RHEOLOGICAL BEHAVIOR OF DSPC-, DBPC-, AND DPPC-OXYGEN MICROBUBBLES AND THEIR EFFECTIVENESS IN IMPROVING SURVIVAL IN A RAT MODEL OF LIPOPOLYSACCHARIDE-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME

Authors

Riaz Ur Rehman Mohammed, University of Nebraska-LincolnFollow

First Advisor

Dr. Benjamin S. Terry

Date of this Version

5-2022

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: Biomedical Engineering, Under the Supervision of Professor Benjamin S. Terry. Lincoln, Nebraska: May, 2022

Copyright © 2022 MOHAMMED RIAZ UR REHMAN

Abstract

Acute respiratory distress syndrome (ARDS) causes 75,000 deaths in the U.S., annually. It is characterized by hypoxemia and damage to the lung alveoli. ARDS Management strategies involve extracorporeal membrane oxygenation (ECMO) and mechanical ventilation, but none of these methods improve the mortality rates. Oxygen microbubbles (OMBs) consist of a lipid shell with an oxygen core and have potential to augment oxygenation to manage ARDS. Previous studies demonstrated significant improvements in systemic oxygenation and mortality upon administering OMBs.

We replicated an ARDS rat model by intratracheal administration of lipopolysaccharide at a 24 mg/kg dose. After inducing the disease in rats, the distearoylphosphatidylcholine (DSPC), dibehenoylphosphatidylcholine (DBPC), or dipalmitoylphosphatidylcholine (DPPC) OMBs were administered intraperitoneally at a 100 mL/kg dose every 12 h, up to 36 h. Arterial blood gas analysis and pulse oximetry were then performed. Results showed 77.8%, 20%, and 10% survival in the DSPC, DBPC, and DPPC groups. Rats in the first group had significantly greater survival than others. Beyond 12 hours, the mean %SpO2 and PaO2 of rats was greater in the DSPC group. Additionally, the mean edema score, wet/dry ratio, and inflammation scores were lower in the DSPC group.

The rheological behavior was characterized using a rotating rheometer. The oxygen microbubbles showed a shear-thinning behavior. The results also showed that the viscosity decreased with a decreasing volume fraction and increasing temperature. Lipids with longer chain lengths showed greater viscosities and greater storage and loss moduli. The viscoelastic behavior at lower angular frequencies was predominantly viscous. At greater frequencies, the behavior was predominantly elastic. These results explain the behavior of OMBs when acted upon by a stress. Non-Newtonian fluid models (Casson, Herschell-Bulkley, Power-law) were fit to the shear stress-shear strain data and the R2 and best-fit parameters were obtained to assess the fit. The viscoelastic behavior provides insight into the structure, molecular weight, and temperature-dependent properties of a material.

Advisor: Benjamin S. Terry