ARDS is a common, severe surgical complication associated with atelectasis, pneumonia, and lung injury following operation, sepsis, trauma, and burns. Perfluorocarbons are inert, colorless, high-density, low surface tension liquids which carry large quantities of oxygen and carbon dioxide. Gas exchange may be successfully carried out during partial liquid ventilation (PLV, gas ventilation of the perfluorocarbon- filled lungs). In fact, gas exchange and pulmonary function appear to be enhanced during partial liquid when compared to gas ventilation in the setting of respiratory failure. The principal investigator has been performing studies in liquid ventilation over the last 4 years aid is currently evaluating clinical application of PLV in adult, pediatric, and neonatal patients. Through our laboratory effort, we have generated data which demonstrate the efficacy of PLV in improving gas exchange, pulmonary function, and oxygen delivery, as well as in reducing acute lung injury. The current research proposal is directed at investigating the mechanisms of improvement in pulmonary gas exchange previously demonstrated with PLV. Our investigation will assess potential changes in ventilation/perfusion matching and lung injury which would enhance gas exchange during PLV. We plan to initially perform computed tomographic imaging and measurements of functional residual capacity with PLV or gas ventilation in our oleic acid lung injury model. This will allow us to evaluate the role that perfluorocarbon distribution and alveolar recruitment play in enhancing gas exchange during PLV in the setting of respiratory failure. Secondly, we intend to investigate the effect of positron emission tomography- determined pulmonary, blood flow redistribution upon gas exchange-during PLV. Finally, we plan to assess the protective effects of PLV upon acute parameters of lung injury such as pulmonary capillary permeability, degree of intra-alveolar hemorrhage, and level of neutrophil infiltration and the relationship of these acute parameters to chronic markers of lung injury such as pulmonary compliance, degree of fibrosis, morphometrically- assessed lung parenchymal injury, and survival in a chronic rabbit lung injury model. A thorough understanding of these mechanisms will be critical to the clinical application of this new technology.
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