In Vitro Model of Stretch-Induced Lung Injury to Study Different Lung Ventilation Regimens and the Role of Sedatives

Abstract

Background: Currently lung injury is managed conservatively through supportive care including mechanical ventilation. However, mechanical ventilation can also cause additional lung injury due to over-stretch along with atelectasis and cytokine release. Here we developed an in vitro mechanical ventilation model using cyclic stretch of lung epithelial cells to mimic high and low tidal volume (TV) ventilation strategy, so that we could use this platform for pathophysiology analysis and screening for therapeutic drugs. Method:We subjected MLE-15 cells to the following treatments. 1) No treatment, 2) lipopolysaccharide (100 ng/mL) stimulation for 24 hours, 3) mechanical stretch initiated at 6-hour time point for 18 hours, 4) LPS stimulation at time point 0 hour, and mechanical stretch was added at 6-hour time point for 18 hours. Biaxial cyclic stretch with a triangular wave was given via the Flexcell FX-6000 tension system to mimic low and high TV. Anesthetics dexmedetomidine and propofol were also tested.Result: Our high TV mimic stretch increased cell death, while low TV mimic stretch did not affect the degree of cell death. Using this system, we examined the effect of sedatives commonly used in intensive care units on cell death and found that dexmedetomidine attenuated necrosis associated with stretch. Conclusion:We described the in vitro cyclic stretch system mimicking high and low TV ventilation. High TV mimetic was associated with increased cell death. Dexmedetomidine attenuated the degree of cell death.

Peptide-Functionalized Electrospun Meshes for the Physiological Cultivation of Pulmonary Alveolar Capillary Barrier Models in a 3D-Printed Micro-Bioreactor

“…Their results could successfully demonstrate that cyclic stretching of epithelial monolayers for only 2 h already causes increased cell layer permeability due to elevated levels of reactive oxygen species (ROS). Similar studies using a combination of biaxial strain and PDMS-based membrane systems focused on the effects of distention frequency, duration, and amplitude on epithelial cell layer permeability and viability or investigated the influence of sedatives on the epithelium during mechanical ventilation. − While all of these studies resulted in valuable scientific contributions regarding central biomedical challenges, the corresponding in vitro models are based on membrane systems that do not resemble the fibrous architecture of the natural BM and simplify cyclic stretching by applying either uni- or biaxial instead of physiological triaxial strain.…”