Normal lung mechanics maximize gas exchange across the alveolar-capillary membrane. However, pulmonary diseases such as Acute Respiratory Distress Syndrome (ARDS) disrupt this function by allowing edematous fluid from the vasculature to enter and occlude airways and alveoli. ARDS causes about 59,000 deaths per year in the United States with a mortality rate between 36.2 â"u20ac"u201c 44.3%. To improve gas exchange, patients are often treated with mechanical ventilation, which can cause atelectrauma during the recruitment and derecruitment of occluded airways and alveoli. Previous in vitro experiments have modeled the interfacial flow of airway recruitment by introducing a single finger of air into epithelial-lined parallel plate chambers and tubes. The objective of the current study is to longitudinally track the cellular injury and detachment associated with interfacial stresses that arise from 20 cycles of recruitment and derecruitment. We found that cellular injury trends asymptotically from 4.1% after one cycle to 11.2% after 20 cycles. In addition, we found that cellular detachment trends linearly from 0.0 to 6.4% over 20 cycles. The asymptotic behavior of cell damage agrees with conclusions of prior investigations and implies the existence of a â"u20ac˜critical numberâ"u20ac™ of bubble passes, above which no additional damage occurs. This cyclic recruitment and derecruitment model provides a platform for investigating the cellular biomechanics leading to epithelial injury during mechanical ventilation of patients with ARDS. / Thomas A Itin

archives@tulane.edu / Acute respiratory distress syndrome (ARDS) is a life-threatening, non-carcinogenic inflammatory pulmonary conditions characterized by the collection of fluids in the air sacs of the lungs. When fluid-filled airways are ventilated, the stresses of repetitive recruitment-decruitment (Rec-Der) causes cellular damage to the epithelial surface, leading to ventilator induced lung injury (VILI). The objective of this study was to establish a foundation for use of electric cell-substance impedance sensing (ECIS) in real-time analysis of cell membrane morphology and RecDer-induced damage. NCI H441 papillary adenocarcinoma human pulmonary epithelial cells are cultured onto custom 1F8x10E PC Flow Array. 10mM cysteine and 1% gelatin surface treatments demonstrated strong results for improved cell-substrate adhesion strength. RecDer insults were introduced at a velocity of 0.5mm/s through FBS-enhanced RPMI164 growth media. Experimental trials for 0 (n=1), 1 (n=1), 5 (n=1), 10 (n=1), 20 (n=7), and 50 (n=1) RecDer insults were analyzed using Annexin-V/PI flow cytometry; results showed monolayer health of 97.76%, 93.152%, 91.801%, 72.495%, 66.88% and 60.812% respectively. Trials for 20 (n=1), 30 (n=1), and 40 (n=1) RecDer insults were analyzed using ECIS; Frequency-dependent impedance modeling of the acquired data suggested increased damage to both cell-cell junction health and cell membrane integrity with increased RecDer insults. Results established a strong foundation for ECIS analysis of RecDer-induced monolayer damage. / 1 / Joshua Erwa Yao

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