scholarly journals Pre-treatment with Isoflurane or Sevoflurane is not protective against high tidal volume induced lung injury in rats

2019 ◽  
Author(s):  
Florian Setzer ◽  
Lars Hueter ◽  
Barbara Schmidt ◽  
Konrad Schwarzkopf ◽  
Torsten Schreiber
Keyword(s):  
Mechanical Ventilation ◽  
Body Weight ◽  
Lung Injury ◽  
Tidal Volume ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Protective Effects ◽  
Markers Of Inflammation ◽  
In Vivo Animal Model

Abstract Background Volatile anesthetics (VA) may exert organ-protective effects in various experimental and clinical settings. Mechanical ventilation (MV) induces an inflammatory response and, depending on the ventilator settings chosen, injury in the lungs. It is unclear if prophylactic inhaled VA applied on healthy lungs prior to MV are protective regarding these effects.Methods Healthy, spontaneously breathing rats were exposed for 30 minutes to either isoflurane (1.8 Vol %), sevoflurane (3.0 Vol %) or no VA (controls). Animals were allowed to recover and then mechanically ventilated for 4 hours with either high (21 ml/kg body weight) or low (9 ml/kg body weight) tidal volume. Cardiorespiratory parameters and systemic inflammation were assessed at the beginning and during mechanical ventilation. Cellular, non-cellular and histologic markers of pulmonary injury and inflammation were determined.Results Irrespective of VA pretreatment, MV with high VT negatively affected markers of lung integrity such as arterial oxygenation and lung wet-to-dry ratio. Regarding the application of VA pretreatment protective effects on lung function were absent but there were changes in some markers of inflammation such as a decrease in blood lymphocyte counts and an increase in interleukin 6 concentration in plasma and in lung lavage fluid. These effects were heterogeneous regarding group allocation and time points.Conclusions In this in in vivo animal model, prophylactic administration of inhaled VA was not beneficial or protective regarding ventilation induced lung injury. However, there were effects suggestive of a modulation of inflammatory markers associated with VA prophylaxis. The clinical or biological relevance of these findings so far remain unclear and should be subject to further studies.

scholarly journals A single, 30 minutes pretreatment with Isoflurane or Sevoflurane is not protective against high tidal volume induced lung injury in rats

2020 ◽  
Author(s):  
Florian Setzer ◽  
Lars Hueter ◽  
Barbara Schmidt ◽  
Konrad Schwarzkopf ◽  
Torsten Schreiber
Keyword(s):  
Mechanical Ventilation ◽  
Body Weight ◽  
Lung Injury ◽  
Tidal Volume ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Protective Effects ◽  
Markers Of Inflammation ◽  
In Vivo Animal Model

Abstract Background: Volatile anesthetics (VA) may exert organ-protective effects in various experimental and clinical settings. Mechanical ventilation (MV) induces an inflammatory response and, depending on the ventilator settings chosen, injury in the lungs. It is unclear if prophylactic inhaled VA applied on healthy lungs prior to MV are protective regarding these effects. Methods: Healthy, spontaneously breathing rats were exposed for 30 minutes to either isoflurane (1.8 Vol %), sevoflurane (3.0 Vol %) or no VA. Animals were allowed to recover, intraperitoneally anesthetized and then mechanically ventilated for 4 hours with either high (21 ml/kg body weight) or low (9 ml/kg body weight) tidal volume (n = 12 per group). Cardiorespiratory parameters and systemic inflammation were assessed at the beginning and during mechanical ventilation. Cellular, non-cellular and histologic markers of pulmonary injury and inflammation were determined. Results: Irrespective of VA pretreatment, MV with high VT negatively affected markers of lung integrity such as arterial oxygenation and lung wet-to-dry ratio. Following VA pretreatment we found no protective effects on lung function but there were changes in some markers of inflammation such as a decrease in blood lymphocyte counts and an increase in interleukin 6 concentration in plasma and lung lavage fluid. These effects were heterogeneous regarding group allocation and time points. Conclusions: In this in in vivo animal model, prophylactic administration of inhaled VA was not beneficial or protective regarding ventilation induced lung injury. However, there were effects suggestive of a modulation of inflammatory markers associated with VA prophylaxis. The clinical or biological relevance of these findings so far remain unclear and should be subject to further studies.

scholarly journals High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury

2003 ◽  
Vol 95 (4) ◽  
pp. 1385-1393 ◽  
Author(s):  
Michael R. Wilson ◽  
Sharmila Choudhury ◽  
Michael E. Goddard ◽  
Kieran P. O'Dea ◽  
Andrew G. Nicholson ◽  
...  
Keyword(s):  
Lung Injury ◽  
Mouse Model ◽  
Tidal Volume ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
High Tidal Volume ◽  
Lung Pathology ◽  
Ventilator Induced Lung Injury ◽  
Tnf Α

Mechanical ventilation has been demonstrated to exacerbate lung injury, and a sufficiently high tidal volume can induce injury in otherwise healthy lungs. However, it remains controversial whether injurious ventilation per se, without preceding lung injury, can initiate cytokine-mediated pulmonary inflammation. To address this, we developed an in vivo mouse model of acute lung injury produced by high tidal volume (Vt) ventilation. Anesthetized C57BL6 mice were ventilated at high Vt (34.5 ± 2.9 ml/kg, mean ± SD) for a duration of 156 ± 17 min until mean blood pressure fell below 45 mmHg ( series 1); high Vt for 120 min ( series 2); or low Vt (8.8 ± 0.5 ml/kg) for 120 or 180 min ( series 3). High Vt produced progressive lung injury with a decrease in respiratory system compliance, increase in protein concentration in lung lavage fluid, and lung pathology showing hyaline membrane formation. High-Vt ventilation was associated with increased TNF-α in lung lavage fluid at the early stage of injury ( series 2) but not the later stage ( series 1). In contrast, lavage fluid macrophage inflammatory protein-2 (MIP-2) was increased in all high-Vt animals. Lavage fluid from high-Vt animals contained bioactive TNF-α by WEHI bioassay. Low-Vt ventilation induced minimal changes in physiology and pathology with negligible TNF-α and MIP-2 proteins and TNF-α bioactivity. These results demonstrate that high-Vt ventilation in the absence of underlying injury induces intrapulmonary TNF-α and MIP-2 expression in mice. The apparently transient nature of TNF-α upregulation may help explain previous controversy regarding the involvement of cytokines in ventilator-induced lung injury.

scholarly journals Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model

2009 ◽  
Vol 296 (1) ◽  
pp. L3-L11 ◽  
Author(s):  
Jeffrey M. Dodd-o ◽  
Maria Hristopoulos ◽  
Daniel Scharfstein ◽  
Roy Brower ◽  
Paul Hassoun ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Kidney Injury ◽  
Interactive Effects ◽  
Blue Dye ◽  
Ventilatory Mode ◽  
Lung Trauma ◽  
Kidney Health

We hypothesized that the influence of acute kidney injury (AKI) on the sensitivity of the lung to an injurious process varies with the severity of the injurious process. Thus, we thought that AKI would exacerbate lung injury from low degrees of lung trauma but attenuate lung injury from higher degrees of lung trauma. C57BL/6 mice underwent AKI (30-min kidney ischemia) or sham surgery, followed at 24 h by 4 h of spontaneous breathing (SB), mechanical ventilation with low tidal volume (7 ml/kg, LTV), or mechanical ventilation with high tidal volume (30 ml/kg, HTV). Compared with LTV, median bronchoalveolar lavage (BAL) protein leak was significantly lower with SB and greater with HTV in both sham and AKI mice. Compared with LTV, median Evans blue dye-labeled albumin extravasation in lungs (L-EBD) was also significantly lower with SB and greater with HTV. L-EBD showed a significant interaction between ventilatory mode and kidney health, such that AKI attenuated the L-EBD rise seen in HTV vs. LTV sham mice. An interaction between ventilatory mode and kidney health could also be seen in BAL neutrophil number (PMN). Thus, AKI attenuated the BAL PMN rise seen in HTV vs. LTV sham mice. These data support the presence of a complex interaction between mechanical ventilation and AKI in which the sensitivity of the lung to trauma varies with the magnitude of the trauma and may involve a modification of pulmonary neutrophil activity by AKI.

Prevention of thiourea-induced pulmonary edema by hydroxyl-radical scavengers

1983 ◽  
Vol 55 (5) ◽  
pp. 1456-1459 ◽  
Author(s):  
R. B. Fox ◽  
R. N. Harada ◽  
R. M. Tate ◽  
J. E. Repine
Keyword(s):  
Body Weight ◽  
Lung Injury ◽  
Hydroxyl Radical ◽  
Pulmonary Edema ◽  
Lung Lavage ◽  
Radical Scavengers ◽  
Lung Weight ◽  
Hydroxyl Radical Scavengers ◽  
Mediated Oxidation

Thiourea (TU), a very effective hydroxyl radical (.OH) scavenger, has little value as a probe of .OH in vivo because it causes fatal pulmonary edema. To test the hypothesis that TU-induced lung injury results from .OH-mediated oxidation of TU to toxic cyanamide, we pretreated rats with .OH scavengers, dimethylsulfoxide (DMSO), ethanol, and mannitol, prior to treatment with TU (3 mg/kg), preventing 91, 63, and 53%, respectively, of increases in lung weight to body weight ratios and 93, 67, and 46% of increases in lung lavage albumin concentrations. Furthermore, treatment of rats with cyanamide (CYN) (100 mg/kg) also caused increases in lung weight to body weight ratios (CYN: 7.39 +/- 0.57 X 10(-3) vs. controls: 5.46 +/- 0.26). N,N′-dimethylation of TU (DMTU) prevented TU toxicity, because treatment with DMTU did not significantly increase lung weight to body weight ratios (DMTU: 5.12 +/- 0.16 X 10(-3) vs. controls: 5.46 +/- 0.26) or lung lavage albumin (DMTU: 14 +/- 1 mg/100 ml vs. controls: 11 +/- 1). DMTU remained a very effective in vivo .OH scavenger, increasing survival of lethally irradiated mice treated with 600 mg/kg DMTU to 79% compared with 8% in untreated controls.

scholarly journals Sources of alveolar soluble TNF receptors during acute lung injury of different etiologies

2011 ◽  
Vol 111 (1) ◽  
pp. 177-184 ◽  
Author(s):  
Anthony D. Dorr ◽  
Michael R. Wilson ◽  
Kenji Wakabayashi ◽  
Alicia C. Waite ◽  
Brijesh V. Patel ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophage ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Epithelial Permeability ◽  
Alveolar Epithelial ◽  
Factor Α

Elevated soluble tumor necrosis factor-α receptor (sTNFR) levels in bronchoalveolar lavage fluid (BALF) are associated with poor patient outcome in acute lung injury (ALI). The mechanisms underlying these increases are unknown, but it is possible that pulmonary inflammation and increased alveolar epithelial permeability may individually contribute. We investigated mechanisms of elevated BALF sTNFRs in two in vivo mouse models of ALI. Anesthetized mice were challenged with intratracheal lipopolysaccharide or subjected to injurious mechanical ventilation. Lipopolysaccharide instillation produced acute intra-alveolar inflammation, but minimal alveolar epithelial permeability changes, with increased BALF sTNFR p75, but not p55. Increased p75 levels were markedly attenuated by alveolar macrophage depletion. In contrast, injurious ventilation induced substantial alveolar epithelial permeability, with increased BALF p75 and p55, which strongly correlated with total protein. BALF sTNFRs were not increased in isolated buffer-perfused lungs (devoid of circulating sTNFRs) subjected to injurious ventilation. These results suggest that lipopolysaccharide-induced intra-alveolar inflammation upregulates alveolar macrophage-mediated production of sTNFR p75, whereas enhanced alveolar epithelial permeability following mechanical ventilation leads to increased BALF p75 and p55 via plasma leakage. These data provide new insights into differential regulation of intra-alveolar sTNFR levels during ALI and may suggest sTNFRs as potential markers for evaluating the pathophysiology of ALI.

scholarly journals Mechanical ventilation of rat lung: effect on surfactant forms

1999 ◽  
Vol 277 (2) ◽  
pp. L320-L326 ◽  
Author(s):  
Jordan Savov ◽  
R. Silbajoris ◽  
S. L. Young
Keyword(s):  
Mechanical Ventilation ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Ventilation Pattern ◽  
Ventilation Strategies ◽  
Morphological Transformations ◽  
Profile Area

Mechanical ventilation of the lung could affect surfactant turnover by alteration of its secretion, recycling, and degradation. In vitro studies of surfactant subfractions recoverable from lavage fluid have led to predictions about surfactant physiology in vivo that include morphological transformations. We used electron microscopy to study in situ lipid forms in alveoli of rat lungs after two ventilation strategies [15 min at pressures (cmH2O) of 20/0 or 20/10]. In control animals, 4% of the lipid profile area in the surface lining layer was myelin figures (MF), 14% was tubular myelin, 37% was vesicular forms (VF), and the remainder (45%) was hypophase. Compared with controls, the length-normalized sum of the lipid forms and the hypophase was two times as great in the lungs of the 20/0 group. MF were threefold higher in the 20/0 group and fivefold higher in the 20/10 group. VF doubled after ventilation at 20/0, but VF were the same as control after ventilation at 20/10. The results showed that a ventilation pattern of 20/0 compared with that of 20/10 group was associated with a significantly larger VF, suggesting an increased net production of these surfactant forms during a large tidal volume breathing pattern. These morphological results are consistent with published results using physical methods of fractionating lung lavage.

scholarly journals Accurate Tidal Volume for Patients under Mechanical Ventilation: A Cross-sectional Descriptive Study

2020 ◽  
Author(s):  
Leila Sayadi ◽  
Shahrzad Ghiyasvandian ◽  
Ali Karimi Rozveh ◽  
Samira Norouzrajabi
Keyword(s):  
Mechanical Ventilation ◽  
Body Weight ◽  
Lung Injury ◽  
Tidal Volume ◽  
Improve Patient Safety ◽  
Descriptive Study ◽  
Predicted Body Weight ◽  
Volume Determination ◽  
Cross Sectional ◽  
Nurses Knowledge

Background: In order to prevent lung injury among patients under mechanical ventilation, tidal volume should be determined based on predicted body weight. The aim of the study was to determine the accuracy of tidal volume determination for patients under mechanical ventilation and to assess nurses’ knowledge about accurate tidal volume determination. Methods: This was a cross-sectional descriptive study. This study was conducted on 250 patients under mechanical ventilation and 75 nurses who provided care to the patients. Patients’ height was estimated based on their ulna length and then, their predicted body weight and tidal volume were estimated. Nurses’ knowledge about tidal volume determination was also assessed. Results: The mean of delivered tidal volume was 9.1±1.73 mL/kg of predicted body weight. Tidal volume for 172 patients (68.8%) had been set at more than 8 mL/kg of predicted body weight. Forty nine nurses (65.3%) noted that there was no guideline in their wards for height and weight measurement. They determined patients’ weight and height through either visual estimation (21 nurses; 28.0%) or asking from their colleagues, patients, or patients’ family members (48 nurses; 64.0%). Conclusion: Nurses have limited knowledge about accurate tidal volume determination and hence, deliver high tidal volume to patients under mechanical ventilation which puts them at risk for ventilator-associated lung injury. Urgent interventions such as lung-protective strategies, staff training, and careful managerial supervision are needed to prevent ventilator-associated lung injury and improve patient safety.

scholarly journals Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch

2019 ◽  
Vol 30 (8) ◽  
pp. 959-974 ◽  
Author(s):  
Yunbo Ke ◽  
Pratap Karki ◽  
Chenou Zhang ◽  
Yue Li ◽  
Trang Nguyen ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Endothelial Cell ◽  
Lung Injury ◽  
Tidal Volume ◽  
Small Gtpase ◽  
Cyclic Stretch ◽  
Cell Junctions ◽  
Protective Effects ◽  
Barrier Dysfunction

Mechanical ventilation remains an imperative treatment for the patients with acute respiratory distress syndrome, but can also exacerbate lung injury. We have previously described a key role of RhoA GTPase in high cyclic stretch (CS)–induced endothelial cell (EC) barrier dysfunction. However, cellular mechanotransduction complexes remain to be characterized. This study tested a hypothesis that recovery of a vascular EC barrier after pathologic mechanical stress may be accelerated by cell exposure to physiologic CS levels and involves Rap1-dependent rearrangement of endothelial cell junctions. Using biochemical, molecular, and imaging approaches we found that EC pre- or postconditioning at physiologically relevant low-magnitude CS promotes resealing of cell junctions disrupted by pathologic, high-magnitude CS. Cytoskeletal remodeling induced by low CS was dependent on small GTPase Rap1. Protective effects of EC preconditioning at low CS were abolished by pharmacological or molecular inhibition of Rap1 activity. In vivo, using mice exposed to mechanical ventilation, we found that the protective effect of low tidal volume ventilation against lung injury caused by lipopolysaccharides and ventilation at high tidal volume was suppressed in Rap1 knockout mice. Taken together, our results demonstrate a prominent role of Rap1-mediated signaling mechanisms activated by low CS in acceleration of lung vascular EC barrier restoration.

scholarly journals Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xin-Yang Wang ◽  
Xin-Yu Li ◽  
Cheng-Hua Wu ◽  
Yu Hao ◽  
Pan-Han Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Tissue Regeneration ◽  
Umbilical Vein ◽  
Endothelial Glycocalyx ◽  
Lipid Mediator ◽  
Protective Effects ◽  
Pulmonary Vascular Permeability

Abstract Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

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