Linking lung function to structural damage of alveolar epithelium in ventilator-induced lung injury

Abstract

Understanding how the mechanisms of ventilator-induced lung injury (VILI), namely atelectrauma and volutrauma, contribute to the failure of the blood-gas barrier and subsequent intrusion of edematous fluid into the airspace is essential for the design of mechanical ventilation strategies that minimize VILI. We ventilated mice with different combinations of tidal volume and positive end-expiratory pressure (PEEP) and linked degradation in lung function measurements to injury of the alveolar epithelium observed via scanning electron microscopy. Ventilating with both high inspiratory plateau pressure and zero PEEP was necessary to cause derangements in lung function as well as visually apparent physical damage to the alveolar epithelium of initially healthy mice. In particular, the epithelial injury was tightly associated with indicators of alveolar collapse. These results support the hypothesis that mechanical damage to the epithelium during VILI is at least partially attributed to atelectrauma-induced damage of alveolar type I epithelial cells.

Surfactant Protein B Deficiency Induced High Surface Tension: Relationship between Alveolar Micromechanics, Alveolar Fluid Properties and Alveolar Epithelial Cell Injury

“…In the present study, a complete denudation of the alveolar epithelial basal lamina was rarely observed and the main features related to injury were swelling and clearing of cytoplasmic ground substance, blebbing, and rupture of apical membranes (Figure 6). Among the structural parameters, the surface area of epithelial basal lamina covered by injured cells demonstrated a strong correlation with lung mechanical impairment, a finding which confirms observation in models of VILI where epithelial injury observed with scanning electron microscopy was strongly correlated with elastance [51]. Based on the presented data, the primary effects of induced SP-B deficiency are subtle alterations in alveolar micromechanics and alveolar epithelial injury that initially occur without abnormalities in the ultrastructural features of the alveolar fluid.…”

Three Alveolar Phenotypes Govern Lung Function in Murine Ventilator-Induced Lung Injury

“…The macroscale pressures and flows applied at the trachea during mechanical ventilation result in microscale parenchymal injury ( Dreyfuss and Saumon, 1998 ). The resulting ingress of protein-rich edema into the parenchymal airspace causes changes in alveolar dynamics at the microscale that are then reflected in macroscale alterations in lung function ( Hamlington et al, 2018b ). Macro- to micro-scale interactions in VILI thus take place in both directions, which we investigated by correlating VILI-induced changes in mouse lung microstructure to changes in lung function.…”

“…The mechanism for inactivation of the LA fraction is less clear and may very well be multifactorial. Airspace protein content is elevated ( Figure 8C ) due to alveolar surface damage ( Dreyfuss et al, 1988 ; Hamlington et al, 2018b ) and the resulting alveolocapillary leak ( Hamlington et al, 2018a ). Alveolar surface damage increases the BALF concentration of epithelial proteins such as E-cadherin while alveolocapillary leak accounts for the presence of serum proteins including albumin and immunoglobulin (IgG) in the BALF of mice ventilated under similar conditions ( Smith et al, 2017 ).…”

“…The mechanisms of VILI are well documented and include direct tissue injury from overdistension (volutrauma) ( Webb and Tierney, 1974 ; Hernandez et al, 1989 ) and the cyclic collapse and reopening of small airways and alveoli (atelectrauma) ( Muscedere et al, 1994 ). These injurious forces act at the microscale to damage the epithelial and endothelial cells that comprise the blood-gas barrier ( Dreyfuss and Saumon, 1998 ; Hamlington et al, 2018b ), allowing the ingress of proteinaceous edema into the distal airspace that is associated with changes in lung mechanics ( Hamlington et al, 2016a ).…”

Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury

“…Figures 2E,F illustrate the initial tissue elastance after recruitment manoeuvre, H1, as a function of time of mechanical ventilation during PEEP = 1 and 5 cmH 2 O ventilation. Changes in the first tissue elastance measurement after recruitment manoeuvre have been shown to correlate with the degree of alveolar epithelial injury based on quantitative ultrastructural data (Smith et al, 2017;Hamlington et al, 2018). During PEEP = 1 cmH 2 O ventilation the first tissue elastance after recruitment remained roughly stable in healthy lungs (H/PEEP1) but demonstrated a significant increase with time in the bleomycin challenged lungs (B/PEEP1) ( Figure 2E, bleomycin effect p = 0.003, time effect p < 0.001, interaction < 0.001).…”