Angiotensin-converting enzyme inhibitor captopril attenuates ventilator-induced lung injury in rats

Jiang, Jiunn Song; Wang, Leng-Fang; Chou, Hsiu Chu; Chen, Chung-Ming

doi:10.1152/japplphysiol.00514.2006

Cited by 36 publications

(33 citation statements)

References 33 publications

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“…Many studies have shown that severe lung injury is provoked by ventilation with high tidal volumes. [15][16][17] Although the exact underlying mechanisms of VILI remain undefined, several potential pathways have been proposed, with barotrauma appearing to be the generally accepted one. In our study, significant infiltration of neutrophils was observed on pathological examination of the lung tissue exposed to high tidal volume ventilation.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Xiong¹,

Lin²,

Wang³

2013

IJN

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Background: Mechanical ventilation has been documented to paradoxically cause lung injury. As a commonly used volatile anesthetic, sevoflurane has been proven to possess antiinflammatory and antioxidative properties. This study aims to investigate the protective effects of sevoflurane on inflammation and ventilator-induced lung injury during mechanical ventilation in healthy mice. Methods: The adult healthy mice were divided into four groups, each consisting of ten subjects: mice in group Con-L VT and group Sev-L VT were ventilated with tidal volumes of 8 mL/kg for 4 hours, while those in group Con-H VT and group Sev-H VT were ventilated with tidal volumes of 16 mL/kg instead. Control mice (group Con-L VT and Con-H VT ) were subjected to fresh air, while sevoflurane-treated mice (groups Sev-L VT and Sev-H VT ) were subjected to air mixed with 1 vol% sevoflurane. After 4 hours of ventilation, the bronchoalveolar lavage (BAL) fluid was collected and analyzed for the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10. Lung homogenates were harvested to detect the expression of nuclear factorkappa B (NF-κB) and heme oxygenase (HO)-1 mRNA by reverse transcription-polymerase chain reaction method. Lung damage was evaluated using the modified Ventilator-Induced Lung Injury histological scoring system. Results: Compared to group Con-L VT , the levels of TNF-α, IL-1β, IL-6, and IL-10 in BAL fluid, mRNA expressions of NF-κB and HO-1 in lung tissue, and lung injury scores were significantly increased in group Con-H VT ; compared to group Con-H VT , group Sev-H VT BAL samples showed decreased levels of TNF-α, IL-1β, and IL-6; they also showed increased levels of IL-10, the downregulation of NF-κB mRNA, and HO-1 mRNA upregulation; the lung injury scores were significantly lower in group Sev-H VT than group Con-H VT . Conclusion: Mechanical ventilation with high tidal volume might lead to lung injury, which could be significantly, but not completely, attenuated by sevoflurane inhalation by inhibiting the NF-κB-mediated proinflammatory cytokine generation and upregulating HO-1 expression.

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Section: Discussionmentioning

confidence: 99%

Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Xiong¹,

Lin²,

Wang³

2013

IJN

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“…The anti-inflammatory activity of APC depends on its ability to suppress the secretion of several cytokines [29]. MIP-2 is associated with leukocyte migration and activation, and was found to be closely associated with them in animal models of pneumonia and VILI [30,31]. Intravenous APC significantly decreased BALF levels of MIP-2 in leukocyte elastase-induced lung injury in mice [32].…”

Section: Discussionmentioning

confidence: 99%

Effects of Activated Protein C on Ventilator-Induced Lung Injury in Rats

Jiang

Chou²,

Wang

et al. 2010

Respiration

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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 FiO₂ 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.

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“…MIP-2 is associated with leukocyte migration and activation and has been found to be closely associated with animal models of pneumonia and VILI [27,28] . In this study, although lung vascular fibrin deposition was significantly decreased, the BALF levels of MIP-2 were not decreased in the HVZP+tPA group.…”

Section: Discussionmentioning

confidence: 99%

“…These changes imply that the fibrinolytic effect of tPA is independent of its anti-inflammatory activity. Although tPA influences neutrophil function in vitro, no data exists regarding the effect of exogenous tPA on MIP-2 levels in vivo [27] . In this study, we found that tPA treatment decreased HVZP ventilation-induced increases in plasma D-dimers but did not decrease BALF levels of MIP-2.…”

Section: Discussionmentioning

confidence: 99%

Tissue plasminogen activator attenuates ventilator-induced lung injury in rats

Huang¹,

Chou²,

Wang³

et al. 2012

Acta Pharmacol Sin

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Aim: To test the hypothesis that the tissue plasminogen activator (tPA) may counteract the inhibitory effect of plasminogen activator inhibitors (PAI) and attenuate lung injury in a rat model of ventilator-induced lung injury (VILI). Methods: Adult male Sprague-Dawley rats were ventilated with a HVZP (high-volume zero PeeP) protocol for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 25 breaths/min, and an inspired oxygen fraction of 21%. The rats were divided into 3 groups (n=7 for each): HVZP+tPA group receiving tPA (1.25 mg/kg, iv) 15 min before ventilation, HVZP group receiving HVZP+vehicle injection, and a control group receiving no ventilation. After 2 h of ventilation, the rats were killed; blood and lungs were collected for biochemical and histological analyses. Results: HVZP ventilation significantly increased total protein content and the concentration of macrophage inflammatory protein-2 (MIP-2) in the bronchoalveolar lavage fluid (BALF) as well as the lung injury score. Rats that received HVZP ventilation had significantly higher lung PAI-1 mRNA expression, plasma PAI-1 and plasma D-dimer levels than the control animals. tPA treatment significantly reduced the BALF total protein and the lung injury score as compared to the HVZP group. tPA treatment also significantly decreased the plasma D-dimer levels and the HVZP ventilation-induced lung vascular fibrin thrombi. tPA treatment showed no effect on MIP-2 level in BALF.Conclusion: These results demonstrate that VILI increases lung PAI-1 mRNA expression, plasma levels of PAI-1 and D-dimers, lung injury score and vascular fibrin deposition. tPA can attenuate VILI by decreasing capillary-alveolar protein leakage as well as local and systemic coagulation as shown by decreased lung vascular fibrin deposition and plasma D-dimers.

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Angiotensin-converting enzyme inhibitor captopril attenuates ventilator-induced lung injury in rats

Cited by 36 publications

References 33 publications

Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Effects of Activated Protein C on Ventilator-Induced Lung Injury in Rats

Tissue plasminogen activator attenuates ventilator-induced lung injury in rats

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