Calcium restores the macrophage response to nontypeable haemophilus influenzae in chronic obstructive pulmonary disease.

Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have demonstrated impaired bacterial phagocytosis and disordered cytokine secretion, which are calcium-dependent processes. We determined how calcium moderates the macrophage response to nontypeable Haemophilus influenzae (NTHI). We hypothesized that augmenting extracellular calcium during bacterial challenge would restore bacterial phagocytosis and cytokine secretion in monocyte-derived macrophages (MDMs) from subjects with COPD.

Jamming dynamics of stretch-induced surfactant release by alveolar type II cells.

Secretion of pulmonary surfactant by alveolar epithelial type II cells is vital for the reduction of interfacial surface tension, thus preventing lung collapse. To study secretion dynamics, rat alveolar epithelial type II cells were cultured on elastic membranes and cyclically stretched. The amounts of phosphatidylcholine, the primary lipid component of surfactant, inside and outside the cells, were measured using radiolabeled choline.

Mechanical compression attenuates normal human bronchial epithelial wound healing.

Background: Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer.

Methods: Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1) unperturbed control cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH2O), and 4) 6 hours of static compression after a scrape wound.

Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture.

Secretion of pulmonary surfactant that maintains low surface tension within the lung is primarily mediated by mechanical stretching of alveolar epithelial type II (AEII) cells. We have shown that guinea pigs ventilated with random variations in frequency and tidal volume had significantly larger pools of surfactant in the lung than animals ventilated in a monotonous manner. Here, we test the hypothesis that variable stretch patterns imparted on the AEII cells results in enhanced surfactant secretion.

Design of a new stretching apparatus and the effects of cyclic strain and substratum on mouse lung epithelial-12 cells.

The pulmonary epithelium is exposed to mechanical strains during normal breathing or mechanical ventilation. While important for the regulation of cellular processes, excessive strains damage epithelial cells. To investigate the effects of strain on the epithelium, we developed a stretching device to apply equi-biaxial strains to cells cultured on elastic membranes.

Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model.

Objective: There has recently been considerable interest in alternative lung-protective ventilation strategies such as variable ventilation (VV). We aimed at testing VV in a large animal lung injury model and exploring the mechanism of improvement in gas exchange seen with VV.

Design: Randomized, controlled comparative ventilation study.

Tissue heterogeneity in the mouse lung: effects of elastase treatment.

We developed a network model in an attempt to characterize heterogeneity of tissue elasticity of the lung. The model includes a parallel set of pathways, each consisting of an airway resistance, an airway inertance, and a tissue element connected in series. The airway resistance, airway inertance, and the hysteresivity of the tissue elements were the same in each pathway, whereas the tissue elastance (H) followed a hyperbolic distribution between a minimum and maximum.

Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment.

We investigated the relationship between the microscopic elastic and hysteretic behavior of the alveolar walls and the macroscopic mechanical properties of the whole lung in an in vivo elastase-treated rat model of emphysema. We measured the input impedance of isolated lungs at three levels of transpulmonary pressure (Ptp) and used a linear model to estimate the dynamic elastance and hysteresivity of the lungs. The elastance of the normal lungs increased steeply with Ptp, whereas this dependence diminished in the treated lungs.

Variable ventilation induces endogenous surfactant release in normal guinea pigs.

Variable or noisy ventilation, which includes random breath-to-breath variations in tidal volume (Vt) and frequency, has been shown to consistently improve blood oxygenation during mechanical ventilation in various models of acute lung injury. To further understand the effects of variable ventilation on lung physiology and biology, we mechanically ventilated 11 normal guinea pigs for 3 h using constant-Vt ventilation (n = 6) or variable ventilation (n = 5). After 3 h of ventilation, each animal underwent whole lung lavage for determination of alveolar surfactant content and composition, while protein content was assayed as a possible marker of injury.

Physiology: Dynamic instabilities in the inflating lung.

In lung diseases such as asthma, expiratory flow becomes limited, airways can collapse and the vital exchange of gases is compromised. Here we model the inflation of collapsed regions of the lung during inspiration in terms of avalanches propagating through a bifurcating network of airways, and find that the accompanying cascade of dynamic pressure instabilities -- avalanche 'shocks' -- manifests as negative elastic resistance of the lung. Our analysis of this apparent thermodynamic paradox provides a better understanding of aeration in the deep regions of the lung, which may find application in medical conditions in which gas exchange is impaired.

Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury.

Random variations in breath rate and tidal volume during mechanical ventilation in the setting of acute lung injury have been shown to improve arterial oxygen tension. To test whether this improvement occurs over a specific range of variability, we examined several ventilation protocols in guinea pigs with endotoxin-induced lung injury. In Group I (n = 10), after 30 min of conventional volume-cycled ventilation, animals were ventilated with variable ventilation for 30-min intervals, during which time tidal volume was randomly varied by 10, 20, 40, and 60% of the mean, while simultaneously adjusting the frequency to maintain constant minute ventilation.