Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome

Riaz Ur Rehman Mohammed; Nathaniel T Zollinger; Andrea R McCain; Roser Romaguera-Matas; Seth P Harris; Keely L Buesing; Mark A Borden; Benjamin S Terry

doi:10.14814/phy2.15451

Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome

Physiol Rep. 2022 Sep;10(17):e15451. doi: 10.14814/phy2.15451.

Authors

Riaz Ur Rehman Mohammed¹, Nathaniel T Zollinger¹, Andrea R McCain², Roser Romaguera-Matas², Seth P Harris³, Keely L Buesing⁴, Mark A Borden⁵, Benjamin S Terry^{1

6}

Affiliations

¹ Biomedical Engineering Program, Department of Mechanical and Material Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
² Institutional Animal Care Program, Office of Research & Economic Development, University of Nebraska - Lincoln, Lincoln, Nebraska, USA.
³ School of Veterinary Medicine and Biomedical Sciences, University of Nebraska - Lincoln Institute of Agriculture and Natural Resources, Lincoln, Nebraska, USA.
⁴ Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA.
⁵ Biomedical Engineering Program, University of Colorado, Boulder, Colorado, USA.
⁶ Department of Mechanical Engineering, Brigham Young University, Provo, Utah, USA.

Abstract

With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to-severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO₂ value dropped below 70 mmHg, the PaO₂ /FiO₂ ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to-severe ARDS with tachycardia. The SpO₂ and PaO₂ of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks.

Keywords: Berlin criteria; acute respiratory distress syndrome; intraperitoneal; intrathoracic; oxygenated microbubbles; peripheral oxygenation.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
COVID-19*
Humans
Lipopolysaccharides / toxicity
Microbubbles
Respiration, Artificial
Respiratory Distress Syndrome* / chemically induced
Respiratory Distress Syndrome* / therapy
Swine

Substances

Lipopolysaccharides