Acute respiratory distress syndrome (ARDS) arising from trauma, sepsis, pneumonia or other diseases affects nearly 190,000 patients in the U.S. each year, and the mortality rate remains high at 35-40%. Currently, the last resort for treating ARDS, where mechanical ventilation has failed, is ECMO: a temporary, artificial, extracorporeal support of the respiratory system. Thrombosis and other significant safety complications are associated with extracorporeal membrane oxygenation (ECMO), and clinical trials of ECMO for the treatment of ARDS has shown limited efficacy. We propose to develop intraperitoneal membrane ventilation with oxygen microbubbles as a safe and effective alternative method for extra pulmonary oxygenation to treat these patients by providing essential systemic oxygen while allowing the lung injury to heal. Oxygen microbubbles are less expensive and have a higher oxygen carrier capacity than prior aqueous formulations of fluorocarbon emulsions and liposomal hemoglobin. Additionally, oxygen microbubbles provide an overall rate of oxygen transfer to the peritoneum that is at least three orders of magnitude higher than mechanical ventilation of the intraperitoneal cavity. Our preliminary data in a small animal model for ARDS shows that PMO is a promising therapy for severe hypoxemia. The proposed work will bring this technology closer to human translation by investigating its effectiveness for treating ARDS in large animals. The two specific aims of this proposal are to determine microbubble gas exchange transport properties in vitro, and to demonstrate microbubble peritoneal ventilation in vivo by use of an established ARDS animal model. The first working hypothesis is that circulating OMBs through the peritoneal cavity exchanges physiologically relevant levels of O2 for CO2. Therefore, the purpose of aim 1 is to determine the kinetics of gas exchange between OMBs and blood in a simple in vitro system. The second working hypothesis is that circulation of OMBs through the peritoneal cavity prevents hypoxia in a rat model of moderate to severe ARDS. Translation of our previously successful short-term use of this technology will require demonstration of successful oxygenation over a clinically relevant time period, therefore the activity for aim 2 is to evaluate oxygenation before, during, and after circulation of OMBs through the peritoneal cavity of the animal model. Relevance to Public Health: ARDS syndrome affects nearly 190,000 patients in the U.S. each year, and the mortality rate remains high at 40% owing to inadequate and injurious effects of mechanical ventilation. This project will develop and test peritoneal ventilation with oxygen microbubbles - an innovative extra pulmonary oxygenation technology - for the treatment of these patients.