Effects of activated protein c on ventilator-induced lung injury in rats

Jiunn Song Jiang, Hsiu Chu Chou, Leng Fang Wang, Yaw Dong Lang, Chung Ming Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. Objectives: The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. Methods: 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 VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO 2 of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 μg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. Results: Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. Conclusions: These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.

Original languageEnglish
Pages (from-to)246-253
Number of pages8
JournalRespiration
Volume80
Issue number3
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Ventilator-Induced Lung Injury
Protein C
Plasminogen Activator Inhibitor 1
Lung
Proteins
Ventilation
Bronchoalveolar Lavage Fluid
Chemokine CXCL2
Plasminogen Inactivators
Control Groups
Positive-Pressure Respiration
Tidal Volume
Fibrinolysis
Mechanical Ventilators
Respiratory Rate
Conditioned Culture Medium
Fibrin
Artificial Respiration
Histology
Endothelial Cells

Keywords

  • Bronchoalveolar lavage
  • Dimers
  • Macrophage inflammatory protein-2
  • Plasminogen activator inhibitor-1
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effects of activated protein c on ventilator-induced lung injury in rats. / Jiang, Jiunn Song; Chou, Hsiu Chu; Wang, Leng Fang; Lang, Yaw Dong; Chen, Chung Ming.

In: Respiration, Vol. 80, No. 3, 08.2010, p. 246-253.

Research output: Contribution to journalArticle

Jiang, Jiunn Song ; Chou, Hsiu Chu ; Wang, Leng Fang ; Lang, Yaw Dong ; Chen, Chung Ming. / Effects of activated protein c on ventilator-induced lung injury in rats. In: Respiration. 2010 ; Vol. 80, No. 3. pp. 246-253.
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N2 - Background: Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. Objectives: The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. Methods: 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 VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO 2 of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 μg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. Results: Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. Conclusions: These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.

AB - Background: Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. Objectives: The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. Methods: 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 VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO 2 of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 μg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. Results: Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. Conclusions: These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.

KW - Bronchoalveolar lavage

KW - Dimers

KW - Macrophage inflammatory protein-2

KW - Plasminogen activator inhibitor-1

KW - Ventilator-induced lung injury

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