Perfluorochemical Liquid Research Articles

Perfluorochemical-facilitated plasminogen activator delivery to the airways: A novel treatment for inhalational smoke-induced acute lung injury.

BackgroundEffective clinical management of airway clot and fibrinous cast formation of severe inhalational smoke‐induced acute lung injury (ISALI) is lacking. Aerosolized delivery of tissue plasminogen activator (tPA) is confounded by airway bleeding; single‐chain urokinase plasminogen activator (scuPA) moderated this adverse effect and supported transient improvement in gas exchange and lung mechanics. However, neither aerosolized plasminogen activator (PA) yielded durable improvements in physiologic responses or reduction in cast burden. Here, we hypothesized that perfluorochemical (PFC) liquids would facilitate PA distribution and sustain improvements in physiologic outcomes in ISALI.MethodsSpontaneously breathing adult sheep (n = 36) received anesthesia and analgesia and were instrumented, exposed to cotton smoke inhalation, and supported by mechanical ventilation for 48 h. Groups (n = 6/group) were studied without supplemental treatment, or, starting 4 h post injury, they received intratracheal low volume (8 mL) PFC liquid alone or a dose range of tPA/PFC or scuPA/PFC suspensions (4 or 8 mg in 8 mL PFC) every 8 h. Outcomes were evaluated by sequential measurements of cardiopulmonary parameters, lung histomorphology, and biochemical analyses of bronchoalveolar lavage fluid.ResultsDose‐response and PA‐type comparisons of outcomes demonstrated sustained superiority with low‐volume PFC suspensions of scuPA over tPA or PFC alone, favoring the highest dose of scuPA/PFC suspension over lower doses, without airway bleeding.ConclusionsWe propose that this improved profile over previously reported aerosolized delivery is likely related to improved dose distribution. Sustained salutary responses to scuPA/PFC suspension delivery in this translational model are encouraging and support the possibility that the observed outcomes could be of clinical importance.

Liquid ventilation.

Human have lungs to breathe air and they have no gills to breath liquids like fish. When the surface tension at the air-liquid interface of the lung increases as in acute lung injury, scientists started to think about filling the lung with fluid instead of air to reduce the surface tension and facilitate ventilation. Liquid ventilation (LV) is a technique of mechanical ventilation in which the lungs are insufflated with an oxygenated perfluorochemical liquid rather than an oxygen-containing gas mixture. The use of perfluorochemicals, rather than nitrogen as the inert carrier of oxygen and carbon dioxide offers a number of advantages for the treatment of acute lung injury. In addition, there are non-respiratory applications with expanding potential including pulmonary drug delivery and radiographic imaging. It is well-known that respiratory diseases are one of the most common causes of morbidity and mortality in intensive care unit. During the past few years several new modalities of treatment have been introduced. One of them and probably the most fascinating, is of LV. Partial LV, on which much of the existing research has concentrated, requires partial filling of lungs with perfluorocarbons (PFC's) and ventilation with gas tidal volumes using conventional mechanical ventilators. Various physico-chemical properties of PFC's make them the ideal media. It results in a dramatic improvement in lung compliance and oxygenation and decline in mean airway pressure and oxygen requirements. No long-term side-effect reported.

Inhalation of Nebulized Perfluorochemical Enhances Recombinant Adenovirus and Adeno-Associated Virus-Mediated Gene Expression in Lung Epithelium

Use of perfluorochemical liquids during intratracheal vector administration enhances recombinant adenovirus and adeno-associated virus (AAV)-mediated lung epithelial gene expression. We hypothesized that inhalation of nebulized perfluorochemical vapor would also enhance epithelial gene expression after subsequent intratracheal vector administration. Freely breathing adult C57BL/6 mice were exposed for selected times to nebulized perflubron or sterile saline in a sealed Plexiglas chamber. Recombinant adenoviral vector was administered by transtracheal puncture at selected times afterward and mice were killed 3 days after vector administration to assess transgene expression. Mice tolerated the nebulized perflubron without obvious ill effects. Vector administration 6 hr after nebulized perflubron exposure resulted in an average 540% increase in gene expression in airway and alveolar epithelium, compared with that with vector alone or saline plus vector control (p<0.05). However, vector administration 1 hr, 1 day, or 3 days after perflubron exposure was not different from either nebulized saline with vector or vector alone and a 60-min exposure to nebulized perflubron is required. In parallel pilot studies in macaques, inhalation of nebulized perflubron enhanced recombinant AAV2/5 vector expression throughout the lung. Serial chest radiographs, bronchoalveolar lavages, and results of complete blood counts and serum biochemistries demonstrated no obvious adverse effects of nebulized perflubron. Further, one macaque receiving nebulized perflubron only was monitored for 1 year with no obvious adverse effects of exposure. These results demonstrate that inhalation of nebulized perflubron, a simple, clinically more feasible technique than intratracheal administration of liquid perflubron, safely enhances lung gene expression.

Perfluorodecalin lavage of a longstanding lung atelectasis in a child with spinal muscle atrophy

Persistent lung atelectasis is difficult to treat and perfluorochemical (PFC) liquid may be an option for bronchioalveolar lavage (BAL). A 4-year-old girl with spinal muscle atrophy was admitted in respiratory failure. On admission, the X-ray confirmed the persistence of total right-sided lung atelectasis, which had been present for 14 months. She was endotracheally intubated and ventilated from the day of admission. BAL with normal saline was performed twice without improvement. Following failed extubation and being dependent on continuous respiratory support, a trial of BAL using PFC liquid (Perfluorodecalin HP) was carried out. The PFC was delivered through the endotracheal tube on three consecutive days. A loading dose of 3 ml/kg was administered, followed by a varying dose in order to more effectively lavage the lungs. She tolerated the procedure well the first 2 days, although there were no clinical signs of improvement in the atelectasis. Intentionally, higher inflation pressures were applied after PFC instillation on day 3. Chest X-ray then showed hazy infiltrates on her left lung and she required more ventilatory support. However, lung infiltrates cleared over the next 3 days. A tracheotomy was done 6 days after the last PFC instillation. She had a slow recovery and was successfully decanulated. Clinical improvement of lung function was seen including less need of BiPAP and oxygen. A chest CT scan showed then functional lung tissue appearing in the previous total atelectatic right lung. Lavage with PFC can safely be performed with a therapeutic effect in a child with unilateral total lung atelectasis.

Efficacy of intratracheal instillation of a meropenem/perfluorochemical suspension in acute lung injury

Perfluorochemical (PFC) is theoretically a good vehicle for delivering biological agents to the lungs. This study was designed to investigate the efficacy of intratracheal (IT) instillation of meropenem using PFC liquid as a vehicle in a piglet model of acute lung injury (ALI). Eighteen piglets were injured with lung lavages to induce ALI, and randomly assigned to intravenous (IV) infusion or IT instillation groups, the latter using either PFC or normal saline (NS) as a delivery vehicle for meropenem. Blood samples were obtained at 0, 15, 30, and 60 min, and then hourly for 6 hr. Sera and extracts of lung tissues were assayed for meropenem content using high-performance liquid chromatography. We found that the IV group had significantly higher serum concentrations of meropenem during the first hour after dosing (P < 0.05). There was no significant difference between IT-PFC and IT-NS groups regarding changes in serum meropenem concentrations during the experimental period. Meropenem content in lung tissue was highest in the IT-PFC group, lower in the IT-NS group, and undetectable in the IV group (P < 0.05). The IT-NS group had the highest peak inspiratory pressure (P < 0.05), but there were no significant differences in other cardiopulmonary parameters among the three groups studied. In conclusion, meropenem can be safely administered to injured lungs by IT instillation in a meropenem/PFC suspension. Using PFC liquid as an IT vehicle to carry meropenem provides better pulmonary drug depositions than IV injection or IT instillation with NS in ALI.

Effects of a perfluorochemical blood substitute on diazepam binding by human albumin.

The binding of 0.4 microgram mL-1 diazepam and 0.75 mol diazepam mol-1 of albumin by a perfluorochemical (PFC) emulsion, Fluosol-DA, 20%, by human serum albumin (HSA), and by their mixtures, has been examined at ambient temperature. The concentration of free diazepam was determined by standard centrifugation followed by supernatant ultrafiltration. Non-specific loss of diazepam occurred to the ultrafiltration device. This loss was independent of drug concentration and a correction factor was employed to calculate the true free diazepam concentration. Diazepam was extensively bound by the PFC emulsion. The percent free diazepam increased as the emulsion concentration decreased, while the binding of diazepam appeared to be independent of drug concentration. Diazepam did not partition into the pure PFC liquids, indicating that emulsion-bound diazepam is only associated with the emulsifiers of the droplets. Diazepam was extensively bound by HSA and the percent free diazepam increased as drug concentration increased or as HSA concentration decreased. The PFC emulsion significantly displaced HSA bound diazepam in all mixtures examined. Studies with the individual and combined components of the emulsion indicated that this displacement is largely attributed to the oleic acid component and, to a much smaller degree, the Pluronic F-68 component of the emulsion.

Liquid Ventilation

Mammals have lungs to breathe air and they have no gills to breath liquids. When the surface tension at the air-liquid interface of the lung increases, as in acute lung injury, scientists started to think about filling the lung with fluid instead of air to reduce the surface tension and facilitate ventilation. Liquid ventilation (LV) is a technique of mechanical ventilation in which the lungs are insufflated with an oxygenated perfluorochemical liquid rather than an oxygen-containing gas mixture. The use of perfluorochemicals, rather than nitrogen, as the inert carrier of oxygen and carbon dioxide offers a number of theoretical advantages for the treatment of acute lung injury. In addition, there are non-respiratory applications with expanding potential including pulmonary drug delivery and radiographic imaging. The potential for multiple clinical applications for liquid-assisted ventilation will be clarified and optimized in future.

A Regulator for Pressure-Controlled Total-Liquid Ventilation

Total-liquid ventilation (TLV) is an innovative experimental method of mechanical-assisted ventilation in which lungs are totally filled and then ventilated with a tidal volume of perfluorochemical liquid by using a dedicated liquid ventilator. Such a novel medical device must resemble other conventional ventilators: it must be able to conduct controlled-pressure ventilation. The objective was to design a robust controller to perform pressure-regulated expiratory flow and to implement it on our latest liquid-ventilator prototype (Inolivent-4). Numerical simulations, in vitro experiments, and in vivo experiments in five healthy term newborn lambs have demonstrated that it was efficient to generate expiratory flows while avoiding collapses. Moreover, the in vivo results have demonstrated that our liquid ventilator can maintain adequate gas exchange, normal acid-base equilibrium, and achieve greater minute ventilation, better oxygenation and CO2 extraction, while nearing flow limits. Hence, it is our suggestion to perform pressure-controlled ventilation during expiration with minute ventilation equal or superior to 140 mL x min(-1) x kg(-1) in order to ensure PaCO2 below 55 mmHg. From a clinician's point of view, pressure-controlled ventilation greatly simplifies the use of the liquid ventilator, which will certainly facilitate its introduction in intensive care units for clinical applications.

Two Distinct Controllers for Pressure Regulation in Total Liquid Ventilation

Total liquid ventilation is an experimental method of mechanical assisted ventilation in which lungs are totally filled and then ventilated with a tidal volume of perfluorochemical liquid by using a liquid ventilator. However to apply this approach to humans, liquid ventilators must reach the same level of reliability as conventional mechanical gas ventilators. In control terms, the problem is to design a controller to perform pressure regulated ventilation in spite of large uncertainties on physiological parameters, and nonlinear behavior of the lungs. The presented pressure controlled ventilation mode is similar to those used in conventional gas ventilator excepted that the airway pressure and the positive end-expiratory pressure require two distinct controllers. Simulations, in-vitro experiments and in-vivo results with 5 healthy term newborn lambs have validated the presented controllers.

Bronchioalveolar lavage with perfluorochemical liquid during conventional ventilation

Therapeutic approaches with bronchioalveolar lavage are currently used in infants with severe alveolar space-occupying material. In many circumstances, bronchioalveolar lavage has been performed in conjunction with extracorporeal membrane oxygenation. A 2-month-old boy with severe respiratory failure requiring assisted ventilation did not respond to any conventional treatments, including surfactant. An open-lung biopsy showed intra-alveolar accumulation of proteinaceous material and foamy macrophages but was not diagnostically conclusive. Therapeutic trials with bronchioalveolar lavage using normal saline were unsuccessful, causing episodes of severe hypoxemia. Then, bronchioalveolar lavage during conventional mechanical ventilation was performed with the use of a medical-grade perfluorochemical liquid (perfluordecalin). After instillation of liquid (10 mL/kg), the lungs were refilled three times during the first 24 hrs and repeated 48 hrs later. During perfluorochemical liquid treatment, the infant's condition remained stable, with small improvements in pulmonary mechanics. Suction from the endotracheal cannula yielded only small amounts of gelatinous material. Considering the progression of the disease and just minimal pulmonary improvements by this intervention, further treatment was considered futile. Support was, thus, minimized, and the infant died a few days later. An autopsy revealed the diagnosis to be consistent with Niemann-Pick C2 disease. This study demonstrated that bronchioalveolar lavage with perfluorochemical liquid could be performed safely during conventional mechanical ventilation without the additional support of extracorporeal membrane oxygenation in infants with severe alveolar space-occupying material.

A supervisor for volume-controlled tidal liquid ventilator using independent piston pumps

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions and lavage of inflammatory debris. This paper presents the control of a total liquid ventilator (TLV) dedicated to ventilate patients with completely filled lungs with a tidal volume of perfluorochemical liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy FRC modifications during ventilation. The prototype was tested on eight healthy term newborn lambs (<5 days old).

Perfluorochemical (PFC) liquid enhances recombinant adenovirus vector-mediated viral interleukin-10 (AdvIL-10) expression in rodent lung

Adenovirus and cationic liposome mediated transfer of Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been shown to decrease pro-inflammatory cytokine levels and overall lung inflammation in models of lung transplantation and injury. Limitations to current approaches of IL-10 gene therapy include poor vector delivery methods and pro-inflammatory properties of human IL-10 under certain conditions. We hypothesize that using perfluorochemical (PFC) liquid to deliver the highly homologous viral IL-10 (vIL-10), which is predominantly anti-inflammatory with minimal pro-inflammatory activities, can potentially be a more effective strategy to combat inflammatory lung diseases. In this study, we compare the use of PFC liquid versus aerosolized method to deliver adenovirus encoding the vIL-10 gene (AdvIL-10) in C57Bl6 mice. Detectable vIL-10 levels were measured from bronchoalveolar lavage fluid and lung homogenates at one, four, ten and thirty days after AdvIL-10. Furthermore, we determined if use of PFC liquid could allow for the use of a lower dose of AdvIL-10 by comparing the levels of detectable vIL-10 at different doses of AdvIL-10 delivered +/- PFC liquid. Results showed that PFC liquid enhanced detectable vIL-10 by up to ten fold and that PFC liquid allowed the use of ten-fold less vector. PFC liquid increased detectable vIL-10 in lung homogenates at all time points; however, the increase in detectable vIL-10 in BAL fluid peaked at four days and was no longer evident by thirty days after intratracheal instillation. In summary, this is the first report utilizing PFC liquid to enhance the delivery of a potentially therapeutic molecule, vIL-10. We believe this strategy can be used to perform future studies on the use of the predominantly anti-inflammatory vIL-10 to treat inflammatory lung diseases.

Effects of perfluorochemical evaporative properties on oxygenation during partial liquid ventilation

The physical-chemical properties of perfluorochemical (PFC) liquids have been shown to influence physiological and cellular responses during partial liquid ventilation (PLV). The aim of this study is to compare the relationship between patho-physiological endpoints and the physical properties of three PFC liquids used in treating acute lung injury. A total of 18 juvenile rabbits were randomized into conventional mechanical ventilation or PLV groups after lung saline lavages. Three PFC liquids, including Flutec perfluoro-1,3,5-trimethylcyclohexane (PP4; vapor pressure, 28.8 mmHg at 37 degrees C), Perfluorodecalin (PFD; vapor pressure, 13.6 mmHg at 37 degrees C), and Perflubron (PFB; vapor pressure, 10.4 mmHg at 37 degrees C) were used for PLV with no replacement for 4 h. A thermal detector was used to measure PFC loss rate. Physiological measurements and evaporative loss rate of PFC were done every 30 min, and lung histology was examined. The mean evaporative loss rate was significantly higher in the PP4 group (4.75 +/- 0.24 mL/kg per h) than in either the PFD (1.43 +/- 0.11 mL/kg per h) or the PFB (1.18 +/- 0.05 mL/kg per h) group (P < 0.05). The oxygenation of PFD and PFB was maintained good for 4 h, however, the PP4 group showed a fast deterioration since 2 h post-treatment due to fast dropping of the residual PP4 amount in lungs. Histology showed good alveolar integrity in the PFD and PFB groups. The effects of PLV are directly influenced by the evaporative property of the PFC liquid. With no replacement over 4 h, PLV effects could be maintained with utilizing a PFC liquid with low, rather than high, vapor pressure. PFC with high vapor pressure has a high loss rate and low residual volume that causes poor maintenance on oxygenation during PLV. Therefore, measuring PFC loss rate is important in future studies and clinical application of PLV.

Liquid Incubator with Perfluorochemicals for Extremely Premature Infants

Objectives: Maintenance of appropriate body temperature, humidification and prevention of skin injury are very important in the management of extremely premature infants with immature skin. We have developed a new closed liquid incubator, utilising the characteristics of perfluorochemical (PFC) liquids, i.e., high specific gravity and chemical and biological inertness. The potential of this incubator to control body temperature was evaluated in rats. Methods: PFC liquid (FC43; 3M Company, Tokyo, Japan) within the incubator was heated or cooled and the rectal temperature of each rat and the PFC temperature were monitored. Results: The rectal temperature of rats floating on the PFC liquid surface changed almost in parallel to the temperature of PFC within the incubator, indicating that this technique can be used to warm or cool adults rats in a stable manner. The relative humidity of air within the incubator was maintained constant at 100%. Conclusions: The liquid incubator used in the present study maintained an environment with a relative humidity of 100% and allowed stable maintenance of temperature in adult rats. We also demonstrated that heating and cooling the PFC liquid allowed control of body temperature. Although further studies are required, this new incubator may be useful for the clinical management of extremely premature infants.

CONTROLLER FOR THE MANAGEMENT OF TIDAL LIQUID VENTILATORS WITH AN INDEPENDENT PUMP SYSTEM

In order to insert and withdraw the tidal volume of perfluorochemical liquid (PFC), the total liquid ventilation (TLV) can be efficiently performed with a pump system. The main originality of the developed prototype is that the expiratory pump is independent of the inspiratory one. Consequently, they are controlled independently. The main advantages are to allow the adjustment of the functional residual capacity (FRC) during ventilations and the optimization of the ventilation cycle. However, two main points must be considered in volume-controlled TLV: avoiding airway closure (chocked flow) during expiration and controlling the FRC volume in the lungs. For this purpose, a controller is implemented to manage the pumping system. The main function of the controller is to control with high precision the volume of liquid to insert and withdraw in the lungs. Due to uncertainties, the pump system generates small volume errors at each inspiratory and expiratory cycle. Over time, the addition of small volume errors may cause an FRC drift. To avoid this problem, the controller monitors the movement of the pumps in order to compute small corrections of the desired inspiratory and expiratory volumes. Consequently, cycle after cycle, the controller learns the command which ensures a constant FRC. In order to withdraw the tidal volume, the controller generates an exponential expiratory profile defined by a time constant. The implementation of this profile is motivated by the need to prevent the risk of airway closure. Moreover, the exponential expiratory profile reproduces the effect of gravity by which the tidal volume of PFC is withdrawn from the lungs. However, even if an exponential is used, airway closures can still appear (if the FRC is too low or the flow velocity is too high). The risk of airway closure during expiration is detected when a negative pressure limit is reached. In this case, the controller stops the expiratory pump, but adjusts the next inspiratory volume in order to ensure a constant FRC in the lungs. Experimental results in vivo and in vitro with newborn lambs confirmed the benefit of using the controller with the exponential expiratory profile. The team is supported in part by the Foundation for Research into Children's Diseases and by the Fonds Québécois pour la Recherche sur la Nature et les Technologies.

Perfluorochemical Liquids Enhance Delivery of Superoxide Dismutase to the Lungs of Juvenile Rabbits

Previous studies suggest acute lung injury (ALI) in premature newborns is associated with relative deficiency of antioxidant enzymes that may be ameliorated by recombinant human superoxide dismutase (rhSOD). Perfluorochemicals (PFCs) are distributed homogeneously and support gas exchange in diseased lungs. We investigated whether PFCs could provide an effective delivery system for rhSOD. Juvenile rabbits were lung-lavaged, treated with surfactant, and randomized: group I: fluorescently labeled rhSOD (5 mg/kg in 2 mL/kg saline); group II: fluorescently labeled rhSOD (5 mg/kg in 18 mL/kg PFC). Animals were ventilated with oxygen for 4 h; the lungs were harvested for analysis of SOD distribution and oxidative injury. Cardiopulmonary indices remained stable and similar between groups. Qualitative assessment (QA) showed a more homogeneous lung SOD distribution in group II and a better histologic profile. QA of lung SOD distribution showed significant increase in SOD concentrations in group II (7.37 +/- 1.54 microg/mg protein) compared with group I (1.65 +/- 0.23 microg/mg protein). Oxidative injury as assessed by normalized protein carbonyl was 149.1 +/- 26.8% SEM in group II compared with 200.5 +/- 7.3% SEM in group I. Plasma SOD was significantly higher in group II. Administration of rhSOD with or without PFCs does not compromise cardiovascular function or impede lung recovery after ALI. PFCs enhance rhSOD delivery to the lungs by 400% while decreasing lung oxidative damage by 25% compared with rhSOD alone. These data suggest that PFCs optimize lung rhSOD delivery and might enhance the beneficial effects of rhSOD in preventing acute and chronic lung injury.

Effects of therapeutic bronchoalveolar lavage and partial liquid ventilation on meconium-aspirated newborn piglets

To investigate the therapeutic effects of bronchoalveolar lavage (BAL) with either diluted surfactant (SBAL) or perfluorochemical liquid (PBAL), followed by either conventional mechanical ventilation (CMV) or partial liquid ventilation (PLV), on lung injury and proinflammatory cytokine production induced by meconium aspiration in newborn piglets. A prospective, randomized, experimental study. An animal research laboratory at a medical center. Anesthetized and mechanically ventilated newborn piglets (n = 27). The animals were instilled with 3-5 mL/kg 25% human meconium via an endotracheal tube to induce meconium aspiration syndrome (MAS). After stabilization, animals were randomly assigned to either CMV group (no BAL) or one of the treatment groups (SBAL-CMV, SBAL-PLV, PBAL-CMV, and PBAL-PLV). Cardiopulmonary variables were monitored, and interleukin-1beta and interleukin-6 content of the serum and lung tissue was measured. The animals without any treatment (CMV group) displayed the worst outcome; the animals in the PBAL-PLV group had the best gas exchange, lung compliance, and least pulmonary damage; and the SBAL-CMV, PBAL-CMV, and SBAL-PLV groups had intermediate effects. The serum interleukin-1beta concentration of the CMV group was significantly higher than all other groups over time (p < .05), and interleukin-6 concentration was significantly higher than the PBAL-PLV group (p < .05). The tissue interleukin-1beta and interleukin-6 contents were also highest in the CMV group and lowest in the PBAL-PLV group. Initial therapeutic BAL and therapeutic BAL followed by PLV with the same perfluorochemical liquid provided significant therapeutic effects in treating an animal model with severe MAS and therefore warrant consideration in cases that are intractable to other therapies.

A SUPERVISOR FOR VOLUME-CONTROLLED TIDAL LIQUID VENTILATOR USING INDEPENDENT PISTON PUMPS

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions and lavage of inflammatory debris. This paper presents the control of a total liquid ventilator (TLV) dedicated to ventilate patients with completely filled lungs with a tidal volume of perfluorochemical liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy FRC modifications during ventilation. The prototype was tested on 5 healthy term newborn lambs (<5 days old).

Pulmonary applications of perfluorochemical liquids: Ventilation and beyond

In this review of liquid ventilation, concepts and applications are presented that summarise the pulmonary applications of perfluorochemical liquids. Beginning with the question of whether this alternative form of respiratory support is needed and ending with lessons learned from clinical trials, the various methods of liquid assisted ventilation are compared and contrasted, evidence for mechanoprotective and cytoprotective attributes of intrapulmonary perfluorochemical liquid are presented and alternative intrapulmonary applications, including their use as vehicles for drugs, for thermal control and as imaging agents are presented.

Differential impact of perfluorochemical physical properties on the physiologic, histologic, and inflammatory profile in acute lung injury

To evaluate the differential effects of physical properties of combinational perfluorochemical liquids (PFC) during partial liquid ventilation (PLV) on inflammatory indexes in the injured lung. : Interventional laboratory study. Academic medical research laboratory. Seventeen saline lavage-injured juvenile rabbits. Rabbits were anesthetized, ventilated, saline lavage-injured, and randomized into groups: group 1 (conventional mechanical ventilation alone-no PFC), group 2 (PLV: lowest viscosity, highest vapor pressure), group 3 (PLV: mid-viscosity, mid-vapor pressure), group 4 (PLV: highest viscosity, lowest vapor pressure). Arterial blood chemistry and pulmonary mechanics were monitored throughout the protocol. Following 4 hrs, lung tissue was harvested for interleukin-8, myeloperoxidase, and histologic analyses. Oxygenation (Pao2), ventilation (ventilation efficiency index), and respiratory compliance were not significantly different between groups before or following injury. Pao2 increased significantly following treatment in groups 3 and 4. Oxygenation index was significantly lower and respiratory compliance and ventilation efficiency index were significantly higher for group 4 following 4 hrs than all other groups. Total lung tissue interleukin-8 was significantly lower in groups 3 and 4 than groups 1 and 2, and lung myeloperoxidase was significantly lower in all PLV-treated groups than CMV alone. Histologic examination showed increased recruitment of the dependent lung in groups 3 and 4, with significantly greater lung expansion index, than groups 1 and 2. PLV, with a single dose of higher viscosity and lower vapor pressure PFC, resulted in significantly improved gas exchange and lung mechanics with significant reduction in lung inflammation compared with conventional mechanical ventilation alone and PLV with lower viscosity and higher vapor pressure liquid. Since PFC evaporative loss and redistribution are minimized by lower VP and higher viscosity, these data suggest that greater mechanoprotection and cytoprotection of the lung are conferred during PLV with PFC liquids that remain distributed throughout the entire lung for a longer duration.