‑3p inhibitors or negative controls to observe the alterations in the anti‑inflammatory effects of PFC. A dual luciferase reporter gene assay was used to determine whether ICAM‑1 is a target gene of miR‑17‑3p. PFC was observed to attenuate the mRNA and protein expression levels of ICAM‑1 in LPS‑induced A549 cells, with no significant effect on the untreated A549 cells. miR‑17‑3p was demonstrated to be regulated by PFC. Transfection with miR‑17‑3p mimics enhanced the anti‑inflammatory effects of PFC, whereas the miR‑17‑3p inhibitor weakened the anti‑inflammatory effects of PFC at early time points. To conclude, the current study indicates that ICAM‑1 was a target gene of miR‑17‑3p, and PFC has anti‑inflammatory effects. Additionally, the present study is the first report, to the best of our knowledge, that PFC is able to attenuate ICAM-1 expression in LPS-induced A549 cells by increasing miR-17-3p expression.

Perfluorocarbon attenuates inflammatory cytokines, oxidative stress and histopathologic changes in paraquat-induced acute lung injury in rats.

The effects of perfluorocarbon (PFC) on paraquat (PQ) induced acute lung injury (ALI) was evaluated among rats. Twenty four Wistar rats were divided into 4 groups: control group injected by saline physiologic 0.9%, PFC group injected by Perfluorocarbon, PQ group injected by PQ and PQ+PFC group injected by PFC one hour after receiving paraquat. Bronchoalveular fluid content, inflammatory cytokines, oxidative and histopathologic changes were measured after 72 h. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1(TGF-β1) in the PQ group were increased compared to either control or PFC groups, but their levels decreased in PQ+PFC group significantly (p<0.05). Also, histopathologic evaluation revealed an increase in malondialdehyde (MDA) and hydroxyproline (HP) in the PQ group but a decrease in PQ+PFC group significantly (p<0.01). PFC emulsion by its anti-inflammatory, anti-oxidative and anti-fibrotic properties can reduce the inflammatory and fibrotic alterations, pulmonary oedema, and pulmonary histopathologic changes created by PQ.

Effects of perfluorocarbon administered at different time points on acute lung injury in rabbits

Objective To evaluate the effects of perfluorocarbon administered at different time points on acute lung injury (ALI) in rabbits. Methods Eighteen New Zealand white rabbits, weighing 1.8-2.4 kg, aged 50-60 days, were randomly divided into 3 groups (n=6 each) using a random number table: ALI group, preventive administration of perfluorocarbon group (group PP), and therapeutic application of perfluorocarbon group (group PA). In group ALI, after the rabbits were mechanically ventilated for 60 min, ALI was induced with oleic acid 0.1 ml/kg injected via the internal jugular vein in three times within 5 min.In group PP, perfluorocarbon was inhaled at 2 ml·kg-1·h-1 for 60 min, and then ALI was induced.In group PA, after the rabbits were mechanically ventilated for 60 min, ALI was induced, and then perfluorocarbon was inhaled at 2 ml·kg-1·h-1 for 60 min.After 30 min stabilization (baseline, T0), at 60 min of ventilation or at 60 min after preventive administration of perfluorocarbon (T1), and at 30, 60, 90 and 150 min after ALI(T2-5), arterial blood samples were collected for blood gas analysis.Oxygenation index was calculated.Broncho-alveolar lavage fluid (BALF) was collected to determine the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) (by ELISA) at T5.The animals were then sacrificed, and lungs were removed for determination of the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B p65 (NF-κB p65) (by Western blot). Wet to dry lung weight ratio (W/D ratio) was calculated. Results Oxygenation index was significantly decreased at T2-5 than at T0 and T1 in the three groups.Compared to group ALI, oxygenation index was significantly increased at T2-5, the concentrations of TNF-α and IL-1β in BALF were decreased, W/D ratio was decreased, and the expression of TLR4 and NF-κB p65 was down-regulated in group PP, and oxygenation index was significantly increased at T5, and no significant change was found in the other parameters in group PA. Conclusion Preventive inhalation of perfluorocarbon 2 ml·kg-1·h-1 can mitigate ALI in rabbits. Key words: Fluorocarbons; Respiratory distress syndrome, adult

The protective effect of perfluorocarbon on the injury of alveolar epithelial cells induced by lipopolysaccharide

Objective To explore the effects of perfluorocarbon (PFC) on the damaged typeⅡ alveolar epithelial cells (AEC Ⅱ) induced by lipopolysaccharide (LPS), and the apoptosis and inflammatory reaction of AEC Ⅱ induced by LPS. Methods Primary AEC Ⅱ was divided into control group according to the random number table method, LPS group, PFC group and PFC+ LPS group. LPS group: LPS (1 μg/ml) was added to cells. PFC group: PFC (20%) was added to cells. PFC+ LPS group: PFC (20%) and LPS (1 μg/ml) were added to cells. The apoptotic rate of AEC Ⅱ was detected by flow cytometry. Morphologic change was observed by electron microscope. Concentrations of interleukin (IL)-6 and IL-10 of supernatant were detected by ELISA. Results Apoptotic rate of AEC Ⅱ remarkably increased in LPS group than in control grouop [(10.89±1.04)% vs (14.29±1.93)%] (P 0.05). Conclusion PFC can protect AEC Ⅱ against the injury induced by LPS. PFC can also release the level of inflammatory response. Key words: Perfluorocarbon; Alveolar epithelial cell; Lipopolysaccharide; Apoptosis; Inflammatory factor

Effects of Perfluorocarbons on surfactant exocytosis and membrane properties in isolated alveolar type II cells

BackgroundPerfluorocarbons (PFC) are used to improve gas exchange in diseased lungs. PFC have been shown to affect various cell types. Thus, effects on alveolar type II (ATII) cells and surfactant metabolism can be expected, data, however, are controversial.ObjectiveThe study was performed to test two hypotheses: (I) the effects of PFC on surfactant exocytosis depend on their respective vapor pressures; (II) different pathways of surfactant exocytosis are affected differently by PFC.MethodsIsolated ATII cells were exposed to two PFC with different vapor pressures and spontaneous surfactant exocytosis was measured. Furthermore, surfactant exocytosis was stimulated by either ATP, PMA or Ionomycin. The effects of PFC on cell morphology, cellular viability, endocytosis, membrane permeability and fluidity were determined.ResultsThe spontaneous exocytosis was reduced by PFC, however, the ATP and PMA stimulated exocytosis was slightly increased by PFC with high vapor pressure. In contrast, Ionomycin-induced exocytosis was decreased by PFC with low vapor pressure. Cellular uptake of FM 1-43 - a marker of membrane integrity - was increased. However, membrane fluidity, endocytosis and viability were not affected by PFC incubation.ConclusionsWe conclude that PFC effects can be explained by modest, unspecific interactions with the plasma membrane rather than by specific interactions with intracellular targets.

Reduction of Postoperative Adhesions by Perfluorocarbons: An Experimental Study in a Rat Model

Peritoneal adhesions are a well-known and frequently occurring postoperative complication. Many published studies have looked into the prophylaxis of adhesions following abdominal surgery, but only few clinically relevant agents have been reported. Most publications refer to adult patients and not to paediatric patient collectives. This experimental study in a rat model compares the effect of perfluorocarbons as adhesion prophylaxis with those of a well-known anti-adhesive agent Adept and with an untreated control group. We hypothesized that PFC might have a double effect: initially it could suppress the accumulation of monocytes and neutrophilic granulocytes, and subsequently it would work as a barrier to prevent contact between the visceral and parietal layers of the peritoneum. After a standardised operation, PFC was injected into the abdominal cavity of rats in the study group. Macroscopically, the PFC group did not fare significantly better, but nevertheless a clear tendency towards fewer adhesions after the application of PFC could be ascertained.

Perfluorocarbon in Microcirculation During Ischemia Reperfusion

The effects of perfluorocarbon (PFC) emulsions administered at a nonhemodiluting dose were studied in the hamster window chamber model to determine the difference in ischemia-reperfusion injury associated with PFC delivery before and after an ischemic episode. Ischemia was induced by compressing the periphery of the window chamber for 1 hour. Vessel diameter, red blood cell velocity, rolling and adherent leukocytes, and functional capillary density (FCD) were assessed by intravital microscopy. The animals received an infusion (10% blood volume) of PFC emulsion or equivalent volumes of saline, before or after ischemia. Two groups were studied in each experimental protocol: A, infusion after ischemia; and B, infusion before ischemia, where a fraction of the infused material stagnated in the ischemic zone during the occlusion time. Measurements were made before induced ischemia and at 0.5, 2, and 24 hours of reperfusion. Animals treated with PFC after ischemia had substantially decreased leukocytes rolling and sticking in postcapillary venules and recovered functional capillary density and blood flow when compared with saline-treated controls. Conversely, administration of PFC before ischemia considerably reduced functional capillary density and increased leukocyte activation after reperfusion. Results indicate that PFC without stagnation within an ischemic zone attenuates postischemic reperfusion injury of striated skin muscle, presumably through the reduction of leukocyte-endothelial cell interactions. Accordingly, PFC effects on ischemia-reperfusion injury are determined mainly by the time of administration relative to the ischemic episodes.

Effect of perfluorocarbons on brain oxygenation and ischemic damage in an acute subdural hematoma model in rats

This study was conducted to determine whether perfluorocarbons (PFCs) improve brain oxygenation and reduce ischemic brain damage in an acute subdural hematoma (SDH) model in rats. Forty adult male Sprague-Dawley rats were allocated to four groups: (1) controls, acute SDH treated with saline and 30% O2; (2) 30-PFC group, acute SDH treated with PFC infusion in 30% O2; (3) 100-O2 group, acute SDH treated with 100% O2; and (4) 100-PFC group, acute SDH treated with PFC plus 100% O2. Ten minutes after the induction of acute SDH, a single dose of PFC was infused and 30% or 100% O2 was administered simultaneously. Four hours later, half of the rats were killed by perfusion for histological study to assess the extent of ischemic brain damage. The other half were used to measure brain tissue oxygen tension (PO2). The volume of ischemic brain damage was 162.4 +/- 7.6 mm3 in controls, 165.3 +/- 11.3 mm3 in the 30-PFC group, 153.4 +/- 17.3 mm3 in the 100-O2 group, and 95.9 +/- 12.8 mm3 in the 100-PFC group (41% reduction compared with controls, p = 0.002). Baseline brain tissue PO2 values were approximately 20 mm Hg, and after induction of acute SDH, PO2 rapidly decreased and remained at 1 to 2 mm Hg. Treatment with either PFC or 100% O2 improved brain tissue PO2, with final values of 5.14 and 7.02 mm Hg, respectively. Infusion of PFC with 100% O2 improved brain tissue PO2 the most, with a final value of 15.16 mm Hg. Data from the current study demonstrated that PFC infusion along with 100% O2 can significantly improve brain oxygenation and reduce ischemic brain damage in acute SDH.

The Effects of Perfluorocarbon on Respiratory Mechanics and Pulmonary Gas Exchange with Methacholine-induced Bronchoconstriction in Cats

Background: Perfluorocarbon (PFC) liquids have high oxygen carrying capacity and relatively low surface tension allowing them to spread evenly through the diseased lung, especially in the case of adult respiratory distress syndrome. But few studies have demonstrated the effects of PFC on a bronchoconstriction model. The aim of this study was to investigate the effects of PFC on pulmonary mechanics and gas exchange in methacholine-induced bronchoconstricted cats using a flow interruption technique. Methods: Twenty male cats were divided into four groups; control group(group C, n = 5), PFC group (group P, PFC 5 ml/kg, n = 5), methacholine group (group M, 25g/kg/min, n = 5), PFC and methacholine group (group MP, n = 5). Respiratory pressure using a flow interruption technique was measured immediately after stabilizing the heart rate and blood pressure 0, ad 15, 30 and 60 min after the start of the intratracheal administration of PFC and/or methacholine infusion, depending on the group. Arterial blood gas analysis was done to compare arterial partial oxygen pressure among the groups at the time of measuring the pressure values. The pressure data was transferred to a personal computer and analyzed using ANADAT software program. Respiratory, airway and tissue viscoelastic pressure were calculated, Statistical analysis was done by ANOVA and statistical significance was defined as P

Effect of perfluorocarbon (perfluorooctyl bromide) vapor on tidal volume measurement during partial liquid ventilation.

To compare measured tidal volumes with and without perfluorocarbon (perfluorooctyl bromide) vapor, by using tidal volumes in the range suitable for neonates ventilated with partial liquid ventilation. We also aimed to determine the correction factor needed to calculate tidal volumes measured in the presence of perfluorooctyl bromide vapor. Prospective, experimental study. Neonatal research laboratory. Reproducible tidal volumes from 5 to 30 mL were produced with a rodent ventilator and drawn from humidifier chambers immersed in a water bath at 37 degrees C. Control tidal volumes were drawn from a chamber containing oxygen and water vapor, and the perfluorocarbon tidal volumes were drawn from a chamber containing oxygen, water vapor, and perfluorooctyl bromide vapor. Tidal volumes were measured by a VenTrak respiratory mechanics monitor with a neonatal flow sensor and a Dräger pneumotachometer attached to a Dräger neonatal ventilator. All tidal volumes measured with perfluorooctyl bromide vapor were increased compared with control. The VenTrak-measured tidal volumes increased by 1.8% to 3.5% (an overall increase of 2.2%). The increase was greater with the Dräger hot-wire anemometer: from 2.4% to 6.1% (an overall increase of 5.9%). Regression equations for mean control tidal volumes (response, Y) vs. mean perfluorooctyl bromide tidal volumes (predictor, X) are as follows: for the VenTrak, Y = -0.026 + (0.978 x X), r =.9999, p <.0001; and for the Dräger, Y = 0.251 + (0.944 x X), r =.9996, p <.0001. The presence of perfluorooctyl bromide vapor in the gas flowing through pneumotachometers gives falsely high tidal volume measurements. An estimate of the true tidal volume allowing for the presence of perfluorooctyl bromide vapor can be made from regression equations. Any calculation of lung mechanics must take into account the effect of perfluorooctyl bromide vapor on the measurement of tidal volume.

INTRATRACHEAL INSTILLATION OF PERFLUOROCARBON RESCUED MICE WITH PRIMARY PULMONARY HYPOPLASIA

The aim of this study was to investigate the effect of perfluorocarbon on the respiratory status of newborn mice with pulmonary hypoplasia without diaphragmatic defects, following intrauterine exposure to nitrofen. Three groups of newborn mice were compared: pups exposed to nitrofen antenatally without (group A) or with (group B) perfluorocarbon treatment and pups not exposed to nitrofen as a control (group C). Respiratory evaluation was performed by scoring, pressure-volume analysis, and histological examination. At 40 minutes after birth, the survival rates in groups A, B, and C were 51%, 94%, and 95%, respectively. The clinical scores of group B mice at 40 minutes were significantly better than those of group A mice in which pulmonary hypoplasia was induced. In group B, the hysteresis ratio was significantly higher than that in group A, and lung histology showed a significant increase in airspace. An immunohistochemical examination showed that perfluorocarbon did not alter the expression of mature surfactant protein B and surfactant proprotein C. This study demonstrated that treatment with perfluorocarbon was useful in stabilizing critically ill mice with primary pulmonary hypoplasia during the early phase of therapy.

Effects of perfluorocarbons and perfluorocarbons/surfactant emulsions on growth and viability of group B streptococci and Escherichia coli.

Partial liquid ventilation with perfluorocarbons (PFC) might be used as a new ventilatory strategy to treat respiratory insufficiency in congenital pneumonia. The present study investigates for the first time effects of PFC on growth and viability of group B streptococci (GBS) and Escherichia coli, bacteria frequently causing congenital pneumonia. Prospective, in vitro study. Research laboratory in a university. Group B streptococci 090 Ia HD Colindale and E. coli K12, JM 101. E. coli (10(7)/mL) were grown in the absence or presence of different PFC (RM 101, PF 5080, FO 6167) for up to 6 hrs. To study bacterial viability, GBS (5 x 10(7)/mL) were incubated in saline with or without different PFC, PFC/surfactant emulsions, or surfactant (Curosurf) for up to 5 hrs. Every 2 hrs, the colony forming units were determined by plating different dilutions of bacteria on agar. RM 101 or PF 5080 alone and in emulsions with surfactant had no effect on viability of GBS or growth of E. coli. For FO 6167, a previously described toxicity was found, even if 1 mL of GBS suspension was incubated with only 100 microL of FO 6167, verifying the experimental design that guarantees a PFC bacteria contact. The toxic effects were almost prevented by forming a PFC-in-surfactant emulsion but not by preincubation of GBS with surfactant and subsequent FO 6167 exposure. RM 101 and PF 5080 did not influence bacterial growth in vitro; direct effects on bacterial proliferation during partial liquid ventilation in congenital pneumonia seem, therefore, unlikely. Interestingly, we found that the known toxic effects of FO 6167 can be prevented by covering PFC with a surfactant film. Surfactant reduced the cytotoxic effects of FO 6167, probably by preventing a direct contact between FO 6167 and the bacterial cell wall.

Effects of Perfluorocarbon in Spontaneously Breathing Mice • 1660

Perfluorooctylbromide (PFOB) is a perfluorocarbon that has been shown to improve lung function in infants and animals with respiratory distress secondary to surfactant deficiency. We recently demonstrated that although PFOB treatment improved lung function and survival in surfactant protein-B(SP-B) deficient newborn mice, it also adversely affected lung histology. To more closely examine the effects of PFOB on the lung, we instilled PFOB into the lungs of Balb/c mice (n=137, anesthetized with methoxyflurane) in amounts equal to the estimated functional residual capacity. The mice recovered within 1-5 min and were examined 3h-7d after treatment. By 3h, histologic examination revealed evidence of interstitial swelling in perivascular areas and alveolar damage consisting of septal swelling with abundant cells and exudate in the alveoli. Total cells recovered in bronchoalveolar lavage fluid (BAL; sum of 5×1mL washes with cold saline obtained immediately after euthanasia) increased from 2.33±0.70×105 at baseline to 3.85±0.74×106 and 1.42±0.22×107 at 3 and 24 h after treatment, respectively (p 90% at 3 h) and neutrophils (>40% at 24 h). Lung permeability, assessed by measuring the amount of125 I-albumin injected i.p. that gained access to the lavage fluid after 2 h, increased significantly to 3x baseline at 3h and to 4.4x baseline at 5h following PFOB treatment (p<0.04). Although SP-B concentration remained unchanged in BAL fluid, protein concentration increased significantly(p<0.03) so that the ratio of SP-B to protein concentration decreased significantly (p<0.05) following PFOB treatment. Preliminary measurements of static lung compliance indicate that PFOB treatment alters lung compliance. These studies in mice demonstrate that early effects of PFOB treatment may alter lung structure, integrity and SP-B function in a manner that can seriously affect lung function.

Morphological changes in red cells exposed to perfluorodecalin and oxygenation

The hemoprotective effect of perfluorocarbons was studied by examining the surface architectonics of red cells during exposure of the blood to perfluorodecalin and contact oxygenation. Scanning electron microscopy revealed an, appeciable increase in the percentage of damaged erythrocytes directly exposed to oxygen in a contact oxygenator. Interaction between blood and perfluorodecalin not only does not impair the morphology of the blood, but also prevents untoward effects of subsequent contact oxygenation. Fluorocarbon treatment of the blood gives rise to a number (up to 17–18%) of special cells, which morphologically represent somewhat altered normocytes with increased resistance, this reflecting a specific reaction of the blood to perfluorodecalin.

Effect of perfluorochemical emulsion on lipoproteins of plasma blood.

The effect of perfluorocarbons (PFC, Perfluorodecalin/Fogalin) on the lipoprotein level in plasma was studied. The PFC emulsion (FCE) was injected i.v. at a dose of 6 g PFC per kg of body weight into male Wistar rats weighing 250-280 g. The lipoproteins were separated by preparative centrifugation. It was found that PFCs influence the metabolism of lipoproteins. The greatest depletion of cholesterol level occurs in the HDL fraction of lipoproteins 3 and 24 hrs after injection. There is no relationship between the level of cholesterol in plasma and cholesterol lipoproteins. The content in lipoproteins, however, amounts to half the level of the cholesterol of plasma 72 hrs after injection. Based on these facts it is possible to conclude that when PFCs leave the cells of organs, they are carmed in the blood stream as a complex which contains at least PFCs, cholesterol and triglycerides.

Effect of perfluorocarbons on the ultraviolet absorption and fluorescence characteristics of some saturated hydrocarbon liquids

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of perfluorocarbons on the ultraviolet absorption and fluorescence characteristics of some saturated hydrocarbon liquidsHae Tak Choi and Sanford LipskyCite this: J. Phys. Chem. 1981, 85, 26, 4089–4099Publication Date (Print):December 1, 1981Publication History Published online1 May 2002Published inissue 1 December 1981https://doi.org/10.1021/j150626a028RIGHTS & PERMISSIONSArticle Views108Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts