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Supplemental Digital Content 1Detailed MethodsStudy approvalThis study was approved by the Animal Care and Use Committee (CEUA: 086/17) of the Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the U.S. National Academy of Sciences Guide for the Care and Use of Laboratory Animals. The present study followed the ARRIVE guidelines for reporting of animal research.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaWxrZW5ueTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
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ADDIN EN.CITE.DATA 1 Animal preparation and experimental protocolSixty-four male Wistar rats (8-10 weeks, weight 376 ± 52 g) were anesthetized by inhalation of 2% sevoflurane (Sevorane?; Cristália, Itapira, SP, Brazil), and received intratracheal (i.t.) instillation of Escherichia coli lipopolysaccharide (O55:B5, LPS Ultrapure, Invivogen), 200 ?g suspended in saline solution to a total volume of 200 ?LPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYW1hcnk8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 2, to induce acute respiratory distress syndrome (ARDS). After 24 h, during the morning, animals were premedicated intraperitoneally (i.p.) with 10 mg/kg diazepam (Compaz, Cristália, Itapira, SP, Brazil), followed by 100 mg/kg ketamine (Ketamin-S+, Cristália, Itapira, SP, Brazil) and 2 mg/kg midazolam (Dormicum, Uni?o Química, S?o Paulo, SP, Brazil). After local anesthesia with 2% lidocaine (0.4?mL), a midline neck incision and tracheostomy were performed. Eight rats were used for molecular biology analysis and were not mechanically ventilated (non-ventilated, NV).An intravenous (i.v.) catheter (Jelco 24G, Becton, Dickinson and Company, New Jersey, NJ, USA) was inserted into the tail vein, and anesthesia induced and maintained with midazolam (2?mg/kg/h) and ketamine (50?mg/kg/h). Additionally, 10 mL/kg/h Ringer’s lactate (B. Braun, Crissier, Switzerland) was administered i.v. Gelafundin? 4% (B. Braun, S?o Gon?alo, RJ, Brazil) was administered intravenously (in 0.5-mL increments) to maintain mean arterial pressure (MAP) ≥ 70 mmHg. A second catheter (18G, Arrow International, USA) was then placed in the right internal carotid artery for blood sampling and gas analysis (Radiometer ABL80 FLEX, Copenhagen NV, Denmark), as well as monitoring of MAP (Networked Multiparameter Veterinary Monitor LifeWindow 6000?V; Digicare Animal Health, Boynton Beach, FL, USA). A 30-cm-long water-filled catheter (PE-205, Becton, Dickinson and Company) with side holes at the tip, connected to a differential pressure transducer (UT-PL-400, SCIREQ, Montreal, QC, Canada), was used to measure the esophageal pressure (Pes). Proper positioning was assessed with the “occlusion test”. ADDIN EN.CITE <EndNote><Cite><Author>Baydur</Author><Year>1982</Year><RecNum>9619</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>9619</rec-number><foreign-keys><key app="EN" db-id="2xvvrsvxi59a2yetwwsx0ddlz0r9wrxsppvf">9619</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Baydur, A.</author><author>Behrakis, P. K.</author><author>Zin, W. A.</author><author>Jaeger, M.</author><author>Milic-Emili, J.</author></authors></contributors><titles><title>A simple method for assessing the validity of the esophageal balloon technique</title><secondary-title>The American review of respiratory disease</secondary-title><alt-title>Am Rev Respir Dis</alt-title></titles><periodical><full-title>The American review of respiratory disease</full-title><abbr-1>Am Rev Respir Dis</abbr-1></periodical><alt-periodical><full-title>The American review of respiratory disease</full-title><abbr-1>Am Rev Respir Dis</abbr-1></alt-periodical><pages>788-91</pages><volume>126</volume><number>5</number><edition>1982/11/01</edition><keywords><keyword>Adult</keyword><keyword>Esophagus/*physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Manometry/*methods</keyword><keyword>Pleura/*physiology</keyword><keyword>Posture</keyword><keyword>Pressure</keyword></keywords><dates><year>1982</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0003-0805 (Print)
0003-0805 (Linking)</isbn><accession-num>7149443</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls><related-urls><url> Heart rate (HR), MAP, and rectal temperature were continuously monitored (Networked Multiparameter Veterinary Monitor LifeWindow 6000V, Digicare Animal Health, Florida, USA). Body temperature was maintained at 37.5±1 °C using a heating bed. Animals were paralyzed with pancuronium bromide (2 mg/kg, i.v.), and their lungs mechanically ventilated (V500; Dr?ger Medical, Lübeck, Germany) in volume-controlled mode (VCV) with constant inspiratory airflow, tidal volume (VT)=6 mL/kg, positive end-expiratory pressure (PEEP)=3 cmH2O, RR adjusted to PaCO2=35–45 mmHg (around 70 bpm), FiO2=0.4, and an inspiratory-expiratory ratio of 1:2 (figure 1). Arterial blood gases (300 ?l) were determined using a Radiometer ABL80 FLEX analyzer (Copenhagen NV, Denmark) and respiratory system mechanics were assessed (INITIAL). Animals were then randomly assigned to receive (n=8/group): mechanical ventilation with a protective strategy (VT=6mL/kg) for 2 hours (Control); VT=6mL/kg during hour 1 followed by an abrupt increase of VT=22mL/kg until 2 hours (No adaptation time); VT=6mL/kg during the first 30 minutes followed by a gradual VT increase up to 22mL/kg for 30 minutes, then constant VT=22mL/kg until 2 hours (Shorter adaptation time); and a more gradual VT increase, from 6mL/kg to 22mL/kg during 1 hour followed by VT=22mL/kg until 2 hours (Longer adaptation time). The VT size of 22 mL/kg was chosen because it has been shown to promote VILI yet allow survival for 2 h. ADDIN EN.CITE <EndNote><Cite><Author>Samary</Author><Year>2016</Year><RecNum>9625</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>9625</rec-number><foreign-keys><key app="EN" db-id="2xvvrsvxi59a2yetwwsx0ddlz0r9wrxsppvf">9625</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Samary, C. S.</author><author>Silva, P. L.</author><author>Gama de Abreu, M.</author><author>Pelosi, P.</author><author>Rocco, P. R.</author></authors></contributors><auth-address>Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (P.R.M.R.). prmrocco@.</auth-address><titles><title>Ventilator-induced Lung Injury: Power to the Mechanical Power</title><secondary-title>Anesthesiology</secondary-title><alt-title>Anesthesiology</alt-title></titles><periodical><full-title>Anesthesiology</full-title><abbr-1>Anesthesiology</abbr-1></periodical><alt-periodical><full-title>Anesthesiology</full-title><abbr-1>Anesthesiology</abbr-1></alt-periodical><pages>1070-1071</pages><volume>125</volume><number>5</number><edition>2016/10/19</edition><dates><year>2016</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1528-1175 (Electronic)
0003-3022 (Linking)</isbn><accession-num>27755035</accession-num><urls><related-urls><url> Respiratory system mechanics were measured every 30 min and at the end of the experiment (FINAL). At FINAL, arterial blood gases were also analyzed, heparin (1000 IU) was injected into the tail vein. The trachea was then clamped at the same airway pressure used at end-expiration (PEEP = 3 cmH2O) and all animals were killed by an overdose of sodium thiopental (60 mg/kg i.v.) followed by transection of the abdominal aorta and vena cava. Lungs were then extracted for histology and molecular biology analyses. In order to dissociate the effects of the gradual increase of VT from the association between gradual VT increase and VTH maintenance, we also evaluated 1 h mechanical ventilation effects. For this purpose, 24 animals were ventilated in groups A, C, and D (n=8/group) and euthanized at 1 hour. Heterogeneity index, DAD score, and gene expression of biomarkers were then measured. EchocardiographyShaved animals were placed in the dorsal recumbent position. Transthoracic echocardiography was performed by an expert (N.N.R.) blinded to group allocation, using an UGEO HM70A system (Samsung, S?o Paulo, Brazil) equipped with a linear phased-array probe (8–13 MHz). Measurements were obtained in accordance with American Society of Echocardiography guidelines PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYW5nPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 5. Images were obtained from the subcostal and parasternal views. The left ventricular ejection fraction (EF%) and cardiac output (L/min) were calculated in one-dimensional mode analysis of the left ventricle guided by the parasternal short-axis view. Pulsed-wave Doppler was used to measure the ratio between pulmonary acceleration time (PAT) and pulmonary ejection time (PET), which is an indirect?index of pulmonary arterial hypertension. Heart rate was assessed from the subcostal view. Data Acquisition and ProcessingA pneumotachograph (internal diameter = 1.5 mm, length = 4.2 cm, distance between side ports = 2.1 cm) was connected to the tracheal cannula for airflow (V?) measurements. ADDIN EN.CITE <EndNote><Cite><Author>Mortola</Author><Year>1983</Year><RecNum>9644</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>9644</rec-number><foreign-keys><key app="EN" db-id="2xvvrsvxi59a2yetwwsx0ddlz0r9wrxsppvf">9644</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mortola, J. P.</author><author>Noworaj, A.</author></authors></contributors><titles><title>Two-sidearm tracheal cannula for respiratory airflow measurements in small animals</title><secondary-title>Journal of applied physiology: respiratory, environmental and exercise physiology</secondary-title><alt-title>J Appl Physiol Respir Environ Exerc Physiol</alt-title></titles><periodical><full-title>Journal of applied physiology: respiratory, environmental and exercise physiology</full-title><abbr-1>J Appl Physiol Respir Environ Exerc Physiol</abbr-1></periodical><alt-periodical><full-title>Journal of applied physiology: respiratory, environmental and exercise physiology</full-title><abbr-1>J Appl Physiol Respir Environ Exerc Physiol</abbr-1></alt-periodical><pages>250-3</pages><volume>55</volume><number>1 Pt 1</number><edition>1983/07/01</edition><keywords><keyword>Animals</keyword><keyword>Catheterization/*instrumentation</keyword><keyword>*Pulmonary Ventilation</keyword><keyword>Tidal Volume</keyword><keyword>*Trachea</keyword></keywords><dates><year>1983</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0161-7567 (Print)
0161-7567 (Linking)</isbn><accession-num>6885578</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls><related-urls><url> The pressure gradient across the pneumotachograph was determined using a SCIREQ differential pressure transducer (UT-PDP-02, SCIREQ, Montreal, QC, Canada). Airflow, airway pressure (Paw), and Pes were continuously recorded throughout the experiments with a computer running custom-made software written in LabVIEW (National Instruments, Austin, TX).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYW1hcnk8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 7,8 Briefly, VT was calculated by digital integration of the airflow signal obtained from a custom-made pneumotachograph ADDIN EN.CITE <EndNote><Cite><Author>Mortola</Author><Year>1983</Year><RecNum>9644</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>9644</rec-number><foreign-keys><key app="EN" db-id="2xvvrsvxi59a2yetwwsx0ddlz0r9wrxsppvf">9644</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mortola, J. P.</author><author>Noworaj, A.</author></authors></contributors><titles><title>Two-sidearm tracheal cannula for respiratory airflow measurements in small animals</title><secondary-title>Journal of applied physiology: respiratory, environmental and exercise physiology</secondary-title><alt-title>J Appl Physiol Respir Environ Exerc Physiol</alt-title></titles><periodical><full-title>Journal of applied physiology: respiratory, environmental and exercise physiology</full-title><abbr-1>J Appl Physiol Respir Environ Exerc Physiol</abbr-1></periodical><alt-periodical><full-title>Journal of applied physiology: respiratory, environmental and exercise physiology</full-title><abbr-1>J Appl Physiol Respir Environ Exerc Physiol</abbr-1></alt-periodical><pages>250-3</pages><volume>55</volume><number>1 Pt 1</number><edition>1983/07/01</edition><keywords><keyword>Animals</keyword><keyword>Catheterization/*instrumentation</keyword><keyword>*Pulmonary Ventilation</keyword><keyword>Tidal Volume</keyword><keyword>*Trachea</keyword></keywords><dates><year>1983</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0161-7567 (Print)
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ADDIN EN.CITE.DATA 7 Respiratory system driving pressure (?P,RS) was calculated as the difference between Pplat,RS (post end-inspiratory pause) and PEEP. Transpulmonary pressure (P,L) was calculated as the difference between the Paw and Pes, whereas transpulmonary driving pressure (ΔP,L) was the difference between the transpulmonary pressure at end-inspiration (post-inspiratory pause) and end-expiration. Measurement of Mechanical Power, Energy, and Driving PressureThe mechanical power applied by the ventilator to the respiratory system was calculated as the product of energy and RR. The mechanical energy, in turn, was calculated using the following equation: Energy,L?= ΔP,2L/Est,L, where Est,L?is the static lung elastance; Energy,L?= ΔP,2L/(ΔP,L/VT) = ΔP,LxVT, which is the area of a rectangle.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYW50b3M8L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 9,10 Therefore, one must compute the area of the rectangle and divide the result by 2. Values were converted to mJ and multiplied by RR to obtain the mechanical power in mJ/min. This equation estimates the elastic work (the major component of total work) without taking into account resistive properties or PEEP.Cumulative power was calculated for 1 and 2 hours. All signals were amplified in a four-channel signal conditioner (SC-24, SCIREQ, Montreal, QC, Canada), and sampled at 200 Hz with a 12-bit analogue-to-digital converter (National Instruments; Austin, Texas, USA). Mechanical data were computed offline by a routine written in MATLAB (Version R2007a; The Mathworks Inc., Natick, Massachusetts, USA).HistologyThe lungs and heart were removed en bloc. The left lung was frozen in liquid nitrogen and immersed in formaldehyde solution (4%), embedded in paraffin, cut longitudinally in the central zone by means of a microtome into three slices, each 4 μm thick, and stained with hematoxylin–eosin for histological analysis.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYW1hcnk8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 7,11 Photomicrographs at magnifications of ×100, ×200, and ×400 were obtained from eight non-overlapping fields of view per section using a light microscope (Olympus BX51, Olympus Latin America Inc., Brazil). Diffuse alveolar damage (DAD) was quantified using a weighted scoring system by two investigators (V.M. and V.L.C.) blinded to group assignment and independently, as described elsewhere.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaXNzPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 12 Briefly, scores of 0 to 4 were used to represent atelectasis, ductal overdistension, interstitial edema, inflammation, and detachment of airway epithelium, with 0 standing for no effect and 4 for maximum severity. Additionally, the extent of each scored characteristic per field of view was determined on a scale of 0 to 4, with 0 standing for no visible evidence and 4 for complete involvement. Scores were calculated as the product of severity and extent of each feature, on a range of 0 to 16. The cumulative DAD score was calculated as the sum of each score characteristic and ranged from 0 to 80. Airspace enlargement was assessed by measuring the mean linear intercept (Lm) between alveolar walls at a magnification of ×400.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ic2lhPC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 13 To characterize the heterogeneity of airspace enlargement, the mean linear intercept (D2?of Lm) was computed from 20 airspace measurements PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWVyemNob248L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFy
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ADDIN EN.CITE.DATA 15Biological Markers Quantitative real-time reverse transcription polymerase chain reaction (PCR) was performed by an investigator (F.C.) blinded to group assignment, to measure biomarkers associated with inflammation (interleukin [IL]-6), mechanical pulmonary stretch (amphiregulin) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Eb2xpbmF5PC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48
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ADDIN EN.CITE.DATA 20 and expressed as fold change relative to respective NV animals, using the 2–??Ct method, where ΔCt = Ct (target gene)?– Ct (reference gene).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TY2htaXR0Z2VuPC9BdXRob3I+PFllYXI+MjAwODwvWWVh
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ADDIN EN.CITE.DATA 21Statistical analysisThe sample size was calculated to allow detection of the differences in IL-6 among ventilatory strategies, which was expected between VT = 6 and 22 mL/kg, based on previous work from our group.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYW1hcnk8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 7 A sample size of 8 animals per group would provide the appropriate power (1 ? β = 0.8) to identify statistically significant differences in IL-6 (adjusted α = 0.025 for two comparisons), taking into account an effect size d = 2.0, a two-sided t-test, and a sample size ratio = 1 (G*Power 3.1.9.2, University of Düsseldorf, Düsseldorf, Germany). The primary outcome was the difference in gene expression of IL-6 among ventilatory strategies, whereas the secondary outcomes were lung function, heterogeneity index, diffuse alveolar damage score, and expression of genes related to alveolar stretch, epithelial and endothelial cell injuries, and extracellular matrix damage.Data were tested for normality using the Kolmogorov-Smirnov test with Lilliefors’ correction, while the Levene median test was used to evaluate the homogeneity of variances. If both conditions were satisfied, time-dependent differences among groups were determined with mixed linear models based on a random intercept for each animal followed by Bonferroni tests. Molecular biology variables and DAD score were assessed with the Kruskal-Wallis test followed by Dunn’s test. Spearman correlation was performed. Parametric data were expressed as mean ± SD, while nonparametric data were expressed as median (interquartile range). Mixed linear models and multiple linear regression analyses were carried out in IBM SPSS Statistics for Windows, Version 19.0 (IBM Corp., USA). All the other tests were carried out in GraphPad Prism 6.00 (GraphPad Software, La Jolla, CA, USA). No outliers were excluded from the analysis. Significance was established at p<0.05.References ADDIN EN.REFLIST 1.Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG: Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 2010; 8: e10004122.Samary CS, Moraes L, Santos CL, Huhle R, Santos RS, Ornellas DS, Felix NS, Capelozzi VL, Schanaider A, Pelosi P, de Abreu MG, Rocco PR, Silva PL: Lung Functional and Biologic Responses to Variable Ventilation in Experimental Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome. Crit Care Med 2016; 44: e553-5623.Baydur A, Behrakis PK, Zin WA, Jaeger M, Milic-Emili J: A simple method for assessing the validity of the esophageal balloon technique. Am Rev Respir Dis 1982; 126: 788-7914.Samary CS, Silva PL, Gama de Abreu M, Pelosi P, Rocco PR: Ventilator-induced Lung Injury: Power to the Mechanical Power. Anesthesiology 2016; 125: 1070-10715.Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU: Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 2015; 28: 1-39 e146.Mortola JP, Noworaj A: Two-sidearm tracheal cannula for respiratory airflow measurements in small animals. J Appl Physiol 1983; 55: 250-2537.Samary CS, Santos RS, Santos CL, Felix NS, Bentes M, Barboza T, Capelozzi VL, Morales MM, Garcia CS, Souza SA, Marini JJ, Gama de Abreu M, Silva PL, Pelosi P, Rocco PR: Biological Impact of Transpulmonary Driving Pressure in Experimental Acute Respiratory Distress Syndrome. Anesthesiology 2015; 123: 423-338.Spieth PM, Silva PL, Garcia CS, Ornellas DS, Samary CS, Moraes L, Bentes M, Morales MM, Kasper M, Guldner A, Huhle R, Koch T, Pelosi P, de Abreu MG, Rocco PR: Modulation of stress versus time product during mechanical ventilation influences inflammation as well as alveolar epithelial and endothelial response in rats. Anesthesiology 2015; 122: 106-1169.Santos RS, Maia LA, Oliveira MV, Santos CL, Moraes L, Pinto EF, Samary CDS, Machado JA, Carvalho AC, Fernandes MVS, Martins V, Capelozzi VL, Morales MM, Koch T, Gama de Abreu M, Pelosi P, Silva PL, Rocco PRM: Biologic Impact of Mechanical Power at High and Low Tidal Volumes in Experimental Mild Acute Respiratory Distress Syndrome. Anesthesiology 2018; 128: 1193-120610.Moraes L, Silva PL, Thompson A, Santos CL, Santos RS, Fernandes MVS, Morales MM, Martins V, Capelozzi VL, de Abreu MG, Pelosi P, Rocco PRM: Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats. Front Physiol 2018; 9: 31811.Padilha GA, Horta LF, Moraes L, Braga CL, Oliveira MV, Santos CL, Ramos IP, Morales MM, Capelozzi VL, Goldenberg RC, de Abreu MG, Pelosi P, Silva PL, Rocco PR: Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema. Intensive Care Med Exp 2016; 4: 3512.Kiss T, Silva PL, Huhle R, Moraes L, Santos RS, Felix NS, Santos CL, Morales MM, Capelozzi VL, Kasper M, Pelosi P, Gama de Abreu M, Rocco PR: Comparison of different degrees of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation. Br J Anaesth 2016; 116: 708-71513.Hsia CC, Hyde DM, Ochs M, Weibel ER: An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med 2010; 181: 394-41814.Wierzchon C, Padilha G, Rocha NN, Huhle R, Coelho MS, Santos CL, Santos RS, Samary CS, Silvino FRG, Pelosi P, Gama de Abreu M, Rocco PRM, Silva PL: Variability in Tidal Volume Affects Lung and Cardiovascular Function Differentially in a Rat Model of Experimental Emphysema. Front Physiol 2017; 8: 107115.Parameswaran H, Majumdar A, Ito S, Alencar AM, Suki B: Quantitative characterization of airspace enlargement in emphysema. J Appl Physiol 2006; 100: 186-9316.Dolinay T, Kaminski N, Felgendreher M, Kim HP, Reynolds P, Watkins SC, Karp D, Uhlig S, Choi AM: Gene expression profiling of target genes in ventilator-induced lung injury. Physiol Genomics 2006; 26: 68-7517.Brauer R, Ge L, Schlesinger SY, Birkland TP, Huang Y, Parimon T, Lee V, McKinney BL, McGuire JK, Parks WC, Chen P: Syndecan-1 Attenuates Lung Injury during Influenza Infection by Potentiating c-Met Signaling to Suppress Epithelial Apoptosis. Am J Respir Crit Care Med 2016; 194: 333-4418.Gonzalez-Lopez A, Astudillo A, Garcia-Prieto E, Fernandez-Garcia MS, Lopez-Vazquez A, Batalla-Solis E, Taboada F, Fueyo A, Albaiceta GM: Inflammation and matrix remodeling during repair of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2011; 301: L500-919.Patel S, Santra M, McQuillan DJ, Iozzo RV, Thomas AP: Decorin activates the epidermal growth factor receptor and elevates cytosolic Ca2+ in A431 carcinoma cells. J Biol Chem 1998; 273: 3121-312420.Akamine R, Yamamoto T, Watanabe M, Yamazaki N, Kataoka M, Ishikawa M, Ooie T, Baba Y, Shinohara Y: Usefulness of the 5' region of the cDNA encoding acidic ribosomal phosphoprotein P0 conserved among rats, mice, and humans as a standard probe for gene expression analysis in different tissues and animal species. J Biochem Biophys Methods 2007; 70: 481-48621.Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008; 3: 1101-1108 ................
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