In the acute respiratory distress syndrome (ARDS), inflammatory lung injury increases alveolar-capillary barrier permeability. Vascular liquid floods the airspace of the lungs and causes pulmonary edema. The airspace flooding pattern is spatially heterogeneous. Patients with ARDS are treated by mechanical ventilation, which improves gas exchange but causes additional mechanical injury to the lungs that escalates over time. In particular, alveolar septa located between aerated and flooded alveoli are a site of stress concentration and the magnitude of the stress concentration is proportional to the surface tension at the air-liquid interface in flooded alveoli. Mechanical ventilation cyclically increases surface tension, thus exacerbates the stress concentrations and causes injury in the form of a sustained increase in surface tension. The sustained increase in surface tension makes mechanical ventilation yet more injurious. Thus ventilation injury escalates, with positive feedback, over time. Working in a high tidal volume lung injury model in rats, we aim to test a surface tension-lowering compound as a means of reducing the escalation of ventilation injury and to investigate the mechanism through which the compound acts.
Acute respiratory distress syndrome patients are treated by mechanical ventilation, which assists oxygenation but at the same time injures or exacerbates injury of the lungs. This proposal aims to reduce ventilator-induced lung injury with a surface tension-lowering compound.
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