Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

Krischer, Jeanne-Marie; Albert, Karolin; Pfaffenroth, Alexander; López-Rodríguez, Elena; Ruppert, Clemens; Smith, Bradford J.; Knudsen, Lars

doi:10.1007/s00418-020-01938-x

Cited by 10 publications

(9 citation statements)

References 85 publications

(133 reference statements)

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“…Intracellular surfactant is released into the airspace, where it is essential for reducing surface tension at the alveolar air–liquid interface at end-expiration, so that it stabilizes the surface area available for gas-exchange throughout the respiratory cycle and reduces the inspiratory work load. Until week 8 of induction of Nedd4-2 deficiency, the intracellular surfactant pool, defined as the total amount of the lamellar bodies in AE2 cells [ 31 ], did not differ from age-matched controls, although the trafficking of prosurfactant protein C towards the lamellar bodies depends on Nedd4-2 . Accordingly, in our present study, neither the absolute volume of lamellar bodies in the lung nor the volume-weighted mean volume of lamellar bodies differed between Nedd4-2 -deficient and age-matched control groups.…”

Section: Discussionmentioning

confidence: 99%

Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2

Engelmann

Knudsen

Leitz

et al. 2021

IJMS

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Our previous study showed that in adult mice, conditional Nedd4-2-deficiency in club and alveolar epithelial type II (AE2) cells results in impaired mucociliary clearance, accumulation of Muc5b and progressive, terminal pulmonary fibrosis within 16 weeks. In the present study, we investigated ultrastructural alterations of the alveolar epithelium in relation to interstitial remodeling in alveolar septa as a function of disease progression. Two, eight and twelve weeks after induction of Nedd4-2 knockout, lungs were fixed and subjected to design-based stereological investigation at the light and electron microscopic level. Quantitative data did not show any abnormalities until 8 weeks compared to controls. At 12 weeks, however, volume of septal wall tissue increased while volume of acinar airspace and alveolar surface area significantly decreased. Volume and surface area of alveolar epithelial type I cells were reduced, which could not be compensated by a corresponding increase of AE2 cells. The volume of collagen fibrils in septal walls increased and was linked with an increase in blood–gas barrier thickness. A high correlation between parameters reflecting interstitial remodeling and abnormal AE2 cell ultrastructure could be established. Taken together, abnormal regeneration of the alveolar epithelium is correlated with interstitial septal wall remodeling.

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Section: Discussionmentioning

confidence: 99%

Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2

Engelmann

Knudsen

Leitz

et al. 2021

IJMS

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“…In a healthy lung, however, the pulmonary surfactant system not only reduces but also harmonizes surface tension in the alveoli, so that alveoli of different sizes can co-exist and stress concentration is avoided ( Schürch, 1982 ; Schirrmann et al, 2010 ). Low volume mechanical ventilation or spontaneous breathing in presence of stress concentrations, such as microatelectases or flooded alveoli, results in injury of the blood-gas barrier and degradation of lung mechanics, despite no increase in strain at the organ level ( Wu et al, 2014 ; Albert et al, 2020 ; Krischer et al, 2021 ; Bachmann et al, 2022 ). High tidal volume ventilation with low positive end-expiratory pressure produces progressive ventilation-induced lung injury with severe damage of the blood-gas barrier in mice ( Hamlington et al, 2018 ).…”

Section: Respiration Related Deformation Of the Lung Parenchyma: Visu...mentioning

confidence: 99%

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

et al. 2023

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Within the pulmonary acini ventilation and blood perfusion are brought together on a huge surface area separated by a very thin blood-gas barrier of tissue components to allow efficient gas exchange. During ventilation pulmonary acini are cyclically subjected to deformations which become manifest in changes of the dimensions of both alveolar and ductal airspaces as well as the interalveolar septa, composed of a dense capillary network and the delicate tissue layer forming the blood-gas barrier. These ventilation-related changes are referred to as micromechanics. In lung diseases, abnormalities in acinar micromechanics can be linked with injurious stresses and strains acting on the blood-gas barrier. The mechanisms by which interalveolar septa and the blood-gas barrier adapt to an increase in alveolar volume have been suggested to include unfolding, stretching, or changes in shape other than stretching and unfolding. Folding results in the formation of pleats in which alveolar epithelium is not exposed to air and parts of the blood-gas barrier are folded on each other. The opening of a collapsed alveolus (recruitment) can be considered as an extreme variant of septal wall unfolding. Alveolar recruitment can be detected with imaging techniques which achieve light microscopic resolution. Unfolding of pleats and stretching of the blood-gas barrier, however, require electron microscopic resolution to identify the basement membrane. While stretching results in an increase of the area of the basement membrane, unfolding of pleats and shape changes do not. Real time visualization of these processes, however, is currently not possible. In this review we provide an overview of septal wall micromechanics with focus on unfolding/folding as well as stretching. At the same time we provide a state-of-the-art design-based stereology methodology to quantify microarchitecture of alveoli and interalveolar septa based on different imaging techniques and design-based stereology.

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“… alveolar mechanical stress defined by deformation and increased pressure on the epithelial cells (AEC) caused by mechanical ventilation, dysregulated inflammatory responses in the alveola with activation of coagulation system, leucocytes and platelets, activation of ECs and increased capillary permeability due to endogenous inflammatory mediators and/or exogenous toxic products, alveolar surfactant deactivation due to ventilatory-stretch and deformation of AEC type II cells. [ 26 ] increased hydrostatic capillary pressure due to cardiogenic failure or fluid overload. …”

Section: Post-thoracotomy Respiratory Failure and Acute Lung Isnjurymentioning

confidence: 99%

“…alveolar surfactant deactivation due to ventilatory-stretch and deformation of AEC type II cells. [ 26 ]…”

Section: Post-thoracotomy Respiratory Failure and Acute Lung Isnjurymentioning

confidence: 99%

Restricted, optimized or liberal fluid strategy in thoracic surgery

Licker

Hagerman

Bédat

et al. 2021

Saudi Journal of Anaesthesia

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Perioperative fluid balance has a major impact on clinical and functional outcome, regardless of the type of interventions. In thoracic surgery, patients are more vulnerable to intravenous fluid overload and to develop acute respiratory distress syndrome and other complications. New insight has been gained on the mechanisms causing pulmonary complications and the role of the endothelial glycocalix layer to control fluid transfer from the intravascular to the interstitial spaces and to promote tissue blood flow. With the implementation of standardized processes of care, the preoperative fasting period has become shorter, surgical approaches are less invasive and patients are allowed to resume oral intake shortly after surgery. Intraoperatively, body fluid homeostasis and adequate tissue oxygen delivery can be achieved using a normovolemic therapy targeting a “near-zero fluid balance” or a goal-directed hemodynamic therapy to maximize stroke volume and oxygen delivery according to the Franck–Starling relationship. In both fluid strategies, the use of cardiovascular drugs is advocated to counteract the anesthetic-induced vasorelaxation and maintain arterial pressure whereas fluid intake is limited to avoid cumulative fluid balance exceeding 1 liter and body weight gain (~1-1.5 kg). Modern hemodynamic monitors provide valuable physiological parameters to assess patient volume responsiveness and circulatory flow while guiding fluid administration and cardiovascular drug therapy. Given the lack of randomized clinical trials, controversial debate still surrounds the issues of the optimal fluid strategy and the type of fluids (crystalloids versus colloids). To avoid the risk of lung hydrostatic or inflammatory edema and to enhance the postoperative recovery process, fluid administration should be prescribed as any drug, adapted to the patient's requirement and the context of thoracic intervention.

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Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

Cited by 10 publications

References 85 publications

Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2

Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

Restricted, optimized or liberal fluid strategy in thoracic surgery

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