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Linking lung function and inflammatory responses in ventilator-induced lung injury

Version 2 2024-06-13, 15:19
Version 1 2022-03-29, 16:00
journal contribution
posted on 2024-06-13, 15:19 authored by V Cannizzaro, Z Hantos, PD Sly, GR Zosky
Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

History

Journal

American Journal of Physiology - Lung Cellular and Molecular Physiology

Volume

300

Pagination

L112-L120

Location

United States

ISSN

1040-0605

eISSN

1522-1504

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

1

Publisher

AMER PHYSIOLOGICAL SOC