A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury

Enric Barbeta; Marta Arrieta; Ana Motos; Joaquim Bobi; Hua Yang; Minlan Yang; Giacomo Tanzella; Pierluigi Di Ginnatale; Stefano Nogas; Carmen Rosa Vargas; Roberto Cabrera; Denise Battaglini; Andrea Meli; Kasra Kiarostami; Nil Vázquez; Laia Fernández-Barat; Montserrat Rigol; Ricard Mellado-Artigas; Gerard Frigola; Marta Camprubí-Rimblas; Pau Ferrer; Daniel Martinez; Antonio Artigas; Carlos Ferrando; Miquel Ferrer; Antoni Torres

doi:10.1186/s13054-023-04512-8

A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury

Enric Barbeta, Marta Arrieta, Ana Motos^*, Joaquim Bobi, Hua Yang, Minlan Yang, Giacomo Tanzella, Pierluigi Di Ginnatale, Stefano Nogas, Carmen Rosa Vargas, Roberto Cabrera, Denise Battaglini, Andrea Meli, Kasra Kiarostami, Nil Vázquez, Laia Fernández-Barat, Montserrat Rigol, Ricard Mellado-Artigas, Gerard Frigola, Marta Camprubí-RimblasPau Ferrer, Daniel Martinez, Antonio Artigas, Carlos Ferrando, Miquel Ferrer, Antoni Torres^*

^*Corresponding author for this work

Cardiology

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

38 Downloads (Pure)

Abstract

Background:

Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia—the most common risk factor in humans—and analyze the additional effect of ventilator-induced lung injury (VILI).

Methods:

Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO₂/FiO₂ < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed.

Results:

All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO₂/FiO₂ was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage.

Conclusions:

In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.

Original language	English
Article number	239
Journal	Critical Care
Volume	27
Issue number	1
DOIs	https://doi.org/10.1186/s13054-023-04512-8
Publication status	Published - 16 Jun 2023

Bibliographical note

Funding Information:
MF received a grant from the Fondo de Investigación Sanitaria (PI18/00974), Instituto de Salud Carlos III, co-funded by the European Union, and a grant from SEPAR 2018. EB has received financial support from the Instituto de Salud Carlos III (Rio Hortega 2019: CM19/00133), co-funded by European Social Fund (ESF)/ “Investing in your future”, and the "Beca Becario" by SOCAP. CB06/06/0028/CIBER de enfermedades respiratorias- CIBERES, ICREA Academy/Institució Catalana de Recerca i Estudis Avançats, 2.603/IDIBAPS, SGR/Generalitat de Catalunya. Funders did not play any role in paper design, data collection, data analysis, interpretation, writing of the paper.

Funding Information:
We would like to thank Cristina Miralles who included and processed all of the histological samples. We would also like to thank Anthony Armenta for reviewing the English language and syntax used throughout the manuscript.

Publisher Copyright:
© 2023, The Author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s13054-023-04512-8Licence: CC BY

A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injuryFinal published version, 7.07 MBLicence: CC BY

Cite this

Barbeta, E., Arrieta, M., Motos, A., Bobi, J., Yang, H., Yang, M., Tanzella, G., Di Ginnatale, P., Nogas, S., Vargas, C. R., Cabrera, R., Battaglini, D., Meli, A., Kiarostami, K., Vázquez, N., Fernández-Barat, L., Rigol, M., Mellado-Artigas, R., Frigola, G., ... Torres, A. (2023). A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury. Critical Care, 27(1), Article 239. https://doi.org/10.1186/s13054-023-04512-8

@article{581fc7d0719349958b9dd4e8897cd389,

title = "A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury",

abstract = "Background: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia—the most common risk factor in humans—and analyze the additional effect of ventilator-induced lung injury (VILI). Methods: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. Results: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. Conclusions: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.",

author = "Enric Barbeta and Marta Arrieta and Ana Motos and Joaquim Bobi and Hua Yang and Minlan Yang and Giacomo Tanzella and \{Di Ginnatale\}, Pierluigi and Stefano Nogas and Vargas, \{Carmen Rosa\} and Roberto Cabrera and Denise Battaglini and Andrea Meli and Kasra Kiarostami and Nil V{\'a}zquez and Laia Fern{\'a}ndez-Barat and Montserrat Rigol and Ricard Mellado-Artigas and Gerard Frigola and Marta Camprub{\'i}-Rimblas and Pau Ferrer and Daniel Martinez and Antonio Artigas and Carlos Ferrando and Miquel Ferrer and Antoni Torres",

note = "Funding Information: MF received a grant from the Fondo de Investigaci{\'o}n Sanitaria (PI18/00974), Instituto de Salud Carlos III, co-funded by the European Union, and a grant from SEPAR 2018. EB has received financial support from the Instituto de Salud Carlos III (Rio Hortega 2019: CM19/00133), co-funded by European Social Fund (ESF)/ “Investing in your future”, and the {"}Beca Becario{"} by SOCAP. CB06/06/0028/CIBER de enfermedades respiratorias- CIBERES, ICREA Academy/Instituci{\'o} Catalana de Recerca i Estudis Avan{\c c}ats, 2.603/IDIBAPS, SGR/Generalitat de Catalunya. Funders did not play any role in paper design, data collection, data analysis, interpretation, writing of the paper. Funding Information: We would like to thank Cristina Miralles who included and processed all of the histological samples. We would also like to thank Anthony Armenta for reviewing the English language and syntax used throughout the manuscript. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jun,

day = "16",

doi = "10.1186/s13054-023-04512-8",

language = "English",

volume = "27",

journal = "Critical Care",

issn = "1364-8535",

publisher = "BioMed Central Ltd.",

number = "1",

}

Barbeta, E, Arrieta, M, Motos, A, Bobi, J, Yang, H, Yang, M, Tanzella, G, Di Ginnatale, P, Nogas, S, Vargas, CR, Cabrera, R, Battaglini, D, Meli, A, Kiarostami, K, Vázquez, N, Fernández-Barat, L, Rigol, M, Mellado-Artigas, R, Frigola, G, Camprubí-Rimblas, M, Ferrer, P, Martinez, D, Artigas, A, Ferrando, C, Ferrer, M & Torres, A 2023, 'A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury', Critical Care, vol. 27, no. 1, 239. https://doi.org/10.1186/s13054-023-04512-8

TY - JOUR

T1 - A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury

AU - Barbeta, Enric

AU - Arrieta, Marta

AU - Motos, Ana

AU - Bobi, Joaquim

AU - Yang, Hua

AU - Yang, Minlan

AU - Tanzella, Giacomo

AU - Di Ginnatale, Pierluigi

AU - Nogas, Stefano

AU - Vargas, Carmen Rosa

AU - Cabrera, Roberto

AU - Battaglini, Denise

AU - Meli, Andrea

AU - Kiarostami, Kasra

AU - Vázquez, Nil

AU - Fernández-Barat, Laia

AU - Rigol, Montserrat

AU - Mellado-Artigas, Ricard

AU - Frigola, Gerard

AU - Camprubí-Rimblas, Marta

AU - Ferrer, Pau

AU - Martinez, Daniel

AU - Artigas, Antonio

AU - Ferrando, Carlos

AU - Ferrer, Miquel

AU - Torres, Antoni

N1 - Funding Information: MF received a grant from the Fondo de Investigación Sanitaria (PI18/00974), Instituto de Salud Carlos III, co-funded by the European Union, and a grant from SEPAR 2018. EB has received financial support from the Instituto de Salud Carlos III (Rio Hortega 2019: CM19/00133), co-funded by European Social Fund (ESF)/ “Investing in your future”, and the "Beca Becario" by SOCAP. CB06/06/0028/CIBER de enfermedades respiratorias- CIBERES, ICREA Academy/Institució Catalana de Recerca i Estudis Avançats, 2.603/IDIBAPS, SGR/Generalitat de Catalunya. Funders did not play any role in paper design, data collection, data analysis, interpretation, writing of the paper. Funding Information: We would like to thank Cristina Miralles who included and processed all of the histological samples. We would also like to thank Anthony Armenta for reviewing the English language and syntax used throughout the manuscript. Publisher Copyright: © 2023, The Author(s).

PY - 2023/6/16

Y1 - 2023/6/16

N2 - Background: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia—the most common risk factor in humans—and analyze the additional effect of ventilator-induced lung injury (VILI). Methods: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. Results: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. Conclusions: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.

AB - Background: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia—the most common risk factor in humans—and analyze the additional effect of ventilator-induced lung injury (VILI). Methods: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. Results: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. Conclusions: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.

UR - http://www.scopus.com/inward/record.url?scp=85162719043&partnerID=8YFLogxK

U2 - 10.1186/s13054-023-04512-8

DO - 10.1186/s13054-023-04512-8

M3 - Article

C2 - 37328874

AN - SCOPUS:85162719043

SN - 1364-8535

VL - 27

JO - Critical Care

JF - Critical Care

IS - 1

M1 - 239

ER -

A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this