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Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury.

ABSTRACT: Mechanical ventilation of lungs suffering from microatelectases may trigger the development of acute lung injury (ALI). Direct lung injury by bleomycin results in surfactant dysfunction and microatelectases at day 1 while tissue elastance and oxygenation remain normal. Computational simulations of alveolar micromechanics 1-day post-bleomycin predict persisting microatelectases throughout the respiratory cycle and increased alveolar strain during low positive end-expiratory pressure (PEEP) ventilation. As such, we hypothesize that mechanical ventilation in presence of microatelectases, which occur at low but not at higher PEEP, aggravates and unmasks ALI in the bleomycin injury model. Rats were randomized and challenged with bleomycin (B) or not (H = healthy). One day after bleomycin instillation the animals were ventilated for 3 h with PEEP 1 (PEEP1) or 5 cmH2O (PEEP5) and a tidal volume of 10 ml/kg bodyweight. Tissue elastance was repetitively measured after a recruitment maneuver to investigate the degree of distal airspace instability. The right lung was subjected to bronchoalveolar lavage (BAL), the left lung was fixed for design-based stereology at light- and electron microscopic level. Prior to mechanical ventilation, lung tissue elastance did not differ. During mechanical ventilation tissue elastance increased in bleomycin-injured lungs ventilated with PEEP = 1 cmH2O but remained stable in all other groups. Measurements at the conclusion of ventilation showed the largest time-dependent increase in tissue elastance after recruitment in B/PEEP1, indicating increased instability of distal airspaces. These lung mechanical findings correlated with BAL measurements including elevated BAL neutrophilic granulocytes as well as BAL protein and albumin in B/PEEP1. Moreover, the increased septal wall thickness and volume of peri-bronchiolar-vascular connective tissue in B/PEEP1 suggested aggravation of interstitial edema by ventilation in presence of microatelectases. At the electron microscopic level, the largest surface area of injured alveolar epithelial was observed in bleomycin-challenged lungs after PEEP = 1 cmH2O ventilation. After bleomycin treatment cellular markers of endoplasmic reticulum stress (p-Perk and p-EIF-2?) were positive within the septal wall and ventilation with PEEP = 1 cmH2O ventilation increased the surface area stained positively for p-EIF-2?. In conclusion, hidden microatelectases are linked with an increased pulmonary vulnerability for mechanical ventilation characterized by an aggravation of epithelial injury.

SUBMITTER: Albert K

PROVIDER: S-EPMC7530907 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury.

Albert Karolin K Krischer Jeanne-Marie JM Pfaffenroth Alexander A Wilde Sabrina S Lopez-Rodriguez Elena E Braun Armin A Smith Bradford J BJ Knudsen Lars L

Frontiers in physiology 20200918

Mechanical ventilation of lungs suffering from microatelectases may trigger the development of acute lung injury (ALI). Direct lung injury by bleomycin results in surfactant dysfunction and microatelectases at day 1 while tissue elastance and oxygenation remain normal. Computational simulations of alveolar micromechanics 1-day post-bleomycin predict persisting microatelectases throughout the respiratory cycle and increased alveolar strain during low positive end-expiratory pressure (PEEP) ventil ...[more]

PMID: 33071807

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Project description:BackgroundPatients in intensive care units (ICUs) often received broad-spectrum antibiotic treatment and Acinetobacter baumannii (A.b.) and Pseudomonas aeruginosa (P.a.) were the most common pathogens causing ventilator-associated pneumonia (VAP). This study aimed to examine the effects and mechanism of mechanical ventilation (MV) on A.b.-induced lung injury and the involvement of alveolar macrophages (AMs).MethodsC57BL/6 wild-type (WT) and c-Jun N-terminal kinase knockout (JNK1-/-) mice received MV for 3 h at 2 days after nasal instillation of A.b., P.a. (1 × 106 colony-forming unit, CFU), or normal saline.ResultsIntranasal instillation of 106 CFU A.b. in C57BL/6 mice induced a significant increase in total cells and protein levels in the bronchoalveolar lavage fluid (BALF) and neutrophil infiltration in the lungs. MV after A.b. instillation increases neutrophil infiltration, interleukin (IL)-6 and vascular cell adhesion molecule (VCAM) mRNA expression in the lungs and total cells, IL-6 levels, and nitrite levels in the BALF. The killing activity of AMs against A.b. was lower than against P.a. The diminished killing activity was parallel with decreased tumor necrosis factor-α production by AMs compared with A.b. Inducible nitric oxide synthase inhibitor, S-methylisothiourea, decreased the total cell number in BALF on mice receiving A.b. instillation and ventilation. Moreover, MV decreased the A.b. and P.a. killing activity of AMs. MV after A.b. instillation induced less total cells in the BALF and nitrite production in the serum of JNK1-/- mice than those of WT mice.ConclusionA.b. is potent in inducing neutrophil infiltration in the lungs and total protein in the BALF. MV enhances A.b.-induced lung injury through an increase in the expression of VCAM and IL-6 levels in the BALF and a decrease in the bacteria-killing activity of AMs. A lower inflammation level in JNK1-/- mice indicates that A.b.-induced VAP causes lung injury through JNK signaling pathway in the lungs.

Project description:ObjectivesThe theoretical basis for minimizing tidal volume during high-frequency oscillatory ventilation may not be appropriate when lung tissue stretch occurs heterogeneously and/or rapidly. The objective of this study was to assess the extent to which increased ventilation heterogeneity may contribute to ventilator-induced lung injury during high-frequency oscillatory ventilation in adults compared with neonates on the basis of lung size, using a computational model of human lungs.DesignComputational modeling study.SettingResearch laboratory.SubjectsHigh-fidelity, 3D computational models of human lungs, scaled to various sizes representative of neonates, children, and adults, with varying injury severity. All models were generated from one thoracic CT image of a healthy adult male.InterventionsOscillatory ventilation was simulated in each lung model at frequencies ranging from 0.2 to 40 Hz. Sinusoidal flow oscillations were delivered at the airway opening of each model and distributed through the lungs according to regional parenchymal mechanics.Measurements and main resultsAcinar flow heterogeneity was assessed by the coefficient of variation in flow magnitudes across all acini in each model. High-frequency oscillatory ventilation simulations demonstrated increasing heterogeneity of regional parenchymal flow with increasing lung size, with decreasing ratio of deadspace to total acinar volume, and with increasing frequency above lung corner frequency and resonant frequency. Potential for resonant amplification was greatest in injured adult-sized lungs with higher regional quality factors indicating the presence of underdamped lung regions.ConclusionsThe potential for ventilator-induced lung injury during high-frequency oscillatory ventilation is enhanced at frequencies above lung corner frequency or resonant frequency despite reduced tidal volumes, especially in adults, due to regional amplification of heterogeneous flow. Measurements of corner frequency and resonant frequency should be considered during high-frequency oscillatory ventilation management.

Project description:In 1967, the term "respirator lung" was coined to describe the diffuse alveolar infiltrates and hyaline membranes that were found on postmortem examination of patients who had undergone mechanical ventilation.This mechanical ventilation can aggravate damaged lungs and damage normal lungs. In recent years, Various ventilation strategies have been used to minimize lung injury, including low tide volume, higher PEEPs, recruitment maneuvers and high-frequency oscillatory ventilation. which have been proved to reduce the occurrence of lung injury. In 2012,Needham et al. proposed a kind of lung protective mechanical ventilation, and their study showed that limited volume and pressure ventilation could significantly improve the 2-year survival rate of patients with acute lung injury.Volume controlled ventilation is the most commonly used method in clinical surgery at present.Volume controlled ventilation(VCV) is a time-cycled, volume targeted ventilation mode, ensures adequate gas exchange. Nevertheless, during VCV, airway pressure is not controlled.Pressure controlled ventilation（PCV） can ensure airway pressure,however minute ventilation is not guaranteed.Pressure controlled ventilation-volume guarantee(PCV-VG) is an innovative mode of ventilation utilizes a decelerating flow and constant pressure. Ventilator parameters are automatically changed with each patient breath to offer the target VT without increasing airway pressures. So PCV-VG has the advantages of both VCV and PCV to preserve the target minute ventilation whilst producing a low incidence of barotrauma pressure-targeted ventilation. Current studies on PCV-VG mainly focus on thoracic surgery, bariatric surgery and urological surgery, and the research indicators mainly focus on changes in airway pressure and intraoperative oxygenation index.The age of patients undergoing laparoscopic colorectal cancer resection is generally higher, the cardiopulmonary reserve function is decreased, and the influence of intraoperative pneumoperitoneum pressure and low head position increases the incidence of intraoperative and postoperative pulmonary complications.Whether PCV-VG can reduce the incidence of intraoperative lung injury and postoperative pulmonary complications in elderly patients undergoing laparoscopic colorectal cancer resection, and thereby improve postoperative recovery of these patients is still unclear.

Project description:BACKGROUND:The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. METHODS:Pregnant ewes (n?=?18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n?=?6), or were ventilated using an injurious high VT strategy (LPSINJ; n?=?5) or a protective ventilation strategy (LPSPROT; n?=?7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. RESULTS:LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. CONCLUSIONS:Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.

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Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury.

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Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury.

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