Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome
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 venti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-09-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15451 |
| _version_ | 1797397162220322816 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Riaz Ur Rehman Mohammed |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:06:00Z |
| format | Article |
| id | doaj.art-b99bc6827b2043d2868f0541282862b6 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-09T01:06:00Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-b99bc6827b2043d2868f0541282862b62023-12-11T09:36:42ZengWileyPhysiological Reports2051-817X2022-09-011017n/an/a10.14814/phy2.15451Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndromeRiaz Ur Rehman Mohammed0Nathaniel T. Zollinger1Andrea R. McCain2Roser Romaguera‐Matas3Seth P. Harris4Keely L. Buesing5Mark A. Borden6Benjamin S. Terry7Biomedical Engineering Program, Department of Mechanical and Material Engineering University of Nebraska‐Lincoln Lincoln Nebraska USABiomedical Engineering Program, Department of Mechanical and Material Engineering University of Nebraska‐Lincoln Lincoln Nebraska USAInstitutional Animal Care Program, Office of Research & Economic Development University of Nebraska – Lincoln Lincoln Nebraska USAInstitutional Animal Care Program, Office of Research & Economic Development University of Nebraska – Lincoln Lincoln Nebraska USASchool of Veterinary Medicine and Biomedical Sciences University of Nebraska – Lincoln Institute of Agriculture and Natural Resources Lincoln Nebraska USADepartment of Surgery University of Nebraska Medical Center Omaha Nebraska USABiomedical Engineering Program University of Colorado Boulder Colorado USABiomedical Engineering Program, Department of Mechanical and Material Engineering University of Nebraska‐Lincoln Lincoln Nebraska USAAbstract 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.https://doi.org/10.14814/phy2.15451acute respiratory distress syndromeBerlin criteriaintraperitonealintrathoracicoxygenated microbubblesperipheral oxygenation |
| spellingShingle | 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 Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome Physiological Reports acute respiratory distress syndrome Berlin criteria intraperitoneal intrathoracic oxygenated microbubbles peripheral oxygenation |
| title | Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome |
| title_full | Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome |
| title_fullStr | Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome |
| title_full_unstemmed | Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome |
| title_short | Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS‐induced acute respiratory distress syndrome |
| title_sort | testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of lps induced acute respiratory distress syndrome |
| topic | acute respiratory distress syndrome Berlin criteria intraperitoneal intrathoracic oxygenated microbubbles peripheral oxygenation |
| url | https://doi.org/10.14814/phy2.15451 |
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