Comparison of direct and indirect models of early induced acute lung injury.

Background: The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS.

Aim: To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS.

Alveolar Type II Cells or Mesenchymal Stem Cells: Comparison of Two Different Cell Therapies for the Treatment of Acute Lung Injury in Rats.

The use of cell therapies has recently increased for the treatment of pulmonary diseases. Mesenchymal stem/stromal cells (MSCs) and alveolar type II cells (ATII) are the main cell-based therapies used for the treatment of acute respiratory distress syndrome (ARDS). Many pre-clinical studies have shown that both therapies generate positive outcomes; however, the differences in the efficiency of MSCs or ATII for reducing lung damage remains to be studied.

Effects of nebulized antithrombin and heparin on inflammatory and coagulation alterations in an acute lung injury model in rats.

Background: During acute respiratory distress syndrome, proinflammatory mediators inhibit natural anticoagulant factors, which alter the normal balance between coagulation and fibrinolysis leading to a procoagulant state. We hypothesize that pulmonary administration of anticoagulants might be beneficial to treat acute respiratory distress syndrome for their anticoagulant and antiinflammatory effects and reduce the risk of systemic bleeding.

Objectives: Our aim is to study the effects of nebulized antithrombin (AT) and combined AT and heparin in an animal model of acute lung injury.

Fas activation alters tight junction proteins in acute lung injury.

The acute respiratory distress syndrome (ARDS) is characterized by protein-rich oedema in the alveolar spaces, a feature in which Fas-mediated apoptosis of the alveolar epithelium has been involved. To determine whether Fas activation increases protein permeability by mechanisms involving disruption of the paracellular tight junction (TJ) proteins in the pulmonary alveoli. Protein permeability and the expression of TJ proteins were assessed in vivo in wild-type and Fas-deficient lpr mice 16 hours after the intratracheal instillation of recombinant human soluble Fas ligand (rh-sFasL), and at different time points in vitro in human pulmonary alveolar epithelial cells (HPAEpiC) exposed to rh-sFasL Activation of the Fas pathway increased protein permeability in mouse lungs and altered the expression of the TJ proteins occludin and zonula occludens-1 in the alveolar-capillary membrane in vivo and in human alveolar epithelial cell monolayers in vitro.

Barrier-protective effects of activated protein C in human alveolar epithelial cells.

Acute lung injury (ALI) is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI.

Early physiological and biological features in three animal models of induced acute lung injury.

Introduction: Critically ill patients often develop acute lung injury (ALI) in the context of different clinical conditions. We aimed to explore differences in early local and systemic features in three experimental animal models of ALI.

Methods: Mechanically ventilated male Sprague-Dawley rats were randomized to high tidal volume (VT) ventilation (HVT) (n = 8, VT 24 ml/kg), massive brain injury (MBI) (n = 8, VT 8 ml/kg) or endotoxemia (LPS) (n = 8, VT 8 ml/kg).

Upper-airway inflammation triggered by vibration in a rat model of snoring.

Study Objectives: To determine whether the vibratory mechanical stimulus due to snoring induces upper-airway inflammation in an in-vivo rat model.

Design: Prospective controlled animal study.

Setting: University laboratory.

Effect of stretch on structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin.

Alveolar epithelial cells in patients with acute lung injury subjected to mechanical ventilation are exposed to increased procoagulant activity and mechanical strain. Thrombin induces epithelial cell stiffening, contraction, and cytoskeletal remodeling, potentially compromising the balance of forces at the alveolar epithelium during cell stretching. This balance can be further compromised by the loss of integrity of cell-cell junctions in the injured epithelium.

Vibration enhances interleukin-8 release in a cell model of snoring-induced airway inflammation.

Study Objectives: To test a cell model of snoring-induced airway inflammation and to assess whether a vibration stimulus simulating the one experienced by airway tissues in snoring patients induces inflammation in airway epithelial cells.

Design: Prospective controlled study in cell culture.

Setting: University laboratory.

Viscoelasticity of human alveolar epithelial cells subjected to stretch.

Alveolar epithelial cells undergo stretching during breathing and mechanical ventilation. Stretch can modify cell viscoelastic properties, which may compromise the balance of forces in the alveolar epithelium. We studied the viscoelasticity of alveolar epithelial cells (A549) subjected to equibiaxial distention with a novel experimental approach.