ABSTRACT: This project focuses both on the separate and combined effects of large tidal volume ventilation and hyperoxia on gene expression in the lungs of anesthetized rats. Rats were either mechanically or spontaneously ventilated at either 21 or 100% oxygen and expression levels were evaluated on RG_U34 GeneChips. Keywords: other
Project description:This project focuses both on the separate and combined effects of large tidal volume ventilation and hyperoxia on gene expression in the lungs of anesthetized rats. Rats were either mechanically or spontaneously ventilated at either 21 or 100% oxygen and expression levels were evaluated on RG_U34 GeneChips.
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.
Project description:This study was undertaken to examine differential gene expression across the whole genome during short-term ventilator-induced lung injury in mice, a commonly used model of acute lung injury, as compared with spontaneous ventilation. Experiment Overall Design: Mice were anesthetized with isoflurane followed by ketamine/xylaxine. Saline (0.25 ml) was given every hour ip. A tracheotomy tube was placed and the mice were ventilated with an initial peak airway pressure of 20 cmH2O approximating a tidal volume of 20 ml/kg and without end-expiratory pressure. Ventilation was continued for 3h. Tidal volume was not adjusted. Body temperature was monitored with a digital rectal thermometer and maintained at 37C with a heating table and external heating lamp. Control mice were treated identically, but were not mechanically ventilated (i.e. breathed spontaneously). There were 5 biological relicates in each group.
Project description:Introduction: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 mL/kg) tidal volume (VT) ventilation with open lung positive end-expiratory pressure set according to the minimal static elastance of the respiratory system (LVT/OLPEEP), attenuate the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 mL/kg) VT and low PEEP ventilation (HVT/LPEEP). Methods: Twenty-eight adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LVT/OLPEEP; 2) NBD with HVT/LPEEP; 3) brain damage (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analysed. Whole genome analysis was performed using Affimetrix gene chips and confirmatory real-time PCR. Results: In NBD, both LVT/OLPEEP and HVT/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time PCR. In BD, LVT/OLPEEP, compared to HVT/LPEEP, reduced lung damage according to histology, genome analysis and real-time PCR with decreased interleukin (IL-6), cytokine-induced neutrophil chemoattractant (CINC)-1 and angiopoietin-4 expressions. LVT/OLPEEP compared to HVT/LPEEP improved overall survival. Conclusions: In BD, LVT/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HVT/LPEEP. LVT/OLPEEP might represent a suitable ventilatory strategy in massive brain damage. 24 Wistar rats - lung samples, 4 groups, 1. non-braindamaged/braindead high tidal volume ventilation, 2. non-braindamaged/braindead best PEEP ventilation, 3. Braindamaged/braindead high tidal volume ventilation, 4. Braindamaged/braindead best PEEP ventilation
Project description:Gene expression profiling was performed in lung tissues from an animal model of sepsis challenged with injurious and non-injurious mechanical ventilation to unravel the molecular pathways involved in acute lung injury. Sepsis was induced in male Sprague Dawley rats by means of cecal ligation and puncture. Septic rats were randomly allocated to three distinct groups: spontaneous breathing, mechanically ventilated with high tidal volume with zero positive end expiratory pressure (PEEP) and with low tidal volume and 10 cmH2O of PEEP. Comparisons were performed against an unventilated control group.
Project description:Introduction: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 mL/kg) tidal volume (VT) ventilation with open lung positive end-expiratory pressure set according to the minimal static elastance of the respiratory system (LVT/OLPEEP), attenuate the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 mL/kg) VT and low PEEP ventilation (HVT/LPEEP). Methods: Twenty-eight adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LVT/OLPEEP; 2) NBD with HVT/LPEEP; 3) brain damage (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analysed. Whole genome analysis was performed using Affimetrix gene chips and confirmatory real-time PCR. Results: In NBD, both LVT/OLPEEP and HVT/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time PCR. In BD, LVT/OLPEEP, compared to HVT/LPEEP, reduced lung damage according to histology, genome analysis and real-time PCR with decreased interleukin (IL-6), cytokine-induced neutrophil chemoattractant (CINC)-1 and angiopoietin-4 expressions. LVT/OLPEEP compared to HVT/LPEEP improved overall survival. Conclusions: In BD, LVT/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HVT/LPEEP. LVT/OLPEEP might represent a suitable ventilatory strategy in massive brain damage.
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.
Project description:Acute respiratory distress syndrome (ARDS) results in significant morbidity and mortality, especially in the elderly. Mechanical ventilation, a common supportive treatment for ARDS, is necessary for maintaining gas exchange, but can also propagate injury. We hypothesized that aging would exacerbate the pathophysiological responses to mechanical ventilation. Young and aged male mice were mechanically ventilated and changes in surfactant function, inflammation, and vascular permeability were assessed. Additionally, single-cell RNA sequencing was used to delineate cell-specific transcriptional changes. The results showed that surfactant dysfunction was augmented in aged mice, while inflammation was less pronounced in aged animals. Futhermore, vascular permeability was significantly increased with aging. Differential gene expression and pathway analyses revealed that aged endothelial cells exhibited altered cell-cell junction formation and that alveolar macrophages in aged mice showed a blunted inflammatory response. These results highlight the complex interplay between aging and mechanical ventilation, including an age-related predisposition to endothelial barrier dysfunction due to altered cell-cell junction formation and decreased inflammation, potentially due to immune exhaustion. It is concluded that age-related vascular changes may underlie the increased susceptibility to injury during mechanical ventilation in elderly patients.
Project description:We sought to confirm the genetic influence in the development of Ventilation-Associated Lung Injury (VALI) and, in the process, identify potential candidate genes involved in the disease by integrating differential gene expression profiling on rat lungs to a traditional strain survey analysis of the parental rat strains, VALI-sensitive Brown Norway rats versus VALI-resistant Dahl Salt Sensitive rats, comparing control (under room air ventilation) versus under high tidal volume (HTV) ventilation. We used microarrays to detail the global programme of gene expression underlying VALI susceptibility and identified distinct classes of up-regulated and down-regulated genes during this process. Experiment Overall Design: Rat lungs (Right lungs) from both sets of parents under the two conditions (control vs. HTV ventilation) were isolated for RNA extraction and hybridization on Affymetrix microarrays.
Project description:To investigate the effect of mechanical ventilation and mechanical ventilationon with PEEP application on diaphragmatic dysfunction, we established a model of mechanical ventilation on New Zealand rabbit, in which rabbits in the experimental group were ventilated with/without PEEP application for 48 hours continuously