scholarly journals Mild hypothermia attenuates changes in respiratory system mechanics and modifies cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation

2010 ◽  
pp. 937-944
Author(s):  
P Dostál ◽  
M Šenkeřík ◽  
R Pařízková ◽  
D Bareš ◽  
P Živný ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Respiratory System ◽  
Bronchoalveolar Lavage Fluid ◽  
Mild Hypothermia ◽  
Lavage Fluid ◽  
Cytokine Concentration ◽  
Volume Ventilation ◽  
Hypothermia Group

Hypothermia was shown to attenuate ventilator-induced lung injury due to large tidal volumes. It is unclear if the protective effect of hypothermia is maintained under less injurious mechanical ventilation in animals without previous lung injury. Tracheostomized rats were randomly allocated to non-ventilated group (group C) or ventilated groups of normothermia (group N) and mild hypothermia (group H). After two hours of mechanical ventilation with inspiratory fraction of oxygen 1.0, respiratory rate 60 min-1, tidal volume 10 ml·kg-1, positive end-expiratory pressure (PEEP) 2 cm H2O or immediately after tracheostomy in non-ventilated animals inspiratory pressures were recorded, rats were sacrificed, pressure-volume (PV) curve of respiratory system constructed, bronchoalveolar lavage (BAL) fluid and aortic blood samples obtained. Group N animals exhibited a higher rise in peak inspiratory pressures in comparison to group H animals. Shift of the PV curve to right, higher total protein and interleukin6 levels in BAL fluid were observed in normothermia animals in comparison with hypothermia animals and non-ventilated controls. Tumor necrosis factor-α was lower in the hypothermia group in comparison with normothermia and non-ventilated groups. Mild hypothermia attenuated changes in respiratory system mechanics and modified cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation in animals without previous lung injury.

scholarly journals Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Pulmonary Inflammation in Patients without Preexisting Lung Injury

2008 ◽  
Vol 108 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Esther K. Wolthuis ◽  
Goda Choi ◽  
Mark C. Dessing ◽  
Paul Bresser ◽  
Rene Lutter ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Positive End Expiratory Pressure ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Background Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Methods Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Results Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups. Conclusion The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

YAP Expression in Endothelial Cells Prevents Ventilator-induced Lung Injury

2021 ◽  
Author(s):  
Kai Su ◽  
Jianguo Wang ◽  
Yang Lv ◽  
Ming Tian ◽  
You-Yang Zhao ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Endothelial Cells ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Protein Content ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Ventilator Induced Lung Injury

Ventilator-induced lung injury is associated with an increase in mortality in patients with respiratory dysfunction, although mechanical ventilation is an essential intervention implemented in the intensive care unit. Intrinsic molecular mechanisms for minimizing lung inflammatory injury during mechanical ventilation remain poorly defined. We hypothesize that Yes-associated protein (YAP) expression in endothelial cells protects the lung against ventilator-induced injury. Wild type and endothelial-specific YAP-deficient mice were subjected to a low (7 ml/kg) or high (21 ml/kg) tidal volume (VT) ventilation for 4 h. Infiltration of inflammatory cells into the lung, vascular permeability, lung histopathology, and the levels of inflammatory cytokines were measured. Here we showed that mechanical ventilation with high VT up-regulated YAP protein expression in pulmonary endothelial cells. Endothelial-specific YAP knockout mice following high VT ventilation exhibited increased neutrophil counts and protein content in bronchoalveolar lavage fluid, Evans blue leakage and histological lung injury compared to wild-type littermate controls. Deletion of YAP in endothelial cells exaggerated vascular endothelial (VE)-cadherin phosphorylation, downregulation of vascular endothelial protein tyrosine phosphatase (VE-PTP) and dissociation of VE-cadherin and catenins following mechanical ventilation. Importantly, exogenous expression of wild type VE-PTP in the pulmonary vasculature rescued YAP ablation-induced increases in neutrophil counts and protein content in bronchoalveolar lavage fluid, vascular leakage, and histological lung injury as well as VE-cadherin phosphorylation and dissociation from catenins following ventilation. These data demonstrate that YAP expression in endothelial cells suppresses lung inflammatory response and edema formation by modulating VE-PTP-mediated VE-cadherin phosphorylation and thus plays a protective role in ventilator-induced lung injury.

Mechanical Ventilation Induces Neutrophil Extracellular Trap Formation

2015 ◽  
Vol 122 (4) ◽  
pp. 864-875 ◽  
Author(s):  
Christopher Yildiz ◽  
Nades Palaniyar ◽  
Gail Otulakowski ◽  
Meraj A. Khan ◽  
Martin Post ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
High Mobility ◽  
Lavage Fluid ◽  
High Mobility Group ◽  
Interleukin 1Β ◽  
Histone 3 ◽  
Dnase Treatment

Abstract Background: Mechanical ventilation can injure the lung and induce a proinflammatory state; such ventilator-induced lung injury (VILI) is associated with neutrophil influx. Neutrophils release DNA and granular proteins as cytotoxic neutrophil extracellular traps (NETs). The authors hypothesized that NETs were produced in a VILI model and may contribute to injury. Methods: In a two-hit lipopolysaccharide/VILI mouse model with and without intratracheal deoxyribonuclease (DNase) treatment or blockade of known inducers of NET formation (NETosis), the authors assessed compliance, bronchoalveolar lavage fluid protein, markers of NETs (citrullinated histone-3 and DNA), and markers of inflammation. Results: Although lipopolysaccharide recruited neutrophils to airways, the addition of high tidal mechanical ventilation was required for significant induction of NETs markers (e.g., bronchoalveolar lavage fluid DNA: 0.4 ± 0.07 µg/ml [mean ± SEM], P < 0.05 vs. all others, n = 10 per group). High tidal volume mechanical ventilation increased airway high-mobility group box 1 protein (0.91 ± 0.138 vs. 0.60 ± 0.095) and interleukin-1β in lipopolysaccharide-treated mice (22.4 ± 0.87 vs. 17.0 ± 0.50 pg/ml, P < 0.001) and tended to increase monocyte chemoattractant protein-1 and interleukin-6. Intratracheal DNase treatment reduced NET markers (bronchoalveolar lavage fluid DNA: 0.23 ± 0.038 vs. 0.88 ± 0.135 µg/ml, P < 0.001; citrullinated histone-3: 443 ± 170 vs. 1,824 ± 403, P < 0.01, n = 8 to 10) and attenuated the loss of static compliance (0.9 ± 0.14 vs. 1.58 ± 0.17 ml/mmHg, P < 0.01, n = 19 to 20) without significantly impacting other measures of injury. Blockade of high-mobility group box 1 (with glycyrrhizin) or interleukin-1β (with anakinra) did not prevent NETosis or protect against injury. Conclusions: NETosis was induced in VILI, and DNase treatment eliminated NETs. In contrast to experimental transfusion-related acute lung injury, NETs do not play a major pathogenic role in the current model of VILI.

scholarly journals Lung injury induced by short-term mechanical ventilation with hyperoxia and its mitigation by deferoxamine in rats

2020 ◽  
Author(s):  
Xiao-Xia Wang ◽  
Xiao-Lan Sha ◽  
Yulan Li ◽  
Chun-Lan Li ◽  
Su-Heng Chen ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Weight Ratio ◽  
Lavage Fluid ◽  
Tissue Homogenate ◽  
Short Term ◽  
Short Period ◽  
The Right

Abstract Backgroud Long-term mechanical ventilation with hyperoxia can induce lung injury.General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a very short period of time. It still remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia causes lung injury in rats and whether deferoxamine(DFO)could mitigate such injury to the lungs and explore the possible mechanism. Methods Twenty-four SD rats were randomly divided into 3 groups:mechanical ventilated with normoxia group (MV group, FiO2 =21%), with hyperoxia group(HMV group, FiO2 =90%), or with hyperoxia+DFO group(HMV+DFO group, FiO2 =90%). Mechanical ventilation under different oxygen concentrations was given for 4h. The HMV+DFO group received continuous intravenous infusion of DFO at 200mg•kg -1 •d -1 , while the MV and HMV groups received an equal volume of NS. Carotid artery intubation was carried out to monitor the blood gas parameters under mechanical ventilation for 2h and 4h, respectively, and the oxygenation index(OI) was calculated. After 4h ventilation, the right anterior lobe of the lung and bronchoalveolar lavage fluid from the right lung was sampled for pathological and biochemical assays. Results PaO2 in the HMV and HMV+DFO groups were significantly higher, but the OI were significantly lower than those of the MV group( p <0.01), while PaO2 and OI between HMV+DFO and HMV groups did not differ significantly. The lung pathological scores and the wet-to-dry weight ratio(W/D) in the HMV and HMV+DFO groups were significantly higher than those of the MV group, but score and the W/D were reduced by DFO( p <0.05,HMV+DFOvs.HMV). Biochemically, HMV resulted in significant reductions in SP-C, SP-D, and GR levels and elevation of XOD in both the Bronchoalveolar lavage fluid and the lung tissue homogenate, and all these changes were prevented or significantly reverted by DFO. Conclusions Mechanical ventilation with hyperoxia for 4h induced oxidative injury of the lungs, accompanied by a dramatic reduction in the concentrations of SP-C and SP-D. DFO could mitigate such injury by lowering XOD activity and elevating GR activity.

scholarly journals Treatment with senicapoc in a porcine model of acute respiratory distress syndrome

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Asbjørn G. Petersen ◽  
Peter C. Lind ◽  
Anne-Sophie B. Jensen ◽  
Mark A. Eggertsen ◽  
Asger Granfeldt ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Bronchoalveolar Lavage ◽  
Primary Endpoint ◽  
Bronchoalveolar Lavage Fluid ◽  
Distress Syndrome ◽  
Pulmonary Hemorrhage ◽  
Lavage Fluid

Abstract Background Senicapoc is a potent and selective blocker of KCa3.1, a calcium-activated potassium channel of intermediate conductance. In the present study, we investigated whether there is a beneficial effect of senicapoc in a large animal model of acute respiratory distress syndrome (ARDS). The primary end point was the PaO2/FiO2 ratio. Methods ARDS was induced in female pigs (42–49 kg) by repeated lung lavages followed by injurious mechanical ventilation. Animals were then randomly assigned to vehicle (n = 9) or intravenous senicapoc (10 mg, n = 9) and received lung-protective ventilation for 6 h. Results Final senicapoc plasma concentrations were 67 ± 18 nM (n = 9). Senicapoc failed to change the primary endpoint PaO2/FiO2 ratio (senicapoc, 133 ± 23 mmHg; vehicle, 149 ± 68 mmHg). Lung compliance remained similar in the two groups. Senicapoc reduced the level of white blood cells and neutrophils, while the proinflammatory cytokines TNFα, IL-1β, and IL-6 in the bronchoalveolar lavage fluid were unaltered 6 h after induction of the lung injury. Senicapoc-treatment reduced the level of neutrophils in the alveolar space but with no difference between groups in the cumulative lung injury score. Histological analysis of pulmonary hemorrhage indicated a positive effect of senicapoc on alveolar–capillary barrier function, but this was not supported by measurements of albumin content and total protein in the bronchoalveolar lavage fluid. Conclusions In summary, senicapoc failed to improve the primary endpoint PaO2/FiO2 ratio, but reduced pulmonary hemorrhage and the influx of neutrophils into the lung. These findings open the perspective that blocking KCa3.1 channels is a potential treatment to reduce alveolar neutrophil accumulation and improve long-term outcome in ARDS.

A rise of MMP-2 and MMP-9 in bronchoalveolar lavage fluid is associated with acute lung injury after cardiopulmonary bypass in a swine model

Perfusion ◽  
2003 ◽  
Vol 18 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Wolfgang Eichler ◽  
J F Matthias Bechtel ◽  
Jan Schumacher ◽  
Johanna A Wermelt ◽  
Karl-Friedrich Klotz ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Cardiopulmonary Bypass ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Swine Model ◽  
Tissue Samples ◽  
Pulmonary Capillary ◽  
A Prospective Study

Postoperative acute lung injury (ALI) contributes to the morbidity and mortality following cardiopulmonary bypass (CPB). To determine whether the presence of matrix metalloproteinases (MMPs) is associated with ALI after CPB, MMP-2 and MMP-9 activities in bronchoalveolar lavage fluid (BALF) were compared with parameters indicating impaired gas exchange. In a prospective study, 17 minipigs were subjected to CPB for 60 min. Before and at five and 180 min after CPB, MMP-2 and MMP-9 were assayed in BALF and the arterial-alveolar gradient of oxygen tension (AaDO2), the pulmonary capillary wedge pressure (PCWP) and the water content of lung tissue samples (Wt) were evaluated and compared with baseline values. MMP-2 and MMP-9 increased significantly 5 minutes (2.1- and 6.2-fold, respectively) and 180 minutes (3.4- and 14.3-fold, respectively) post-CPB. AaDO2 and Wt, but not PCWP, increased significantly 180 minutes after CPB and only AaDO2, but not PCWP or Wt, was significantly correlated with MMP-2 (r/0.66, p/0.006) and MMP-9 (r/0.62, p/0.01). In conclusion, high levels of MMP-2 and MMP-9 in the pulmonary compartment are associated with ALI after CPB.

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