Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema

Abstract

BackgroundIn patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema.MethodsEmphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed.ResultsEmphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04).ConclusionsIn the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0107-0) contains supplementary material, which is available to authorized users.

Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats

“…The lungs and heart were removed en bloc . The left lung was frozen in liquid nitrogen and immersed in formaldehyde solution (4%), embedded in paraffin, cut longitudinally in the central zone by means of a microtome into three slices, each 4 μm thick, and stained with hematoxylin–eosin for histological analysis (Samary et al, 2015 ; Padilha et al, 2016 ). Photomicrographs at magnifications of ×100, ×200, and ×400 were obtained from eight nonoverlapping fields of view per section using a light microscope (Olympus BX51, Olympus Latin America Inc., Brazil).…”

Endotoxin-Induced Emphysema Exacerbation: A Novel Model of Chronic Obstructive Pulmonary Disease Exacerbations Causing Cardiopulmonary Impairment and Diaphragm Dysfunction

“…In the experimental model used herein, emphysema was induced by multiple instillations of PPE (Henriques et al, 2016; Padilha et al, 2016; Wierzchon et al, 2017). This model does not employ the primary disease-causing agent of COPD in humans, which is cigarette smoke.…”

“…On each lung electron microscopy image (20 fields of view/animal), the following alterations were analyzed: (1) alveolar wall disruption; (2) elastic fiber destruction; (3) neutrophil and macrophage infiltration; (4) detachment of type II epithelial cells (Rocha et al, 2017); (5) endothelial-cell damage (Antunes et al, 2014); and (6) interstitial edema. On each diaphragm electron microscopy image (20 fields/animal), the following changes were analyzed: disorganized I-band glycogen accumulation, thickened Z lines, and mitochondrial aggregates (Padilha et al, 2016). Pathologic findings were graded on a five-point, semiquantitative, severity-based scoring system as follows: 0 = normal lung parenchyma, 1 = changes in 1–25% of examined tissue, 2 = changes in 26–50% of examined tissue, 3 = changes in 51–75% of examined tissue, and 4 = changes in 76–100% of examined tissue of examined tissue (Antunes et al, 2014).…”

Variability in Tidal Volume Affects Lung and Cardiovascular Function Differentially in a Rat Model of Experimental Emphysema

“…To the best of our knowledge, this was the first investigation of the effects of different levels of V T variability on pulmonary and cardiovascular function, lung morphometry, and gene expression of markers of inflammation, surfactant proteins, epithelial cell damage, cell mechanical stress, and fibrogenesis in experimental emphysema. We chose the repeated intratracheal elastase instillation model because it reproduces important features of emphysema, including deterioration of respiratory system mechanics, airspace enlargement, and lung inflammation (Antunes and Rocco, 2011 ; Cruz et al, 2012 ; Henriques et al, 2016 ; Oliveira et al, 2016 ; Padilha et al, 2016 ; Rocha et al, 2017 ; Suki et al, 2017 ). Furthermore, multiple elastase instillations can lead to cardiorespiratory alterations (Antunes et al, 2014 ) that are consistent with cor pulmonale , including increased RV afterload (Henriques et al, 2016 ).…”