Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome
- PMID: 36065853
- PMCID: PMC9446406
- 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
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.
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
Conflict of interest statement
None.
Figures













References
-
- Bellani, G. , Laffey, J. G. , Pham, T. , Fan, E. , Brochard, L. , Esteban, A. , Gattinoni, L. , van Haren, F. , Larsson, A. , McAuley, D. , Ranieri, M. , Rubenfeld, G. , Thompson, B. T. , Wrigge, H. , Slutsky, A. S. , Pesenti, A. , & LUNG SAFE Investigators., ESICM Trials Group . (2016). Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. Journal of the American Medical Association, 315(8), 788–800. 10.1001/jama.2016.0291 - DOI - PubMed
-
- Borden, M. (2021). Colonic oxygen microbubble augment systemic oxygenation & CO2 removal in a porcine smoke in porcine smoke inhalation model of severe hypoxia. ARDS Drug Development. Summitted. https://ards‐summit.com/program/day‐two/ - PMC - PubMed
-
- Bozinovski, S. , Jones, J. , Beavitt, S.‐J. , Cook, A. D. , Hamilton, J. A. , & Anderson, G. P. (2004). Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM‐CSF via repression of TLR‐4. American Journal of Physiology. Lung Cellular and Molecular Physiology, 286(4), L877–L885. 10.1152/ajplung.00275.2003 - DOI - PubMed
-
- Brooks, D. , Barr, L. C. , Wiscombe, S. , McAuley, D. F. , Simpson, A. J. , & Rostron, A. J. (2020). Human lipopolysaccharide models provide mechanistic and therapeutic insights into systemic and pulmonary inflammation. European Respiratory Journal, 56(1), 1–20. 10.1183/13993003.01298-2019 - DOI - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical