Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation.

Leandro Da Silva Cândido,Aline Maria Dos Santos,Laisy Cristina De Paula,Thalles De Freitas Castro,Natália Alves De Matos,Guilherme De Paula Costa,Frank Silva Bezerra,André Talvani,Silvia Dantas Cangussú,Walter Araujo Zin,Víctor M Mendoza-Núñez

doi:10.1155/2021/5196896

Abstract

Mechanical ventilation (MV) is essential for the treatment of critical patients since it may provide a desired gas exchange. However, MV itself can trigger ventilator-associated lung injury in patients. We hypothesized that the mechanisms of lung injury through redox imbalance might also be associated with pulmonary inflammatory status, which has not been so far described. We tested it by delivering different tidal volumes to normal lungs undergoing MV. Healthy Wistar rats were divided into spontaneously breathing animals (control group, CG), and rats were submitted to MV (controlled ventilation mode) with tidal volumes of 4 mL/kg (MVG4), 8 mL/kg (MVG8), or 12 mL/kg (MVG12), zero end-expiratory pressure (ZEEP), and normoxia (FiO2 = 21%) for 1 hour. After ventilation and euthanasia, arterial blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for subsequent analysis. MVG12 presented lower PaCO2 and bicarbonate content in the arterial blood than CG, MVG4, and MVG8. Neutrophil influx in BALF and MPO activity in lung tissue homogenate were significantly higher in MVG12 than in CG. The levels of CCL5, TNF-α, IL-1, and IL-6 in lung tissue homogenate were higher in MVG12 than in CG and MVG4. In the lung parenchyma, the lipid peroxidation was more important in MVG12 than in CG, MVG4, and MVG8, while there was more protein oxidation in MVG12 than in CG and MVG4. The stereological analysis confirmed the histological pulmonary changes in MVG12. The association of controlled mode ventilation and high tidal volume, without PEEP and normoxia, impaired pulmonary histoarchitecture and triggered redox imbalance and lung inflammation in healthy adult rats.

Highlights

Mechanical ventilation (MV) is an important therapeutic tool to restore or improve gas exchange in patients with respiratory failure [1,2,3]
MVG12 animals presented pH, pCO2, and HCO3- significantly different from control group (CG) and MVG4 rats (Table 1): pH was higher in MVG12 than in CG, MVG4, and MVG8 rats (ANOVA; p < 0:0001); lower PCO2 and HCO3- values in MVG12 than in the remaining groups (ANOVA; p < 0:0001)
In MVG4, MVG8, and MVG12 groups, respiratory rate (RR) remained unaltered resulting in proportional increases in minute ventilation

Summary

Introduction

Mechanical ventilation (MV) is an important therapeutic tool to restore or improve gas exchange in patients with respiratory failure [1,2,3]. Most subjects recover quickly, resulting in weaning from the ventilator, it is estimated that between 4 and 13% of them require mechanical. MV can trigger ventilatorinduced lung injury (VILI), an iatrogenic harm to patients without previous pulmonary involvement that may contribute to mortality [8, 9]. Volutrauma potentially triggers VILI, because of excessively high tidal volumes, leading to lung injuries [10]. Neutrophils are the main leukocytes involved in acute lung injury and VILI [12], but it is not known whether once present and activated in the alveolar space, these cells can contribute to the production of inflammatory markers such as cytokines and reactive oxygen species [13]

Methods

Results

Conclusion