Mechanical & Materials Engineering, Department of
First Advisor
Benjamin S. Terry
Date of this Version
5-2017
Citation
Legband, Nathan D. (2017). Development of Peritoneal Microbubble Oxygenation as an Extrapulmonary Treatment for Hypoxia (Doctoral dissertation). University of Nebraska-Lincoln.
Abstract
Patients affected by a respiratory disease or injury experience a substantially impaired respiratory system and as a consequence are unable to obtain a sufficient amount of oxygen. Hypoxia can quickly result in developing permanent tissue damage or death. Currently, the medical methods of treating hypoxia are mechanical ventilation or extracorporeal membrane oxygenation. However, these treatments are ineffective in certain cases and possess significant additional risks including barotrauma, infection, hemorrhage, and thrombosis.
The extrapulmonary method of peritoneal oxygenation has been investigated by other research groups as a potential alternative to providing supplemental oxygen in hypoxic animals. In peritoneal oxygenation, the peritoneum, the serous membrane that lines the abdominal cavity and organs, functions as an interface for gas exchange. However, previous attempts using artificial perfluorocarbons and hemoglobin based oxygen carriers have demonstrated limited increase in oxygenation and substantial health concerns. In this work, peritoneal microbubble oxygenation (PMO) therapy has been investigated as a viable method for delivering supplemental oxygen to hypoxic patients with critical lung injury. PMO therapy is accomplished with a custom infusion device designed to safely deliver oxygen microbubbles (OMBs), an innovative oxygen carrier, into the abdomen.
Animal models of acute lung trauma and respiratory disease were used to validate PMO therapy. The first model was a small animal feasibility study where fatal hypoxia was induced by pneumothorax. The second model was asphyxia by tracheal occlusion to test PMO therapy in the most severe lung injury. When animals were infused with OMBs, the average survival times after the incidence of injury increased significantly. PMO treatment increased mean survival time in fatal pneumothorax by 650% and by 180% in asphyxia. Finally, a respiratory disease model was developed and characterized to replicate acute respiratory distress syndrome (ARDS) in rats. ARDS pathology was reproduced by aerosolizing an endotoxin, lipopolysaccharide, into the lungs to incite an antagonistic immune response. Additionally, delivering OMBs for prolonged PMO treatment to rats was facilitated by comparing the efficiencies of multiple catheters implanted into the peritoneal cavity. The ARDS and treatment model could then be used to evaluate PMO therapy and other new methods of supplemental oxygen delivery.
Advisor: Benjamin S. Terry
Comments
A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Mechanical Engineering and Applied Mechanics, Under the Supervision of Professor Benjamin S. Terry. Lincoln, Nebraska: May, 2017
Copyright (c) 2017 Nathan D. Legband