Sensitive physiological readouts to evaluate countermeasures for lipopolysaccharide-induced lung alterations in mice

Author:

Khadangi Fatemeh1,Tremblay-Pitre Sophie1,Dufour-Mailhot Alexis1,Rojas-Ruiz Andrés1,Boucher Magali1,Henry Cyndi1,Fereydoonzad Liah2,Brunet David2,Robichaud Annette2,Bossé Ynuk1ORCID

Affiliation:

1. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec, Quebec, Canada

2. SCIREQ – Scientific Respiratory Equipment Inc., Montreal, Quebec, Canada

Abstract

Despite decades of research, studies investigating the physiological alterations caused by an acute bout of inflammation induced by exposing the lung to lipopolysaccharide have yielded inconsistent results. This can be attributed to small effects and/or a lack of fitted physiological testing. Herein, a comprehensive investigation of lung mechanics was conducted on 270 male C57BL/6 mice at 24, 48, or 96 h after an intranasal exposure to saline or lipopolysaccharide at either 1 or 3 mg/kg (30 mice per group). Traditional techniques that probe the lung using small-amplitude perturbations (i.e., oscillometry) were used, together with less conventional and new techniques that probe the lung using maneuvers of large amplitudes. The latter include a partial and a full-range pressure-volume maneuvers to measure quasi-static elastance, compliance, total lung volume, vital capacity, and residual volume. The results demonstrate that lung mechanics assessed by oscillometry was only slightly affected by lipopolysaccharide, confirming previous findings. In contradistinction, lipopolysaccharide markedly altered mechanics when the lung was probed with maneuvers of large amplitudes. With the dose of 3 mg/kg at the peak of inflammation (48 h postexposure), lipopolysaccharide increased quasi-static elastance by 26.7% ( P < 0.0001) and decreased compliance by 34.5% ( P < 0.0001). It also decreased lung volumes, including total lung capacity, vital capacity, and residual volume by 33.3%, 30.5%, and 43.3%, respectively (all P < 0.0001). These newly reported physiological alterations represent sensitive outcomes to efficiently evaluate countermeasures (e.g., drugs) in the context of several lung diseases.

Funder

Fondation de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec

FRQ | Fonds de Recherche du Québec - Santé

Gouvernement du Canada | Canadian Institutes of Health Research

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada

Mitacs

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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