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

Jeng, Mei Jy; Yang, Shih-Chieh; Wolfson, Marla R.; Shaffer, Thomas H.

doi:10.1203/00006450-200301000-00015

Cited by 19 publications

(21 citation statements)

References 38 publications

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“…As shown in this study, the rhSOD/PFC group had similar physiologic and histologic profiles as in previously treated PFC (25% PP2/75% PP9) alone groups (27). Compared with untreated lung-injured rabbits (21), groups treated with PFC alone, rhSOD/PFC, or rhSOD/saline demonstrated better gas exchange and lung function over the 4-h study period.…”

Section: Discussionsupporting

confidence: 72%

“…More recently, the combination of two PFC fluids has been shown to be particularly effective for treatment of ALI (27). As shown in this study, the rhSOD/PFC group had similar physiologic and histologic profiles as in previously treated PFC (25% PP2/75% PP9) alone groups (27).…”

Section: Discussionsupporting

confidence: 70%

“…The PFC liquid was a mixture of 25% perfluoromethylcyclohexane (PP2) and 75% perfluoromethyldecalin (PP9) (F2 Chemicals Corp., Preston, U.K.). This mixture provides better gas exchange, compliance, and histologic findings after ALI as described in our laboratory (27).…”

Section: Methodsmentioning

confidence: 96%

“…Half the animals in each group received rhodamine-conjugated rhSOD. We have previously reported physiologic and histologic data from this lung injury model over 4 h in an untreated mechanically ventilated group, as well as a PFC (25% PP2/75% PP9) alone group (21,27).…”

Section: Methodsmentioning

confidence: 99%

“…Also, we examined whether PFCmediated administration of rhSOD would enhance lung distribution of the enzyme and, in the short term, decrease markers of oxidative damage. Finally, physiologic and histologic comparisons of SOD treatment groups are discussed within the context of published data from untreated animals and those treated with PFC alone (21)(22)(23)(24)(25)(26)(27).…”

mentioning

confidence: 99%

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

et al. 2006

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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 Ϯ 1.54 g/mg protein) compared with group I (1.65 Ϯ 0.23 g/mg protein). Oxidative injury as assessed by normalized protein carbonyl was 149.1 Ϯ 26.8% SEM in group II compared with 200.5 Ϯ 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. (Pediatr Res 60: 65-70, 2006)

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Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 70%

Section: Methodsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2006

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Application of hydrocarbon and perfluorocarbon oxygen vectors to enhance heterologous production of hyaluronic acid in engineered Bacillus subtilis

Westbrook

Ren

Moo‐Young

et al. 2018

Biotech & Bioengineering

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In microbial cultivations for hyaluronic acid (HA) production, oxygen can be a limiting substrate due to its poor solubility in aqueous medium and the substantial increase in culture viscosity at relatively low HA titers. Shear stress due to the high agitation and aeration rates required to overcome oxygen limitation may reduce the quality (i.e., molecular weight) of HA, and production costs associated with power consumption and supplemental oxygen may be excessive. Here, we report the application of oxygen vectors to the heterologous production of HA in engineered Bacillus subtilis, leading to significantly improved culture performance. We first derived an improved HA-producing strain of B. subtilis through engineering of the promoter driving coexpression of seHas and tuaD, leading to high-level HA production. Out of seven potential oxygen vectors evaluated in a preliminary screening, significant improvements to the HA titer and/or cell density were observed in cultures containing n-heptane, n-hexadecane, perfluoromethyldecalin, and perfluoro-1,3-dimethylcyclohexane. Adjustments to the vector concentration, timing of vector addition, and the agitation rate resulted in further enhancements, with the HA titer reaching up to 4.5 g/L after only 10 hr cultivation. Moreover, our results indicate that certain vectors may alter the functional expression of Class I hyaluronan synthase (HAS) in B. subtilis, and that higher shear rates may drive more carbon flux through the HA biosynthetic pathway without negatively affecting the MW. Our study demonstrates the efficacy of oxygen vectors to enhance heterologous HA production in B. subtilis, and provides valuable insight for future bioprocess development in microbial HA production.

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Tracheal gas insufflation‐augmented continuous positive airway pressure in a spontaneously breathing model of neonatal respiratory distress

Miller

Blackson

Shaffer

et al. 2004

Pediatric Pulmonology

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Respiratory distress syndrome (RDS) in neonates is characterized by labored breathing and poor gas exchange, often requiring ventilatory support. Continuous positive airway pressure (CPAP) is a preferred intervention to support spontaneous ventilatory efforts by sustaining lung volume recruitment, while it prevents derecruitment during exhalation by maintaining end-expiratory pressure. However, CO2 retention during CPAP often results in the need for mechanical ventilation. Since tracheal gas insufflation (TGI) promotes CO2 elimination by reducing prosthetic dead space, we hypothesized that TGI used with CPAP may reduce the need for more invasive therapies. The objective of this study was to evaluate the physiologic effect of TGI with CPAP in a spontaneously breathing model of acute lung injury with respect to gas exchange and pulmonary mechanics. Nineteen spontaneously breathing neonatal pigs (2.4 +/- 0.4 kg) were anesthetized, sedated, instrumented, and placed on CPAP at 5 cmH2O. All piglets were injured with intravenous oleic acid (0.08 ml/kg), and then randomized to receive CPAP with TGI (TGI; n = 9) or CPAP alone (control; n = 10). FiO2 was titrated at 0.05 every 15 min during the protocol to maintain SaO2 > 93%. Vital signs, arterial blood gases, pulmonary mechanics, and thoracoabdominal motion (TAM) were evaluated 30 min after injury and at 1-hr intervals for 4 hr. Following the 4-hr measurement, the piglets were sacrificed and the lungs were grossly examined. After initiation of treatment, we found that the PaCO2 was lower (33.1 +/- 5.0 vs. 47.0 +/- 10.3 mmHg; P < 0.01), while the oxygenation indices were greater (PaO2, SaO2, a/A ratio; P < 0.01) in the TGI group than with control animals. Subsequently, the pH was greater (7.45 +/- 0.08 vs. 7.36 +/- 0.08; P < 0.01) and closer to baseline values with TGI. By 4 hr, the FiO2 was titrated lower (0.37 +/- 0.06 vs. 0.49 +/- 0.15; P < 0.05) and ventilation was accomplished with a lower minute ventilation (MV) in the TGI group than in the control group (445 +/- 113 vs. 581 +/- 223 ml/kg/min; P < 0.01). Respiratory compliance was greater with TGI than control (0.76 +/- 0.13 vs. 0.63 +/- 0.11 ml/cmH2O/kg; P < 0.01), whereas resistance and TAM were similar between groups. We conclude that the use of TGI with CPAP in the treatment of RDS results in improved gas exchange and pulmonary mechanics. As such, TGI-augmented CPAP may prevent infants from requiring more invasive ventilation by reducing CO2 retention.

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

Cited by 19 publications

References 38 publications

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

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

Application of hydrocarbon and perfluorocarbon oxygen vectors to enhance heterologous production of hyaluronic acid in engineered Bacillus subtilis

Tracheal gas insufflation‐augmented continuous positive airway pressure in a spontaneously breathing model of neonatal respiratory distress

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