Treatment of a Rat Model of LPS-Induced ARDS via Peritoneal Perfusion of Oxygen Microbubbles

Abstract

Acute respiratory distress syndrome (ARDS) is a serious respiratory condition that occurs in approximately 10% of patients entering intensive care units around the world, affecting nearly 190,000 patients annually in the United States. Owing to the severity of the condition, conventional methods of oxygenation are often insufficient. However, current alternate methods of oxygenation are associated with contraindications and a mortality rate near 50%. Therefore, a need exists for a safer and more effective method of oxygenation for patients with ARDS. In this work, the feasibility of using intraperitoneal perfusions of oxygen microbubbles—peritoneal microbubble oxygenation (PMO)—to treat lipopolysaccharide-induced ARDS was explored with the objective of showing restoration of normoxic conditions after a single bolus infusion of oxygen microbubbles. Male Wistar rats induced with ARDS via lipopolysaccharide inhalation were treated with PMO at 12-h intervals over a period of 48 h. Their physiological responses were monitored throughout the study, after which necropsy was performed. Response data were then compared with saline control and untreated groups. We conclude that rats experiencing moderate to severe ARDS that were treated with PMO experienced a survival rate 37% higher than animals not given treatment and exhibited increased peripheral blood oxygen saturation when compared with untreated and saline-treated groups. Moreover, those treated with PMO experienced a lower lung wet/dry ratio and less severe lung pathology, indicating a surprising improvement in lung health. Overall, this study demonstrates the ability of PMO to deliver life-sustaining supplemental oxygen to rats suffering from ARDS and warrants further work toward clinical translation.