Perfluorocarbon Emulsions Research Articles

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.

Recent Advances in 19Fluorine Magnetic Resonance Imaging with Perfluorocarbon Emulsions.

The research roots of 19fluorine (19F) magnetic resonance imaging (MRI) date back over 35 years. Over that time span, 1H imaging flourished and was adopted worldwide with an endless array of applications and imaging approaches, making magnetic resonance an indispensable pillar of biomedical diagnostic imaging. For many years during this timeframe, 19F imaging research continued at a slow pace as the various attributes of the technique were explored. However, over the last decade and particularly the last several years, the pace and clinical relevance of 19F imaging has exploded. In part, this is due to advances in MRI instrumentation, 19F/1H coil designs, and ultrafast pulse sequence development for both preclinical and clinical scanners. These achievements, coupled with interest in the molecular imaging of anatomy and physiology, and combined with a cadre of innovative agents, have brought the concept of 19F into early clinical evaluation. In this review, we attempt to provide a slice of this rich history of research and development, with a particular focus on liquid perfluorocarbon compound-based agents.

Nanoparticles of perfluorocarbon emulsion contribute to the reduction of methemoglobin to oxyhemoglobin

Here we show that methemoglobin is converted to oxyhemoglobin in the presence of perfluorocarbon (PFС) emulsion. Methemoglobin in blood at the level of above 30% can cause severe complications and lethal outcome. Some pharm chemicals in blood in vivo and in vitro can lead to oxidation of iron, Fe2+→Fe3+, and to increased level of methemoglobin. The oxidized heme is not able to carry oxygen, hypoxia arises and irreversible changes are developing in vital organs. We added NaNO2 solution in different concentrations to blood in vitro in order to yield methemoglobin. Then the suspension of PFC nanoparticles was added. As methemoglobin interacted with PFC nanoparticles the optical density of peaks typical for oxyhemoglobin increased and spectral peak of methemoglobin decreased. The greater the concentration of PFC and the more was the incubation time, the more efficient was the process of reduction of methemoglobin to oxyhemoglobin. We proved experimentally that with an initial concentration of methemoglobin ​in average 95% the addition of nanoparticles of PFC decreases its concentration to 9% ​in average. At the same time the concentration of oxyhemoglobin increased in average from 5% to 81%.

Design and Characterization of Fibrin-Based Acoustically Responsive Scaffolds for Tissue Engineering Applications

Hydrogel scaffolds are used in tissue engineering as a delivery vehicle for regenerative growth factors. Spatiotemporal patterns of growth factor signaling are critical for tissue regeneration, yet most scaffolds afford limited control of growth factor release, especially after implantation. We previously found that acoustic droplet vaporization can control growth factor release from a fibrin scaffold doped with a perfluorocarbon emulsion. This study investigates properties of the acoustically responsive scaffold (ARS) critical for further translation. At 2.5 MHz, acoustic droplet vaporization and inertial cavitation thresholds ranged from 1.5 to 3.0 MPa and from 2.0 to 7.0 MPa peak rarefactional pressure, respectively, for ARSs of varying composition. Viability of C3H/10T1/2 cells, encapsulated in the ARS, did not decrease significantly for pressures below 4 MPa. ARSs with perfluorohexane emulsions displayed higher stability versus those with perfluoropentane emulsions, while surrogate payload release was minimal without ultrasound. These results enable the selection of ARS compositions and acoustic parameters needed for optimized spatiotemporally controlled release.

Toward monodisperse ultrasound-triggered phase-shift emulsions using differential centrifugation

Acoustic droplet vaporization (ADV) is a process that enables the in situ production of microbubbles from an injected perfluorocarbon emulsion and it has been investigated for imaging and therapeutic applications. High-speed mechanical shaking rapidly produces a polydisperse emulsion (~1010 droplets/mL) with droplets ranging from less than 400 nm to greater than 15 μm. The ADV pressure amplitude threshold is higher and fraction of transitioned droplets lower for droplets smaller than approximately 2 μm in diameter. Droplets greater than approximately 8 μm in diameter are not suitable for systemic administration. Therefore, high-speed mechanical shaking produces many droplets of limited utility. Differential centrifugation has been used as a size isolation technique for polydisperse ultrasound contrast agents. By applying a similar technique to a perfluorocarbon emulsion, the volume-weighted fraction of droplets between 2 and 5 μm was increased from 29±2% to 93±3%. The transition efficiency of the droplets between 2and 5 μm was the same regardless of whether a polydisperse or monodisperse distribution was insonfied with 2 MHz ultrasound. The ADV pressure threshold of differentially centrifuged droplets was similar to non-centrifuged droplets. [Supported in part by NIH grant KL2 T78.]

Phase Change Nanoemulsions for Cancer Therapy and Imaging

Much of the biological therapeutics currently available struggle to function as effective drug delivery vehicles due in part to their poor stability, solubility, and permeability across barriers such as the tight junctions between endothelial cells in tumor vasculature. Given this understanding, there is currently a significant interest in designing nanocarriers (< 100 nm in diameter) which are able to increase the bioavailability of drugs. In particular, much attention has been focused on nanoemulsions whose liposome-like structure protects drugs against physico-chemical and enzymatic degradation and charged surface favors drug adsorption. One novel class of nanoemulsions called perfluorocarbon (PFC) emulsions are of particular interest because they can be used both for delivering drugs and imaging tumors. In this work we show that nanoemulsions with a PFC core and Zonyl FSP surfactant shell can be produced using an oil-in-water technique via sonication. This technique is successful in producing PFC emulsions that are on average 50 nm in diameter with long-term stability at physiological conditions, as determined by Electron Microscopy, Fluorescence Correlation Spectroscopy and Dynamic Light Scattering. Using laser excitation, these nanoemulsions can vaporize into microbubbles in the presence of silica coated gold nanoparticles for efficient drug release and imaging using high contrast imaging modalities such as photoacoustic microscopy. Taken together, the size and stability of these PFC nanodroplets make them cost effective drug delivery vehicles suitable for efficient internalization by cancer cell lines.

Effects of Perfluorocarbon Dodecafluoropentane (NVX-108) on Cerebral Microvasculature in the Healthy Rat

NVX-108, a dodecafluoropentane-based perfluorocarbon (PFC) emulsion, has therapeutic potential as an oxygen- carrying fluid for emergency medical treatment for traumatic brain injury (TBI) and hemorrhagic shock. Potential cerebral vasoactive properties were assessed by directly measuring pial arteriolar vessel diameters before and after a 30 minute intravenous (IV) infusion of 1.0 ml/kg (high dose [H]) or 0.25 ml/kg (low dose [L]) NVX-108 compared to 2.0 ml/kg Saline (control) in healthy anesthetized rats (N = 6/group). Results showed that post-infusion vessel diameters for small (< 50 µm) and medium (50-100 µm)-sized pial arterioles were significantly (p < 0.05) narrower after only the NVX- 108 H infusion although this vasoconstriction was not statistically significant when analyzed as a percentage change in these vessels. Pial arteriolar vessel diameters were not significantly different for mean value or percentage change after either NVX-108 L or Saline infusions. There were no significant post-infusion changes from baseline in systolic, mean or diastolic blood pressures after any of the treatments although post-infusion blood pressure was statistically higher in the NVX-108 L group compared to NVX-108 H and Saline groups. Arterial blood gases, methemoglob in and lactate were not different from baseline or among groups. No adverse events were observed at either dose of NVX-108. In conclusion, neither 0.25 nor 1.0 ml/kg NVX-108 caused vasoconstriction in cerebral pial arterioles of healthy rats nor resulted in blood pressure changes; the compound should be considered for further investigation for TBI therapy.

Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance.

Neurotrophic effects of perfluorocarbon emulsion gel: a pilot study

BackgroundPositive neurotrophic effects of hyperbaric oxygen treatment may be more easily achieved by applying a Perflourocarbon (PFC) emulsion gel to the repair site. PFCs are halogen substituted carbon oils with unique oxygen transport potentials that are capable of increasing oxygen availability in local tissues. The purpose of this study was to determine if the application of a PFC emulsion to a repaired nerve would improve recovery.Materials and methodsThe left tibial nerve of 21 immature female Sprague-Dawley rats was transected, immediately repaired, and then circumferentially coated with PFC gel (Group A, n = 7), PFC-less gel (Group B, n = 7), or nothing (suture only, Group C, n = 7). At eight weeks post surgery, electrophysiological testing and histological and morphological analysis was performed.ResultsNo statistically significant differences between experimental groups were found for muscle size and weight, axon counts, or nerve conduction velocity. Group A had a significantly smaller G-ratio than Groups B and C (p < .0001).ConclusionOverall results do not indicate a functional benefit associated with application of a PFC emulsion gel to rodent tibial nerve repairs. A positive effect on myelination was seen.

Internal deoxygenation of tubular photobioreactor for mass production of microalgae by perfluorocarbon emulsions

BACKGROUND With the increasing demand for microalgae it is clear that new industrial culturing techniques are needed. Current microalgae growth is done either in open or closed systems. In various situations, it has been reported that closed systems offer many advantages over open systems including lower contamination and better control over operating parameters. However, in industrial scale-up of closed tubular photobioreactors, hypercritical oxygen concentration is one of the dominating detrimental factors limiting the mass culture of microalgae in tubular systems. However, published accounts on alleviating oxygen stress imposed on large-scale tubular photobioreactors are scarce. RESULTS Results from this work showed that perfluorocarbon (PFC) emulsions, acting as gas-carrier vehicles, increased algal photosynthesis and biomass at least 4-fold in a closed tubular photobioreactor by decreasing dissolved oxygen concentration from 47% (generated in the photobioreactor without using PFC emulsions) to 4% after 9 days of culture. CONCLUSION In order to tackle the problem of high concentrations of dissolved oxygen strongly inhibiting microalgal biomass production, an innovative methodology has been developed which involves gradually supplying carbon dioxide and removing the accumulated oxygen through the use of PFC emulsions. © 2014 Society of Chemical Industry

The assessment of morphological state of pancreas in experimental pancreonecrosis treated with perfluorocarbon emulsions

The assessment of morphological state of pancreas in experimental pancreonecrosis treated with perfluorocarbon emulsions

Perfluorocarbons enhance oxygen transport in alginate‐based hydrogels

A major limitation of current soft biomaterials for tissue engineering and cell encapsulation is inadequate transport of oxygen to cells and tissues. Oxygen transport is a challenge in nearly all aqueous hydrogel biomaterials. Here, we report the effective diffusivity of oxygen in alginate‐based hydrogels containing stable perfluorocarbon (PFC) emulsions. Incorporation of 7% perfluorooctyl bromide into the alginate gels was found to increase oxygen permeability by a factor of three. Our work also demonstrates that the increase in oxygen transport is largely due to improved oxygen solubility in PFC‐containing gels. Although promising, this improved oxygen transport comes with a trade‐off in terms of mechanical robustness. This must be carefully considered in future development of PFC‐containing hydrogels for biomedical devices. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Therapeutic Effect of Intravenous Infusion of Perfluorocarbon Emulsion on LPS-Induced Acute Lung Injury in Rats

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC), a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide). In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS) induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group), 18 rats were treated with LPS by intratracheal instillation (LPS group) and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group). The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2) and lung wet-dry weight ratio (W/D) of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN) induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice.

Relaxometric studies of gadolinium‐functionalized perfluorocarbon nanoparticles for MR imaging

Fluorine MRI ((19) F MRI) is receiving an increasing attention as a viable alternative to proton-based MRI ((1) H MRI) for dedicated application in molecular imaging. The (19) F nucleus has a high gyromagnetic ratio, a 100% natural abundance and is furthermore hardly present in human tissues allowing for hot spot MR imaging. The applicability of (19) F MRI as a molecular and cellular imaging technique has been exploited, ranging from cell tracking to detection and imaging of tumors in preclinical studies. In addition to applications, developing new contrast materials with improved relaxation properties has also been a core research topic in the field, since the inherently low longitudinal relaxation rates of perfluorocarbon compounds result in relatively low imaging efficiency. Borrowed from (1) H MRI, the incorporation of lanthanides, specifically Gd(III) complexes, as signal modulating ingredients in the nanoparticle formulation has emerged as a promising approach to improvement of the fluorine signal. Three different perfluorocarbon emulsions were investigated at five different magnetic field strengths. Perfluoro-15-crown-5-ether was used as the core material and Gd(III)DOTA-DSPE, Gd(III)DOTA-C6-DSPE and Gd(III)DTPA-BSA as the relaxation altering components. While Gd(III)DOTA-DSPE and Gd(III)DOTA-C6-DSPE were favorable constructs for (1) H NMR, Gd(III)DTPA-BSA showed the strongest increase in (19F) R(1). These results show the potential of the use of paramagnetic lipids to increase (19F) R(1) at clinical field strengths (1.5-3 T). At higher field strengths (6.3-14 T), gadolinium does not lead to an increase in (19F) R(1) compared with emulsions without gadolinium, but leads to an significant increase in (19F) R(2). Our data therefore suggest that the most favorable situation for fluorine measurements is at high magnetic fields without the inclusion of gadolinium constructs.

Acceleration of ultrasound thermal therapy by patterned acoustic droplet vaporization

One application of acoustic droplet vaporization (ADV), a method of converting biocompatible microdroplets into microbubbles, is to enhance locally high intensity focused ultrasound (HIFU) therapy. Two objectives are pursued here: (1) the controlled creation of a bubble trench prior to HIFU using ADV and (2) use of the trench for increasing ablation volumes, lowering acoustic powers, and decreasing therapy duration. Thermally responsive phantoms were made with perfluorocarbon emulsion. Compound lesions were formed in a laboratory setting and a clinical magnetic resonance imaging (MRI)-guided HIFU system. Linear and spiral patterned compound lesions were generated in trenches. A larger fraction of the HIFU beam is contained to increase the generation of heat. Using the laboratory system, a 90 mm linear length spiral trench was formed in 30 s with mechanical beam steering. Comparatively, the clinical HIFU system formed a 19.9 mm linear length spiral trench in approximately 1 s with electronic beam steering. Lesions were imaged optically and with MRI. A uniform thermal ablation volume of 3.25 mL was achieved in 55.4 s (4-times faster than standard clinical HIFU and 14-times larger volume versus sum of individual lesions). Single lesions showed a 400% volume increase.

Bioluminescence and 19 F Magnetic Resonance Imaging Visualize the Efficacy of Lysostaphin Alone and in Combination with Oxacillin against Staphylococcus aureus in Murine Thigh and Catheter-Associated Infection Models

Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been evaluated. Lysostaphin exerts high levels of activity against antibiotic-resistant strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). The therapeutic value of lysostaphin has been analyzed in two different clinically relevant in vivo models, a catheter-associated infection model and a thigh infection model. We infected mice with luciferase-expressing S. aureus Xen 29, and the efficacies of lysostaphin, vancomycin, oxacillin, and combined lysostaphin-oxacillin were investigated by determining numbers of CFU, detecting bioluminescent signals, and measuring the accumulation of perfluorocarbon emulsion at the site of infection by (19)F magnetic resonance imaging. Lysostaphin treatment significantly reduced the bacterial burden in infected thigh muscles and, after systemic spreading from the catheter, in inner organs. The efficiency of lysostaphin treatment was even more pronounced in combinatorial therapy with oxacillin. These results suggest that recombinant lysostaphin may have potential as an anti-S. aureus drug worthy of further clinical development. In addition, both imaging technologies demonstrated efficacy patterns similar to that of CFU determination, although they proved to be less sensitive. Nonetheless, they served as powerful tools to provide additional information about the course and gravity of infection in a noninvasive manner, possibly allowing a reduction in the number of animals needed for research evaluation of new antibiotics in future studies.

Treatment of micro air bubbles in rat adipose tissue at 25 kPa altitude exposures with perfluorocarbon emulsions and nitric oxide

Perfluorocarbon emulsions (PFC) and nitric oxide (NO) releasing agents have on experimental basis demonstrated therapeutic properties in treating and preventing the formation of venous gas embolism as well as increased survival rate during decompression sickness from diving. The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i.e., oxygen in particular) and water vapor contribute to bubble growth and stabilization during altitude exposures. Accordingly, we hypothesize that the administration of PFC and NO donors upon hypobaric pressure exposures either (1) enhance the bubble disappearance rate through faster desaturation of nitrogen, or in contrast (2) promote bubble growth and stabilization through an increased oxygen supply. In anesthetized rats, micro air bubbles (containing 79% nitrogen) of 4-500 nl were injected into exposed abdominal adipose tissue. Rats were decompressed in 36 min to 25 kPa (~10,376 m above sea level) and bubbles studied for 210 min during continued oxygen breathing (FIO2 = 1). Rats were administered PFC, NO, or combined PFC and NO. In all groups, most bubbles grew transiently, followed by a stabilization phase. There were no differences in the overall bubble growth or decay between groups or when compared with previous data during oxygen breathing alone at 25 kPa. During extreme altitude exposures, the contribution of metabolic gases to bubble growth compromises the therapeutic effects of PFC and NO, but PFC and NO do not induce additional bubble growth.

Effects of perfluorocarbon emulsions on microvascular blood flow and oxygen transport in a model of severe arterial gas embolism

BackgroundArterial gas embolism (AGE) is a clinical problem that occurs directly in cardiopulmonary bypass machines in open-heart surgeries, or indirectly (through cardiac or pulmonary right to left shunts) in dive accidents, resulting in serious morbidity and even death. Perfluorocarbon (PFC) emulsions have been used for the treatment of AGE in an animal model. We hypothesized that PFC emulsions enhance microvascular blood flow, speed bubble resolution, and oxygenation in AGE compared with saline in a model of cremaster muscle from anesthetized rats. Materials and methodsAGE was induced by direct air injection into the femoral artery ipsilateral to the studied cremaster muscle. Microhemodynamics, microvascular, and tissue oxygenation were determined before and after treatment with two different commercial PFC emulsions (C10F20, Oxycyte; Oxygen Biotherapeutics, Inc and C10F18, PHER-O2; Sanguine Corporation, Inc) compared with saline in real time using brightfield and phosphorescence microscopy. ResultsBlood pressure and heart rate remained unchanged. Systemic PO2, oxygen (O2) content, and glucose were higher in PFC groups, whereas hematocrit dropped in all groups. Arteriolar blood flow went up 85% and 80% of baseline after C10F20 and C10F18 treatments, respectively, versus 11% after saline treatment. Arteriolar and tissue PO2, and O2 delivery were higher in PFC groups compared with the control group. There was an increase in arteriolar blood flow, reduction in diffusional resistance of O2 in the plasma, and improved tissue oxygenation. ConclusionsAdministration of PFC emulsions in AGE is superior to saline primarily because of surfactant properties along with air bubble reabsorption.

Protective effect of perfluorocarbon emulsions on rat donor lung

Objective To evaluate the protective effect of perfluorocarbon emulsions (FCE) on donor lung of rats during storage.Methods Twenty-four healthy male Sprague-Dawley rats,weighing 350-400 g,were equally and randomly divided into 2 groups using a random number table:University of Wisconsin (UW) solution group (UW group) and FCE group (FCE group).After the model of lung perfusion was established according to the method described by Fischer et al,the lung and heart were removed and perfused with 4 ℃ UW or FCE preservation solutions.The lung was taken out when stored for 6 h for determination of SOD activity (by WST assay),malondialdehyde (MDA) content (by TBA assay),and activity of myeloperoxidase (MPO) and content of interleukin1 β (IL-1β),IL-6,tumor necrosis factor-apha (TNF-α) (using ELISA) in lung tissues and for microscopic examination of pathologic changes.Results MPO activity was significantly lower in UW group than in FCE group (P ＜0.05).There were no significant differences in the SOD activity and content of MDA,IL-1β,IL-6,TNF-α between the two groups (P ＞ 0.05).Conclusion FCE can reduce the neutrophil infiltration in lung tissues,indicating that FCE is more superior to UW solution in reduction of injury to the donor lung of rats. Key words: Fluorocarbons ; Emulsifying agents; Lung transplantation; Cytoprotection

Transport of nitric oxide by perfluorocarbon emulsion

Perfluorocarbon (PFC) emulsions can transport and release various gases based on concentration gradients. The objective of this study was to determine the possibility of carrying and delivering exogenous nitric oxide (NO) into the circulation by simply loading PFC emulsion with NO prior infusion. PFC was equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure. Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood chemistry, and systemic and microvascular hemodynamic response were measured. Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular vasodilation and increased capillary perfusion; although these changes lasted less than 30 min post infusion. On the other hand, infusion of PFC (without NO) produced vasoconstriction; however, the vasoconstriction was followed by vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15 min after infusion of NO preloaded PFC compared with PFC, 60 min after infusion nitrite and nitrate were not different, and 90 min after infusion plasma S-nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in acute vascular relaxation, where as infusion of PFC (without NO) produced vasoconstriction, potentially due to NO sequestration by the PFC micelles. The late effects of PFC infusion are due to NO redistribution and plasma S-nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma vasoactive NO forms availability and improve microcirculatory function and promote increased blood flow.