Proteoglycan fragmentation and respiratory mechanics in mechanically ventilated healthy rats

2007 ◽  
Vol 103 (3) ◽  
pp. 747-756 ◽  
Author(s):  
Andrea Moriondo ◽  
Paolo Pelosi ◽  
Alberto Passi ◽  
Manuela Viola ◽  
Cristiana Marcozzi ◽  
...  
Keyword(s):  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Respiratory Mechanics ◽  
Minute Ventilation ◽  
Lung Parenchyma ◽  
Matrix Metalloproteinase 2 ◽  
Clinical Tool ◽  
Lung Water ◽  
Mechanically Ventilated ◽  
Spontaneously Breathing

This research investigated whether stretching of lung tissue due to increased positive alveolar pressure swings during mechanical ventilation (MV) at various tidal volumes (Vt) might affect the composition and/or structure of the glycosaminoglycan (GAG) components of pulmonary extracellular proteoglycans. Experiments were performed in 30 healthy rats: 1) anesthetized and immediately killed (controls, C-0); 2) anesthetized and spontaneously breathing for 4 h (C-4h); and 3) anesthetized, paralyzed, and mechanically ventilated for 4 h with air at 0-cmH2O end-expiratory pressure and Vt of 8 ml/kg (MV-1), 16 ml/kg (MV-2), 24 ml/kg (MV-3), or 32 ml/kg (MV-4), adjusting respiratory rates at a minute ventilation of 270 ml/min. Compared with C-0 and C-4h, a significant reduction of dynamic and static compliance of the respiratory system and of the lung was observed only in MV-4, while extravascular lung water significantly increased in MV-3 and MV-4, but not in MV-1 and MV-2. However, even in MV-1, MV induced a significant fragmentation of pulmonary GAGs. Extraction of covalently bound GAGs and wash out of loosely bound or fragmented GAGs progressively increased with increasing Vt and was associated with increased expression of local (matrix metalloproteinase-2) and systemic (matrix metalloproteinase-9) activated metalloproteases. We conclude that 1) MV, even at “physiological” low Vt, severely affects the pulmonary extracellular architecture, exposing the lung parenchyma to development of ventilator-induced lung injury; and 2) respiratory mechanics is not a reliable clinical tool for early detection of lung injury.

scholarly journals Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Binbin Zheng ◽  
Hongbo Yang ◽  
Jianan Zhang ◽  
Xueli Wang ◽  
Hao Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Neutrophil Infiltration ◽  
Negative Regulator ◽  
Matrix Metalloproteinase 2 ◽  
Cytokine Signaling

Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.

scholarly journals Derecruitment Test and Surfactant Therapy in Patients with Acute Lung Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Alexey A. Smetkin ◽  
Vsevolod V. Kuzkov ◽  
Konstantin M. Gaidukov ◽  
Lars J. Bjertnaes ◽  
Mikhail Y. Kirov
Keyword(s):  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Predictive Value ◽  
Conventional Therapy ◽  
Therapy Group ◽  
Lung Mechanics ◽  
Lung Water ◽  
Mechanically Ventilated ◽  
Water Index

Introduction. A recruitment maneuver (RM) may improve gas exchange in acute lung injury (ALI). The aim of our study was to assess the predictive value of a derecruitment test in relation to RM and to evaluate the efficacy of RM combined with surfactant instillation in patients with ALI.Materials and Methods. Thirteen adult mechanically ventilated patients with ALI were enrolled into a prospective pilot study. The patients received protective ventilation and underwent RM followed by a derecruitment test. After a repeat RM, bovine surfactant (surfactant group,n=6) or vehicle only (conventional therapy group,n=7) was instilled endobronchially. We registered respiratory and hemodynamic parameters, including extravascular lung water index (EVLWI).Results. The derecruitment test decreased the oxygenation in 62% of the patients. We found no significant correlation between the responses to the RM and to the derecruitment tests. The baseline EVLWI correlated with changes in SpO2following the derecruitment test. The surfactant did not affect gas exchange and lung mechanics but increased EVLWI at 24 and 32 hrs.Conclusions. Our study demonstrated no predictive value of the derecruitment test regarding the effects of RM. Surfactant instillation was not superior to conventional therapy and might even promote pulmonary edema in ALI.

Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury

2006 ◽  
Vol 100 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Flavia B. Santos ◽  
Lilian K. S. Nagato ◽  
Nicolau M. Boechem ◽  
Elnara M. Negri ◽  
Alberto Guimarães ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Time Course ◽  
Collagen Fiber ◽  
Lung Parenchyma ◽  
Collagen Fibers ◽  
Type Iii Collagen ◽  
Type Iii ◽  
Metalloproteinase 9

The aim of this study is to test the hypothesis that the early changes in lung mechanics and the amount of type III collagen fiber do not predict the evolution of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury (ALI). For this purpose, we analyzed the time course of lung parenchyma remodeling in murine models of pulmonary and extrapulmonary ALI with similar degrees of mechanical compromise at the early phase of ALI. Lung histology (light and electron microscopy), the amount of elastic and collagen fibers in the alveolar septa, the expression of matrix metalloproteinase-9, and mechanical parameters (lung-resistive and viscoelastic pressures, and static elastance) were analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C) pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it; 0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10 μg it and 125 μg ip, respectively). At 24 h, all mechanical and morphometrical parameters, as well as type III collagen fiber content, increased similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological data returned to control values at 1 wk. However, in ALIp, static elastance returned to control values at 3 wk, whereas resistive and viscoelastic pressures, as well as type III collagen fibers and elastin, remained elevated until week 8. ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas mice with ALI induced by endothelial lesion developed only fibrosis that was repaired early in the course of lung injury. Furthermore, early functional and morphological changes did not predict lung parenchyma remodeling.

scholarly journals Dexamethasone Ameliorates H2S-Induced Acute Lung Injury by Alleviating Matrix Metalloproteinase-2 and -9 Expression

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94701 ◽  
Author(s):  
Jun Wang ◽  
Huazhong Zhang ◽  
Chenglei Su ◽  
Junjie Chen ◽  
Baoli Zhu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2

scholarly journals CXCR4 regulates migration of lung alveolar epithelial cells through activation of Rac1 and matrix metalloproteinase-2

2012 ◽  
Vol 302 (9) ◽  
pp. L846-L856 ◽  
Author(s):  
Manik C. Ghosh ◽  
Patrudu S. Makena ◽  
Vijay Gorantla ◽  
Scott E. Sinclair ◽  
Christopher M. Waters
Keyword(s):  
Cell Migration ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Chemokine Receptor ◽  
Matrix Metalloproteinase 2 ◽  
Alveolar Type ◽  
Type I ◽  
Epithelial Repair ◽  
Alveolar Epithelial

Restoration of the epithelial barrier following acute lung injury is critical for recovery of lung homeostasis. After injury, alveolar type II epithelial (ATII) cells spread and migrate to cover the denuded surface and, eventually, proliferate and differentiate into type I cells. The chemokine CXCL12, also known as stromal cell-derived factor 1α, has well-recognized roles in organogenesis, hematopoiesis, and immune responses through its binding to the chemokine receptor CXCR4. While CXCL12/CXCR4 signaling is known to be important in immune cell migration, the role of this chemokine-receptor interaction has not been studied in alveolar epithelial repair mechanisms. In this study, we demonstrated that secretion of CXCL12 was increased in the bronchoalveolar lavage of rats ventilated with an injurious tidal volume (25 ml/kg). We also found that CXCL12 secretion was increased by primary rat ATII cells and a mouse alveolar epithelial (MLE12) cell line following scratch wounding and that both types of cells express CXCR4. CXCL12 significantly increased ATII cell migration in a scratch-wound assay. When we treated cells with a specific antagonist for CXCR4, AMD-3100, cell migration was significantly inhibited. Knockdown of CXCR4 by short hairpin RNA (shRNA) caused decreased cell migration compared with cells expressing a nonspecific shRNA. Treatment with AMD-3100 decreased matrix metalloproteinase-14 expression, increased tissue inhibitor of metalloproteinase-3 expression, decreased matrix metalloproteinase-2 activity, and prevented CXCL12-induced Rac1 activation. Similar results were obtained with shRNA knockdown of CXCR4. These findings may help identify a therapeutic target for augmenting epithelial repair following acute lung injury.

Ethane production rates and minute ventilation

1989 ◽  
Vol 66 (3) ◽  
pp. 1264-1267 ◽  
Author(s):  
M. P. Habib ◽  
M. A. Katz
Keyword(s):  
Minute Ventilation ◽  
Arterial Line ◽  
Air Breathing ◽  
Mechanically Ventilated ◽  
Lack Of Control ◽  
Ethane Production ◽  
Poorly Soluble ◽  
The Mean ◽  
Spontaneously Breathing ◽  
Free Radical Activity

Ethane quantitated in the expired alveolar gas is a noninvasive measure of free radical activity. This method has been criticized for lack of control of minute ventilation (VE) in spontaneously breathing animals, although ethane, which is poorly soluble in tissues, should not be affected by changes in VE. We measured ethane elimination rates in six strain 13 guinea pigs (GP13) during spontaneous room air breathing and in six room air breathing, pentobarbital-anesthetized, tracheostomized, externally warmed, mechanically ventilated GP13s at various levels of VE. In the ventilated animals, weight0.75/VE (metabolic activity corrected for VE) was a linear function of arterial CO2 tension (PaCO2) drawn from arterial line (r = 0.72, P less than 0.005). However, weight0.75/VE did not correlate with ethane elimination rates (r = 0.12, not significant). The mean (+/- SD) ethane elimination rates in the spontaneously breathing animals was 3.15 +/- 0.96 pmol.min-1.100 g-1 and was not significantly different from the mean rate in the mechanically ventilated animals (3.11 +/- 1.37) over a range of VE's. These data demonstrate that ethane elimination rates are not affected by changes in VE and are unaffected by pentobarbital anesthesia.

Effects of lung injury on pulmonary surfactant aggregate conversion in vivo and in vitro

1997 ◽  
Vol 272 (5) ◽  
pp. L872-L878 ◽  
Author(s):  
R. A. Veldhuizen ◽  
Y. Ito ◽  
J. Marcou ◽  
L. J. Yao ◽  
L. McCaig ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Surface Area ◽  
Pulmonary Surfactant ◽  
Breathing Pattern ◽  
Mechanically Ventilated ◽  
Surface Active ◽  
Spontaneously Breathing

Within the alveolar space pulmonary surfactant is converted from the surface active large aggregates (LA) to the inactive small aggregates (SA). This conversion is affected by a change in surface area, lung injury, breathing pattern, and protease activity. This study examined the effect of N-nitroso-N-methylurethane-induced acute lung injury on aggregate conversion in mechanically ventilated and spontaneously breathing rabbits. Both the in vitro surface area cycling techniques and the in vivo technique of intratracheally injecting radiolabeled LA were used for analyzing aggregate conversion. Mechanical ventilation of injured lungs resulted in increased aggregate conversion and increased surfactant aggregate ratios compared with controls. Spontaneously breathing injured animals had aggregate conversion and aggregate ratios that were not significantly different from controls. In vitro aggregate conversion was slower for LA obtained from injured animals compared with normal animals. We conclude that the mechanical stress of mechanical ventilation results in increased aggregate conversion and aggregate ratios. Furthermore, in vitro conversion of isolated LA does not necessarily reflect the conversion of aggregates within the alveoli.

scholarly journals Imaging atelectrauma in Ventilator-Induced Lung Injury using 4D X-ray microscopy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luca Fardin ◽  
Ludovic Broche ◽  
Goran Lovric ◽  
Alberto Mittone ◽  
Olivier Stephanov ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Lung Parenchyma ◽  
Contrast Imaging ◽  
Barrier Dysfunction ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Regional Lung ◽  
Ventilation Strategies ◽  
Protective Mechanical Ventilation

AbstractMechanical ventilation can damage the lungs, a condition called Ventilator-Induced Lung Injury (VILI). However, the mechanisms leading to VILI at the microscopic scale remain poorly understood. Here we investigated the within-tidal dynamics of cyclic recruitment/derecruitment (R/D) using synchrotron radiation phase-contrast imaging (PCI), and the relation between R/D and cell infiltration, in a model of Acute Respiratory Distress Syndrome in 6 anaesthetized and mechanically ventilated New-Zealand White rabbits. Dynamic PCI was performed at 22.6 µm voxel size, under protective mechanical ventilation [tidal volume: 6 ml/kg; positive end-expiratory pressure (PEEP): 5 cmH2O]. Videos and quantitative maps of within-tidal R/D showed that injury propagated outwards from non-aerated regions towards adjacent regions where cyclic R/D was present. R/D of peripheral airspaces was both pressure and time-dependent, occurring throughout the respiratory cycle with significant scatter of opening/closing pressures. There was a significant association between R/D and regional lung cellular infiltration (p = 0.04) suggesting that tidal R/D of the lung parenchyma may contribute to regional lung inflammation or capillary-alveolar barrier dysfunction and to the progression of lung injury. PEEP may not fully mitigate this phenomenon even at high levels. Ventilation strategies utilizing the time-dependence of R/D may be helpful in reducing R/D and associated injury.

Sign in / Sign up

Export Citation Format

Share Document