Improvement of Gas Exchange, Pulmonary Function, and Lung Injury With Partial Liquid Ventilation

Hirschl, Ronald B.; Tooley, Richard; Parent, Alan; Johnson, Kent J.; Bartlett, Robert H.

doi:10.1378/chest.108.2.500

Cited by 142 publications

(65 citation statements)

References 41 publications

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“…In the last few years, several clinical studies have been published focusing on the use of PLV in premature infants as well as in adult ARDS (3,4). However, until now the mechanisms by which PLV improves gas exchange and pulmonary function were not completely understood.…”

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confidence: 99%

¹⁹F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

Laukemper-Ostendorf

Scholz

Bürger

et al. 2001

Magnetic Resonance in Med

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Perfluorocarbon compounds (PFCs) have received increasing interest for medical applications because of the high solubility of gases like O 2 and CO 2 in these substances (1). In addition, the suitability of PFCs as a respiratory medium is favored by their low surface tension and biological inertness. With the intrapulmonary application of PFCs, a new therapeutic strategy for the treatment of acute respiratory distress syndrome (ARDS) was developed. This technique is called partial liquid ventilation (PLV) and was first described by Fuhrman et al. in 1991 (2).During PLV, gas exchange is achieved by delivering gas tidal volumes into a lung which has previously been filled with a PFC. In the last few years, several clinical studies have been published focusing on the use of PLV in premature infants as well as in adult ARDS (3,4). However, until now the mechanisms by which PLV improves gas exchange and pulmonary function were not completely understood. Numerous studies have examined the influence of PLV on pulmonary gas exchange and systemic blood gas parameters. Although knowledge of the regional distribution of intrapulmonary oxygen partial pressure (pO2) during PLV is crucial for the understanding of PLV, this distribution has not been measured before.Recently, several methods for quantitative determination of pO2 based on 19 F-MRI of perfluorocarbon compounds have been suggested (1,5-9). Paramagnetic oxygen reduces the longitudinal relaxation time (T 1 ) of the 19 F MR resonances in PFCs. This effect can be used for the generation of an oxygen-dependent MR signal intensity in T 1 -weighted images. Nö th et al. (8) presented a technique based on a chemical shift selective (CHESS) TurboFLASH sequence allowing for the determination of regional pO2. In their study, that sequence was applied in vivo to investigate the regional distribution of pO2 in rats after intravenous injection of a perfluorocarbon emulsion.The first objective of this study was to develop a technique for a visualization of the intrapulmonary distribution of PFC during PLV with high spatial resolution. The second objective was to develop a methodology for the quantification of regional pO2 during PLV of pigs. Special consideration was given to suppress systematic errors by noise and results of a pilot study using this new technique in a healthy pig during PLV are presented. MATERIALS AND METHODS Measurements Experimental SetupAll data were acquired on a 1.5 T Siemens Magnetom Vision whole body scanner with a prototype gradient system (50 mT/m, slew rate 160 mT m -1 ms -1 ). A birdcage RF coil (RAPID Biomedical GmbH, Wü rzburg, Germany) was used for RF transmission and reception. The fluorinated contrast agent used in the animal study was neat liquid perfluoro-octyl-bromide (PFOB) C 8 F 17 Br (LiquiVent , Alliance Pharm. Corp., San Diego, CA, USA).With animal committee approval, in vivo measurements were performed in a healthy, anesthetized pig (body weight, 18 kg) under conditions of PLV. The lungs were filled in part with 20 mL PFOB/kg body weigh...

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¹⁹F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

Laukemper-Ostendorf

Scholz

Bürger

et al. 2001

Magnetic Resonance in Med

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“…In our previous studies, we found that a PFC liquid with high vapor pressure, such as FC-77 (vapor pressure, 85 mm Hg at 37°C and 42 mm Hg at 25°C) would need more frequent replacement (approximately 10 mL·kg Ϫ1 ·h Ϫ1 ) than perflubron (1-5 mL·kg Ϫ1 ·h Ϫ1 ), which is commonly used in animal studies and clinical trials (10,11,20,21). In addition, in other studies we found that a PFC liquid with high viscosity, such as perfluorodecalin (viscosity, 2.61 cS), could not maintain oxygenation in clinically acceptable levels compared with studies with perflubron for 4 h (12,20).…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…Liquid-assisted ventilation, filling the lungs with PFC liquids during mechanical ventilation, including TLV and PLV, has proven effective in treating acute respiratory failure of premature, neonatal, and adult lungs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The properties of different PFC liquids influence physiologic and cellular responses during PLV and affect the dosing strategy (1, 2); however, there are a limited number of PFC fluids appropriate for respiratory applications.…”

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confidence: 99%

“…The properties of different PFC liquids influence physiologic and cellular responses during PLV and affect the dosing strategy (1, 2); however, there are a limited number of PFC fluids appropriate for respiratory applications. Although several PFC liquids have been reported for liquid-assisted ventilation, including TLV and PLV (10,(12)(13)(14)(15)(16)(17)(18), there have been no studies exploring the effects of combining different PFC liquids to produce a fluid with optimum physical properties for respiratory therapy.…”

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Perfluorochemical (PFC) Combinations for Acute Lung Injury: An In Vitro and In Vivo Study in Juvenile Rabbits

Jeng

2003

Pediatric Research

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Perfluorochemical (PFC) fluids of different physical properties were titrated and tested in vitro for physical properties that are appropriate for respiratory application. Two PFC liquids were studied: perfluoromethylcyclohexane (PP2), a liquid with high vapor pressure and low viscosity, and perfluoromethyldecalin (PP9), a fluid with low vapor pressure and high viscosity. Eighteen rabbits (2.05 Ϯ 0.07 kg; mean Ϯ SEM) were lunglavaged and randomized: group I, control group; group II, partial liquid ventilation with 75% PP2 and 25% PP9; group III, partial liquid ventilation with 50% PP2 and 50% PP9; and group IV, partial liquid ventilation with 25% PP2 and 75% PP9. Ventilator volumes were kept constant during the 4-h experiment. Cardiopulmonary measurements were performed every 30 min. The lung histology was examined. The in vitro study showed PFC [viscosity/vapor pressure (in cS and mm Hg, respectively)] as follows: 100% PP2 (0.88/141); 100% PP9 (3.32/2.9); 75% PP2 and 25% PP9 (1.26/107); 50% PP2 and 50% PP9 (1.63/13.7); and 25% PP2 and 75% PP9 (2.21/4.4). The in vivo experiments found that combinations of moderate vapor pressure (groups 3 and 4) demonstrated good gas exchange, compliance, and histo- The use of PFC as a medical material has been investigated during the past decades (1, 2). Liquid-assisted ventilation, filling the lungs with PFC liquids during mechanical ventilation, including TLV and PLV, has proven effective in treating acute respiratory failure of premature, neonatal, and adult lungs (1-11). The properties of different PFC liquids influence physiologic and cellular responses during PLV and affect the dosing strategy (1, 2); however, there are a limited number of PFC fluids appropriate for respiratory applications. Although several PFC liquids have been reported for liquid-assisted ventilation, including TLV and PLV (10, 12-18), there have been no studies exploring the effects of combining different PFC liquids to produce a fluid with optimum physical properties for respiratory therapy.All PFC liquids are immiscible to water, but they are soluble in each other (1). A PFC liquid suitable for respiratory application has the properties of high gas solubility and moderate vapor pressure and viscosity (2). Inasmuch as only a few PFC liquids are good candidates as a respiratory medium, a mixture

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“…Although liquid ventilation has generally fallen from clinical use, administration of perflubron (LiquiVent; Alliance Pharmaceutical, San Diego, CA) and other PFC liquids in PLV was safe and could improve oxygenation and lung mechanics while also decreasing histopathological injury and inflammation in injured lungs (Hirschl et al, 1995(Hirschl et al, , 2002Leach et al, 1996;Rotta et al, 1999;Kacmarek et al, 2006). More recently it has been found that inhalation of nebulized perflubron and other PFC compounds comparably enhances oxygenation and improves lung mechanics in preclinical models of lung injury (Bleyl et al, 1999;Kandler et al, 2001Kandler et al, , 2004Ragaller et al, 2001;von der Hardt et al, 2004;Gama de Abreu et al, 2005;Meinhardt et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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

Beckett

Bonneau

Howard

et al. 2012

Human Gene Therapy Methods

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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.

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Improvement of Gas Exchange, Pulmonary Function, and Lung Injury With Partial Liquid Ventilation

Cited by 142 publications

References 41 publications

¹⁹F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

¹⁹F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

Perfluorochemical (PFC) Combinations for Acute Lung Injury: An In Vitro and In Vivo Study in Juvenile Rabbits

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

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Improvement of Gas Exchange, Pulmonary Function, and Lung Injury With Partial Liquid Ventilation

Cited by 142 publications

References 41 publications

19F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

19F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

Perfluorochemical (PFC) Combinations for Acute Lung Injury: An In Vitro and In Vivo Study in Juvenile Rabbits

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

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¹⁹F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation

¹⁹F‐MRI of perflubron for measurement of oxygen partial pressure in porcine lungs during partial liquid ventilation