Does Increased Non-Linear Behavior Caused by Dynamic Variables Increase Ventilatory-Induced Lung Injury (VILI)?

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Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces within the lungs. As a result, the patients must be mechanically ventilated. However, the very act of using a positive pressure to inflate the lungs often creates further damage, either through repeated opening and closing of collapse tissue or through its over distension. Ventilatory-induced lung injury (VILI), in itself is estimated to contribute to ~30% of the mortality. The best way shown to minimize VILI is through the use of small programmed breaths so as not to overinflate the lungs while still allowing adequate gas exchanges, superimposed upon a background pressure, in order to pre-inflate the lungs and prevent them from repeatedly collapsing. A remaining problem is that just as a rubber band changes its elasticity as it is stretched, so too the lung changes its mechanical properties during distension. Moreover, the lung is considerably more complex since different regions have different elasticities, which change differentially as air flows in and out of them. Airflow in turn depends on regional differences in the location, size, and number of conducting airways. Indeed, we have recently shown for the first time that dynamic changes in lung mechanics may contribute to VILI in patients, despite the use of safe ventilation modalities. This application proposes to examine the extent to which dynamic changes in lung mechanic contribute to VILI in an animal model, as a prelude to more costly, large scale clinical trials aimed at improving mortality.