Age Dependent Gene Expression Responses to Inhaled Lipopolysaccharide Combined with Mechanical Ventilation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE18341 | GEO | 2009/11/23
SECONDARY ACCESSION(S): PRJNA118011
REPOSITORIES: GEO
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Project description:Children have a lower incidence and mortality from acute lung injury than adults, and infections are the most common event associated with acute lung injury (ALI). To study the effects of age on susceptibility to ALI, we investigated the responses to microbial products combined with mechanical ventilation in juvenile (21 day) and adult (16 week-old) mice. We hypothesized that the increased incidence and severity of lung injury associated with increasing age is due in large part to acquired changes in the way in which inflammatory responses are activated in the lungs in response to microbial products and mechanical ventilation. Juvenile (21 day) and adult (16 week) C57BL/6 mice were treated with an aerosol of E. coli 0111:B4 lipopolysaccharide (LPS) (20 mL of 0.1 mg/mL) for 30 minutes in a sealed aerosol chamber, immediately followed by mechanical ventilation (LPS+MV) using tidal volume = 15 mL/kg, rate = 80 breaths/min, FiO2 = 30% and positive end expiratory pressure = 2 cm H2O for the duration of the study period time = 2 hours. Comparison groups included mice treated with LPS or mechanical ventilation (MV) alone, and untreated age-matched controls. There were N = 4 animals per group except the juvenile mice treated with MV alone and LPS+MV where there were N = 3. Each sample was an individual animal, therefore there were 30 samples. Mice treated with LPS alone were placed into a sealed aerosol chamber as stated above, and then allowed to breath spontaneously with free access to food and water for the duration of the study period time = 2 hours. Mice treated with MV alone were treated with the mechanical ventilation protocol stated above for the duration of the study period time = 2 hours. At the end of the study period, the mice were euthanized, and the lungs were immediately removed and placed into RNAlater (Ambion, Austin, TX) for at least 24 hr prior to isolation of total lung mRNA.
2009-11-23 | E-GEOD-18341 | biostudies-arrayexpress
Project description:Postoperative Pulmonary Complications (PPC) are very common. It severely affects postoperative recovery, particularly in the abdominal surgery. Patients with laparoscopic resection of colorectal cancer generally have a higher age and decreased lung function reserve. At the same time, they prone to developing atelectasis due to the effects of pneumoperitoneum pressure. Therefore, they are a high-risk group of respiratory insufficiency and PPC.
Mechanical ventilation with a low tidal volume is a routine in clinic nowadays. However, this conventional strategy will also result in atelectasis formation. Therefore, it may deteriorate the vulnerable lung function of patients undergoing laparoscopic resection of colorectal cancer. Patients with Acute Lung Injury or Acute Respiratory Distress Syndrome (ALI/ARDS) could benefit from the "open lung approach", including the use of positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs). Whether a lung protective mechanical ventilation strategy with medium levels of PEEP and repeated RMs, the "open lung approach", protects against respiratory insufficiency and PPC during laparoscopic resection of colorectal cancer is uncertain. The present study aims at comparing the effects of "open lung approach" mechanical ventilation strategy and conventional mechanical ventilation strategy in PPC, extra-pulmonary complications, length of hospital stay, biomarkers of lung injury and changes of respiratory function in patients undergoing general anesthesia for laparoscopic resection of colorectal cancer.
| 2244915 | ecrin-mdr-crc
Project description:To study the effects of previous exposure to mechanical ventilation may modify the development of Ventilator-induced lung injury, preconditioning was induced by low-pressure ventilation for 90 minutes. After 1 week, intact (sham) and preconditioned mice were sacrificed, the lungs extracted and gene expression measured in order to identify differences responsible for the observed tolerance to ventilator-induced lung injury observed in preconditioned animals. 6 samples were analyzed, from 3 intact (sham) and 3 preconditioned CD1 mice.
2015-08-21 | E-GEOD-65783 | biostudies-arrayexpress
Project description:To study the effects of previous exposure to mechanical ventilation may modify the development of Ventilator-induced lung injury, preconditioning was induced by low-pressure ventilation for 90 minutes. After 1 week, intact (sham) and preconditioned mice were sacrificed, the lungs extracted and gene expression measured in order to identify differences responsible for the observed tolerance to ventilator-induced lung injury observed in preconditioned animals.
2015-08-21 | GSE65783 | GEO
Project description:Scientific knowledge on the subjects: Injurious mechanical ventilation amplifies acute lung injury in a heterogeneous and regional fashion but the molecular mechanisms underlying regional lung injury and the protective effects of prone positioning are unclear. Regionally injurious ventilation is associated with discrete differential lung transcriptomic changes. Ventilating in the prone, compared with the supine position abrogates regional injury by depressing MKP-1.
2011-08-27 | GSE31678 | GEO
Project description:Scientific knowledge on the subjects: Injurious mechanical ventilation amplifies acute lung injury in a heterogeneous and regional fashion but the molecular mechanisms underlying regional lung injury and the protective effects of prone positioning are unclear. Regionally injurious ventilation is associated with discrete differential lung transcriptomic changes. Ventilating in the prone, compared with the supine position abrogates regional injury by depressing MKP-1. Adult rats were ventilated with high (18 mL/Kg, PEEP 0) tidal volume (Vt) in supine or prone position. Non ventilated rats were used as controls. Dorsal-caudal lung mRNA was analyzed by microarray.
2011-08-26 | E-GEOD-31678 | biostudies-arrayexpress
Project description:In 1967, the term "respirator lung" was coined to describe the diffuse alveolar infiltrates and hyaline membranes that were found on postmortem examination of patients who had undergone mechanical ventilation.This mechanical ventilation can aggravate damaged lungs and damage normal lungs. In recent years, Various ventilation strategies have been used to minimize lung injury, including low tide volume, higher PEEPs, recruitment maneuvers and high-frequency oscillatory ventilation. which have been proved to reduce the occurrence of lung injury.
In 2012,Needham et al. proposed a kind of lung protective mechanical ventilation, and their study showed that limited volume and pressure ventilation could significantly improve the 2-year survival rate of patients with acute lung injury.Volume controlled ventilation is the most commonly used method in clinical surgery at present.Volume controlled ventilation(VCV) is a time-cycled, volume targeted ventilation mode, ensures adequate gas exchange. Nevertheless, during VCV, airway pressure is not controlled.Pressure controlled ventilation（PCV） can ensure airway pressure,however minute ventilation is not guaranteed.Pressure controlled ventilation-volume guarantee(PCV-VG) is an innovative mode of ventilation utilizes a decelerating flow and constant pressure. Ventilator parameters are automatically changed with each patient breath to offer the target VT without increasing airway pressures. So PCV-VG has the advantages of both VCV and PCV to preserve the target minute ventilation whilst producing a low incidence of barotrauma pressure-targeted ventilation.
Current studies on PCV-VG mainly focus on thoracic surgery, bariatric surgery and urological surgery, and the research indicators mainly focus on changes in airway pressure and intraoperative oxygenation index.The age of patients undergoing laparoscopic colorectal cancer resection is generally higher, the cardiopulmonary reserve function is decreased, and the influence of intraoperative pneumoperitoneum pressure and low head position increases the incidence of intraoperative and postoperative pulmonary complications.Whether PCV-VG can reduce the incidence of intraoperative lung injury and postoperative pulmonary complications in elderly patients undergoing laparoscopic colorectal cancer resection, and thereby improve postoperative recovery of these patients is still unclear.
| 2306393 | ecrin-mdr-crc
Project description:In the present study we seek to identify changes in lung gene expression under mechanical ventilation in uninjured as well as acutely and chronically injured lungs. A standard volume-controlled lung-protective ventilatory protocol is compared to a concept of mechanical ventilation using variable tidal volumes.
2017-02-17 | GSE78008 | GEO
Project description:We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI. Experiment Overall Design: animals were treated by PBS, rhPBEF (IT administration), VILI (4 hours, 30 ml/kg tidal volume), or both.
2008-06-16 | E-GEOD-9314 | biostudies-arrayexpress
Project description:We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Experiment Overall Design: animals were treated by PBS, rhPBEF (IT administration), VILI (4 hours, 30 ml/kg tidal volume), or both.
2008-06-16 | E-GEOD-9368 | biostudies-arrayexpress