Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits

2005 ◽  
Vol 99 (2) ◽  
pp. 433-444 ◽  
Author(s):  
Edgardo D'Angelo ◽  
Matteo Pecchiari ◽  
Patrizia Della Valle ◽  
Antonia Koutsoukou ◽  
Joseph Milic-Emili
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Albumin Concentration ◽  
Open Chest ◽  
Interstitial Pulmonary Edema ◽  
Tnf Α ◽  
Low Volume

Lung mechanics, exhaled NO (NOe), and TNF-α in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3–4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (−42 and −25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (−25 and −20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-α was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-α levels.

scholarly journals 2045 The role of TGFβ in driving early cystic fibrosis lung disease

2018 ◽  
Vol 2 (S1) ◽  
pp. 33-33
Author(s):  
Elizabeth L. Kramer ◽  
William Hardie ◽  
Kristin Hudock ◽  
Cynthia Davidson ◽  
Alicia Ostmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Bronchoalveolar Lavage Fluid ◽  
Transforming Growth Factor ◽  
Genetic Modifier ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Patient Specific

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.

Conventional Mechanical Ventilation Is Associated with Bronchoalveolar Lavage-induced Activation of Polymorphonuclear Leukocytes

2002 ◽  
Vol 97 (6) ◽  
pp. 1426-1433 ◽  
Author(s):  
Haibo Zhang ◽  
Gregory P. Downey ◽  
Peter M. Suter ◽  
Arthur S. Slutsky ◽  
V. Marco Ranieri
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Polymorphonuclear Leukocytes ◽  
Bronchoalveolar Lavage Fluid ◽  
Distress Syndrome ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Multiple Organ ◽  
Protective Strategy ◽  
Oxidant Production

Background Protective ventilatory strategies have resulted in a decreased mortality rate in acute respiratory distress syndrome, but the underlying mechanisms remain unclear. The authors hypothesized that (1) mechanical ventilation modulates activation of polymorphonuclear leukocytes (PMNs), (2) the consequent release of proteinases is correlated with a systemic inflammatory response and with multiple organ dysfunction, and (3) these deleterious effects can be minimized by a protective ventilatory strategy. Methods Human PMNs were incubated with bronchoalveolar lavage fluid obtained from patients at entry or 36 h after randomization to ventilation with either a conventional (control) or a lung-protective strategy. PMN oxidant production and surface expression of adhesion molecules and granule markers, including CD18, CD63, and L-selectin, were measured by flow cytometry. Extracellular elastase activity was quantified using a fluorescent substrate. Results Bronchoalveolar lavage obtained from both groups of patients at entry showed similar effects on PMN oxidant production and expression of surface markers. At 36 h, exposure of PMNs to bronchoalveolar lavage fluid from the control group resulted in increased PMN activation as manifested by a significant increase in oxidant production, CD18, and CD63 surface expression, and shedding of L-selectin. By contrast, these variables were unchanged at 36 h in the lung-protective group. There was a significant correlation between the changes of the variables and changes in interleukin-6 level and the number of failing organs. Conclusions Polymorphonuclear leukocytes can be activated by mechanical ventilation, and the consequent release of elastase was correlated with the degree of systemic inflammatory response and multiple organ failure. This result may possibly explain the decreased mortality in acute respiratory distress syndrome patients treated with a lung-protective strategy.

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 Orotracheal treprostinil administration attenuates bleomycin-induced lung injury, vascular remodeling, and fibrosis in mice

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401988195
Author(s):  
Ioanna Nikitopoulou ◽  
Nikolaos Manitsopoulos ◽  
Anastasia Kotanidou ◽  
Xia Tian ◽  
Aleksandar Petrovic ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Vascular Remodeling ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Lung Pathology ◽  
Prostacyclin Analogue

Pulmonary fibrosis is a progressive disease characterized by disruption of lung architecture and deregulation of the pulmonary function. Prostacyclin, a metabolite of arachidonic acid, is a potential disease mediator since it exerts anti-inflammatory and anti-fibrotic actions. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycin-induced experimental pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice ( n = 9–10/group) at day 0. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Evaluation of lung pathology was performed in tissue samples and bronchoalveolar lavage fluid collected 7, 14 and 21 days after bleomycin exposure. Lung injury was achieved due to bleomycin exposure at all time points as indicated by impaired lung mechanics, pathologic lung architecture (from day 14), and cellular and protein accumulation in the alveolar space accompanied by a minor decrease in lung tissue VE-cadherin at day 14. Treprostinil preserved lung mechanics, and reduced lung inflammation, fibrosis, and vascular remodeling (day 21); reduced cellularity and protein content of bronchoalveolar lavage fluid were additionally observed with no significant effect on VE-cadherin expression. Bleomycin-induced collagen deposition was attenuated by treprostinil from day 14, while treprostinil involvement in regulating inflammatory processes appears mediated by NF-κB signaling. Overall, prophylactic administration of treprostinil, a stable prostacyclin analogue, maintained lung function, and prevented bleomycin-induced lung injury, and fibrosis, as well as vascular remodeling, a hallmark of pulmonary hypertension. This suggests potential therapeutic efficacy of treprostinil in pulmonary fibrosis and possibly in pulmonary hypertension related to chronic lung diseases.

scholarly journals TGF-β1, IL-6 and TNF-α in Bronchoalveolar Lavage Fluid: Useful Markers for Lung Cancer?

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Zhongbo Chen ◽  
Zhiwei Xu ◽  
Shifang Sun ◽  
Yiming Yu ◽  
Dan Lv ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Tnf Α ◽  
Tgf Β1

scholarly journals Sigh maneuver protects healthy lungs during mechanical ventilation in adult Wistar rats

2020 ◽  
Vol 245 (15) ◽  
pp. 1404-1413
Author(s):  
Andréa Cristiane Lopes da Silva ◽  
Natália Alves de Matos ◽  
Ana Beatriz Farias de Souza ◽  
Thalles de Freitas Castro ◽  
Leandro da Silva Cândido ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Partial Pressure ◽  
Wistar Rats ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Protective Role ◽  
Arterial Blood

Mechanical ventilation (MV) is a tool used for the treatment of patients with acute or chronic respiratory failure. However, MV is a non-physiological resource, and it can cause metabolic disorders such as release of pro-inflammatory cytokines and production of reactive oxygen species. In clinical setting, maneuvers such as sigh, are used to protect the lungs. Thus, this study aimed to evaluate the effects of sigh on oxidative stress and lung inflammation in healthy adult Wistar rats submitted to MV. Male Wistar rats were divided into four groups: control (CG), mechanical ventilation (MVG), MV set at 20 sighs/h (MVG20), and MV set at 40 sighs/h (MVG40). The MVG, MVG20, and MVG40 were submitted to MV for 1 h. After the protocol, all animals were euthanized and the blood, bronchoalveolar lavage fluid, and lungs were collected for subsequent analysis. In the arterial blood, MVG40 presented higher partial pressure of oxygen and lower partial pressure of carbon dioxide compared to control. The levels of bicarbonate in MVG20 were lower compared to CG. The neutrophil influx in bronchoalveolar lavage fluid was higher in the MVG compared to CG and MVG40. In the lung parenchyma, the lipid peroxidation was higher in MVG compared to CG, MVG20, and MVG40. Superoxide dismutase and catalase activity were higher in MVG compared to CG, MVG20, and MVG40. The levels of IL-1, IL-6, and TNF in the lung homogenate were higher in MVG compared to CG, MVG20, and MVG40. The use of sigh plays a protective role as it reduced redox imbalance and pulmonary inflammation caused by MV.

Characterization of LPS-induced lung inflammation incftr−/−mice and the effect of docosahexaenoic acid

2002 ◽  
Vol 92 (5) ◽  
pp. 2169-2176 ◽  
Author(s):  
Steven D. Freedman ◽  
Deborah Weinstein ◽  
Paola G. Blanco ◽  
Pedro Martinez-Clark ◽  
Serge Urman ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Membrane Lipid ◽  
Inflammatory Parameters ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Factor Α

The mechanism by which Pseudomonas causes excessive inflammation in the cystic fibrosis lung is unclear. We have reported that arachidonic acid is increased and docosahexaenoic acid (DHA) decreased in lung, pancreas, and ileum from cftr−/−mice. Oral DHA corrected this defect and reversed the pathology. To determine which mediators regulate inflammation in lungs from cftr−/−mice and whether inhibition occurs with DHA, cftr−/−and wild-type (WT) mice were exposed to aerosolized Pseudomonas lipopolysaccharide (LPS). After 2 days of LPS, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2, and KC levels in bronchoalveolar lavage fluid were increased in cftr−/−compared with WT mice and not suppressed by pretreatment with oral DHA. Neutrophil levels were not different between cftr−/−and WT mice. After 3 days of aerosolized LPS, neutrophil concentration, TNF-α, and the eicosanoids 6-keto-PGF1α, PGF2α, PGE2, and thromboxane B2were all increased in bronchoalveolar lavage fluid from cftr−/−mice compared with WT controls. Oral DHA had no significant effect on TNF-α levels in cftr−/−mice. In contrast, neutrophils and eicosanoids were decreased in cftr−/−but not in WT mice treated with DHA, indicating that the effects of DHA on these inflammatory parameters may be related to correction of the membrane lipid defect.

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