Yalcin H C, Perry S F, Ghadiali S N
Dept. of Mechanical Engineering and Mechanics, Lehigh UNiversity, Rm. 265 Packard Lab, 19 Memorial Drive West, Bethlehem, PA 18015, USA.
J Appl Physiol (1985). 2007 Nov;103(5):1796-807. doi: 10.1152/japplphysiol.00164.2007. Epub 2007 Aug 2.
Recent advances in the ventilation of patients with acute respiratory distress syndrome (ARDS), including ventilation at low lung volumes, have resulted in a decreased mortality rate. However, even low-lung volume ventilation may exacerbate lung injury due to the cyclic opening and closing of fluid-occluded airways. Specifically, the hydrodynamic stresses generated during airway reopening may result in epithelial cell (EpC) injury. We utilized an in vitro cell culture model of airway reopening to investigate the effect of reopening velocity, airway diameter, cell confluence, and cyclic closure/reopening on cellular injury. Reopening dynamics were simulated by propagating a constant-velocity air bubble in an adjustable-height parallel-plate flow chamber. This chamber was occluded with different types of fluids and contained either a confluent or a subconfluent monolayer of EpC. Fluorescence microscopy was used to quantify morphological properties and percentage of dead cells under different experimental conditions. Decreasing channel height and reopening velocity resulted in a larger percentage of dead cells due to an increase in the spatial pressure gradient applied to the EpC. These results indicate that distal regions of the lung are more prone to injury and that rapid inflation may be cytoprotective. Repeated reopening events and subconfluent conditions resulted in significant cellular detachment. In addition, we observed a larger percentage of dead cells under subconfluent conditions. Analysis of this data suggests that in addition to the magnitude of the hydrodynamic stresses generated during reopening, EpC morphological, biomechanical, and microstructural properties may also be important determinants of cell injury.
急性呼吸窘迫综合征（ARDS）患者通气方面的最新进展，包括低肺容量通气，已使死亡率降低。然而，即使是低肺容量通气，也可能因液体阻塞气道的周期性开闭而加重肺损伤。具体而言，气道重新开放期间产生的流体动力应力可能导致上皮细胞（EpC）损伤。我们利用气道重新开放的体外细胞培养模型，研究重新开放速度、气道直径、细胞汇合度以及周期性闭合/重新开放对细胞损伤的影响。通过在可调节高度的平行板流动腔中传播恒速气泡来模拟重新开放动态。该流动腔用不同类型的液体阻塞，并含有汇合或亚汇合的EpC单层。使用荧光显微镜定量不同实验条件下的形态学特性和死细胞百分比。由于施加于EpC的空间压力梯度增加，降低通道高度和重新开放速度会导致更高比例的死细胞。这些结果表明，肺的远端区域更容易受到损伤，快速充气可能具有细胞保护作用。重复的重新开放事件和亚汇合条件导致明显的细胞脱离。此外，我们在亚汇合条件下观察到更高比例的死细胞。对这些数据的分析表明，除了重新开放期间产生的流体动力应力大小外，EpC的形态学、生物力学和微观结构特性也可能是细胞损伤的重要决定因素。
