Activated Protein C Decreases Alveolar Protein Leakage in an Animal Model of Ventilator-Induced Lung Injury

Chung-Ming Chen, Leng-Fang Wang

研究成果: 雜誌貢獻文章

摘要

Background: Mechanical ventilation with high tidal volumes can damage the alveolar-capillary barrier and activate a local and systemic inflammation. Objectives: We investigate the effects of activated protein C (APC) on gas exchange, lung cytokine and protein leakage, and systemic fibrinolytic activity in a rat model of ventilator-induced lung injury (VILI).Methods: Male Sprague-Dawley rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP) (HVZP) protocol by a volume-cycled ventilator for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 40 breaths/min, and an FiO2 of 0.21. Fifty minutes before ventilation, the rats received either intravenous APC (500 μg/kg, HVZP + APC group) or normal saline (vehicle for APC; HVZP group). Another group that received no ventilation served as the control.Results: The arterial blood gas tensions were comparable among three study groups before mechanical ventilation. Rats treated with HVZP ventilation exhibited higher mean pH and lower mean carbon dioxide tension than control animals and the arterial blood gas tensions were comparable between HVZP and HVZP + APC groups throughout the study period. HVZP group exhibited significantly higher bronchoalveolar lavage fluid (BALF) protein and plasma D-dimer than did the control group and APC treatment significantly reduced these increments. BALF MIP-2 was significantly higher in rats ventilated with HVZP ventilation than in control animals. HVZP and HVZP + APC groups had a significantly higher lung PAI-1mRNA expression and plasma active PAI-1 level than did the control group.Conclusions: High tidal volume and no PEEP ventilation increase lung alveolar protein leakage, which is attenuated by APC treatment.
原文英語
頁(從 - 到)109-115
頁數7
期刊中華民國兒童胸腔醫學會雜誌
6
發行號4
出版狀態已發佈 - 2010

指紋

Ventilator-Induced Lung Injury
Protein C
Animal Models
Ventilation
Tidal Volume
Proteins
Positive-Pressure Respiration
Gases
Bronchoalveolar Lavage Fluid
Artificial Respiration
Lung
Control Groups
Plasminogen Activator Inhibitor 1
Mechanical Ventilators
Respiratory Rate
Carbon Dioxide
Sprague Dawley Rats
Blood Proteins
Cytokines
Inflammation

引用此文

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title = "Activated Protein C Decreases Alveolar Protein Leakage in an Animal Model of Ventilator-Induced Lung Injury",
abstract = "Background: Mechanical ventilation with high tidal volumes can damage the alveolar-capillary barrier and activate a local and systemic inflammation. Objectives: We investigate the effects of activated protein C (APC) on gas exchange, lung cytokine and protein leakage, and systemic fibrinolytic activity in a rat model of ventilator-induced lung injury (VILI).Methods: Male Sprague-Dawley rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP) (HVZP) protocol by a volume-cycled ventilator for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 40 breaths/min, and an FiO2 of 0.21. Fifty minutes before ventilation, the rats received either intravenous APC (500 μg/kg, HVZP + APC group) or normal saline (vehicle for APC; HVZP group). Another group that received no ventilation served as the control.Results: The arterial blood gas tensions were comparable among three study groups before mechanical ventilation. Rats treated with HVZP ventilation exhibited higher mean pH and lower mean carbon dioxide tension than control animals and the arterial blood gas tensions were comparable between HVZP and HVZP + APC groups throughout the study period. HVZP group exhibited significantly higher bronchoalveolar lavage fluid (BALF) protein and plasma D-dimer than did the control group and APC treatment significantly reduced these increments. BALF MIP-2 was significantly higher in rats ventilated with HVZP ventilation than in control animals. HVZP and HVZP + APC groups had a significantly higher lung PAI-1mRNA expression and plasma active PAI-1 level than did the control group.Conclusions: High tidal volume and no PEEP ventilation increase lung alveolar protein leakage, which is attenuated by APC treatment.",
keywords = "bronchoalveolar lavage, dimmer, macrophage inflammatory protein-2, plasminogen activator inhibitor-1",
author = "Chung-Ming Chen and Leng-Fang Wang",
year = "2010",
language = "English",
volume = "6",
pages = "109--115",
journal = "中華民國兒童胸腔醫學會雜誌",
issn = "2221-1837",
publisher = "中華民國兒童胸腔醫學會",
number = "4",

}

TY - JOUR

T1 - Activated Protein C Decreases Alveolar Protein Leakage in an Animal Model of Ventilator-Induced Lung Injury

AU - Chen, Chung-Ming

AU - Wang, Leng-Fang

PY - 2010

Y1 - 2010

N2 - Background: Mechanical ventilation with high tidal volumes can damage the alveolar-capillary barrier and activate a local and systemic inflammation. Objectives: We investigate the effects of activated protein C (APC) on gas exchange, lung cytokine and protein leakage, and systemic fibrinolytic activity in a rat model of ventilator-induced lung injury (VILI).Methods: Male Sprague-Dawley rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP) (HVZP) protocol by a volume-cycled ventilator for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 40 breaths/min, and an FiO2 of 0.21. Fifty minutes before ventilation, the rats received either intravenous APC (500 μg/kg, HVZP + APC group) or normal saline (vehicle for APC; HVZP group). Another group that received no ventilation served as the control.Results: The arterial blood gas tensions were comparable among three study groups before mechanical ventilation. Rats treated with HVZP ventilation exhibited higher mean pH and lower mean carbon dioxide tension than control animals and the arterial blood gas tensions were comparable between HVZP and HVZP + APC groups throughout the study period. HVZP group exhibited significantly higher bronchoalveolar lavage fluid (BALF) protein and plasma D-dimer than did the control group and APC treatment significantly reduced these increments. BALF MIP-2 was significantly higher in rats ventilated with HVZP ventilation than in control animals. HVZP and HVZP + APC groups had a significantly higher lung PAI-1mRNA expression and plasma active PAI-1 level than did the control group.Conclusions: High tidal volume and no PEEP ventilation increase lung alveolar protein leakage, which is attenuated by APC treatment.

AB - Background: Mechanical ventilation with high tidal volumes can damage the alveolar-capillary barrier and activate a local and systemic inflammation. Objectives: We investigate the effects of activated protein C (APC) on gas exchange, lung cytokine and protein leakage, and systemic fibrinolytic activity in a rat model of ventilator-induced lung injury (VILI).Methods: Male Sprague-Dawley rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP) (HVZP) protocol by a volume-cycled ventilator for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 40 breaths/min, and an FiO2 of 0.21. Fifty minutes before ventilation, the rats received either intravenous APC (500 μg/kg, HVZP + APC group) or normal saline (vehicle for APC; HVZP group). Another group that received no ventilation served as the control.Results: The arterial blood gas tensions were comparable among three study groups before mechanical ventilation. Rats treated with HVZP ventilation exhibited higher mean pH and lower mean carbon dioxide tension than control animals and the arterial blood gas tensions were comparable between HVZP and HVZP + APC groups throughout the study period. HVZP group exhibited significantly higher bronchoalveolar lavage fluid (BALF) protein and plasma D-dimer than did the control group and APC treatment significantly reduced these increments. BALF MIP-2 was significantly higher in rats ventilated with HVZP ventilation than in control animals. HVZP and HVZP + APC groups had a significantly higher lung PAI-1mRNA expression and plasma active PAI-1 level than did the control group.Conclusions: High tidal volume and no PEEP ventilation increase lung alveolar protein leakage, which is attenuated by APC treatment.

KW - bronchoalveolar lavage

KW - dimmer

KW - macrophage inflammatory protein-2

KW - plasminogen activator inhibitor-1

M3 - Article

VL - 6

SP - 109

EP - 115

JO - 中華民國兒童胸腔醫學會雜誌

JF - 中華民國兒童胸腔醫學會雜誌

SN - 2221-1837

IS - 4

ER -