A novel swine model of the acute respiratory distress syndrome using clinically relevant injury exposures

Mohamad H Tiba; Brendan M McCracken; Danielle C Leander; Carmen I Colmenero; Jean A Nemzek; Michael W Sjoding; Kristine E Konopka; Thomas L Flott; J Scott VanEpps; Rodney C Daniels; Kevin R Ward; Kathleen A Stringer; Robert P Dickson

doi:10.14814/phy2.14871

A novel swine model of the acute respiratory distress syndrome using clinically relevant injury exposures

Physiol Rep. 2021 May;9(9):e14871. doi: 10.14814/phy2.14871.

Authors

Mohamad H Tiba^{1

2}, Brendan M McCracken^{1

2}, Danielle C Leander^{1

2}, Carmen I Colmenero^{1

2}, Jean A Nemzek^{2

3}, Michael W Sjoding^{2

4

5

6}, Kristine E Konopka^{2

7}, Thomas L Flott^{2

8}, J Scott VanEpps^{1

2

9

10}, Rodney C Daniels^{2

9

11}, Kevin R Ward^{1

2

9}, Kathleen A Stringer^{2

4

8}, Robert P Dickson^{2

4

12}

Affiliations

¹ Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA.
² Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, MI, USA.
³ Unit of Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁴ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁵ Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
⁹ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
¹¹ Department of Pediatrics, Pediatric Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
¹² Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, USA.

Abstract

To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high-fidelity swine model of ARDS utilizing clinically relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: (1) Indirect lung injury only: animals were inoculated by direct injection of Escherichia coli into the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; (2) Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope-delivered gastric particles; (3) Combined indirect and direct lung injury: animals were administered both above-described indirect and direct lung injury exposures. Animals were monitored for up to 12 h, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired postmortem for pathological examination. In contrast to indirect lung injury only and direct lung injury only groups, animals in the combined indirect and direct lung injury group exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO₂ /FiO₂ ratio 124.8 ± 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS and fills a crucial gap in the translational study of human lung injury.

Keywords: acute lung injury; acute respiratory distress syndrome; critical care; diffuse alveolar damage; direct lung injury; indirect lung injury; porcine models; sepsis; septic shock.

Publication types

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

MeSH terms

Animals
Disease Models, Animal*
Escherichia coli / pathogenicity
Lung / microbiology
Lung / pathology
Lung / physiopathology
Male
Pulmonary Gas Exchange
Respiratory Distress Syndrome / microbiology
Respiratory Distress Syndrome / pathology*
Respiratory Distress Syndrome / physiopathology
Swine

Abstract

Publication types

MeSH terms

Grants and funding