scholarly journals New Frontiers in Functional and Molecular Imaging of the Acutely Injured Lung: Pathophysiological Insights and Research Applications

2021 ◽  
Vol 12 ◽  
Author(s):  
Guido Musch

This review focuses on the advances in the understanding of the pathophysiology of ventilator-induced and acute lung injury that have been afforded by technological development of imaging methods over the last decades. Examples of such advances include the establishment of regional lung mechanical strain as a determinant of ventilator-induced lung injury, the relationship between alveolar recruitment and overdistension, the regional vs. diffuse nature of pulmonary involvement in acute respiratory distress syndrome (ARDS), the identification of the physiological determinants of the response to recruitment interventions, and the pathophysiological significance of metabolic alterations in the acutely injured lung. Taken together, these advances portray multimodality imaging as the next frontier to both advance knowledge of the pathophysiology of these conditions and to tailor treatment to the individual patient’s condition.

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Jon Petur Joelsson ◽  
Saevar Ingthorsson ◽  
Jennifer Kricker ◽  
Thorarinn Gudjonsson ◽  
Sigurbergur Karason

AbstractVentilator-induced lung injury (VILI) is a serious acute injury to the lung tissue that can develop during mechanical ventilation of patients. Due to the mechanical strain of ventilation, damage can occur in the bronchiolar and alveolar epithelium resulting in a cascade of events that may be fatal to the patients. Patients requiring mechanical ventilation are often critically ill, which limits the possibility of obtaining patient samples, making VILI research challenging. In vitro models are very important for VILI research, but the complexity of the cellular interactions in multi-organ animals, necessitates in vivo studies where the mouse model is a common choice. However, the settings and duration of ventilation used to create VILI in mice vary greatly, causing uncertainty in interpretation and comparison of results. This review examines approaches to induce VILI in mouse models for the last 10 years, to our best knowledge, summarizing methods and key parameters presented across the studies. The results imply that a more standardized approach is warranted.


2020 ◽  
Author(s):  
Sang Hoon Lee ◽  
Mi Hwa Shin ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Kyung Soo Chung ◽  
...  

Abstract BackgroundFor patients with acute respiratory distress syndrome (ARDS), a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 in lung injury using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model.MethodsWild-type male C57BL/6J mice and NOX4 KO male mice were divided into five groups: (1) control group: wild-type (WT) mice + non-ventilator; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group: NOX4 KO + non-ventilator; (4) NOX4 KO with HTV group: NOX4 KO mice + HTV; (5) NOX4 inhibitor group: WT mice + HTV + post-treatment (anti-GKT 137831 inhibitor). In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.ResultsCell counts from BALFs were significantly lower (p<0.01) in the NOX4 KO with HTV group compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO mouse group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (both, p<0.001). In patients with respiratory disease, NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit.ConclusionsIn the VILI model, NOX4 expression is significantly associated with Eph-ephrin signaling. It may be possible to block VILI using NOX4 antibodies.


2020 ◽  
Vol 318 (3) ◽  
pp. L494-L499 ◽  
Author(s):  
Seiha Yen ◽  
Melissa Preissner ◽  
Ellen Bennett ◽  
Stephen Dubsky ◽  
Richard Carnibella ◽  
...  

Both overdistension and atelectasis contribute to lung injury and mortality during mechanical ventilation. It has been proposed that combinations of tidal volume and end-expiratory lung volume exist that minimize lung injury linked to mechanical ventilation. The aim of this study was to examine this at the regional level in the healthy and endotoxemic lung. Adult female BALB/c mice were injected intraperitoneally with 10 mg/kg lipopolysaccharide (LPS) in saline or with saline alone. Four hours later, mice were mechanically ventilated for 2 h. Regional specific end-expiratory volume (sEEV) and tidal volume (sVt) were measured at baseline and after 2 h of ventilation using dynamic high-resolution four-dimensional computed tomography images. The regional expression of inflammatory genes was quantified by quantitative PCR. There was a heterogenous response in regional sEEV whereby endotoxemia increased gas trapping at end-expiration in some lung regions. Within the healthy group, there was a relationship between sEEV, sVt, and the expression of Tnfa, where high Vt in combination with high EEV or very low EEV was associated with an increase in gene expression. In endotoxemia there was an association between low sEEV, particularly when this was combined with moderate sVt, and high expression of IL6. Our data suggest that preexisting systemic inflammation modifies the relationship between regional lung volumes and inflammation and that although optimum EEV-Vt combinations to minimize injury exist, further studies are required to identify the critical inflammatory mediators to assess and the effect of different injury types on the response.


2014 ◽  
Vol 307 (1) ◽  
pp. L27-L37 ◽  
Author(s):  
Hannah T. Nickles ◽  
Migle Sumkauskaite ◽  
Xin Wang ◽  
Ingmar Wegner ◽  
Michael Puderbach ◽  
...  

The pathogenesis of ventilator-induced lung injury has predominantly been attributed to overdistension or mechanical opening and collapse of alveoli, whereas mechanical strain on the airways is rarely taken into consideration. Here, we hypothesized that mechanical ventilation may cause significant airway distension, which may contribute to the pathological features of ventilator-induced lung injury. C57BL/6J mice were anesthetized and mechanically ventilated at tidal volumes of 6, 10, or 15 ml/kg body wt. Mice were imaged by flat-panel volume computer tomography, and central airways were segmented and rendered in 3D for quantitative assessment of airway distension. Alveolar distension was imaged by intravital microscopy. Functional dead space was analyzed in vivo, and proinflammatory cytokine release was analyzed in isolated, ventilated tracheae. CT scans revealed a reversible, up to 2.5-fold increase in upper airway volume during mechanical ventilation compared with spontaneous breathing. Airway distension was most pronounced in main bronchi, which showed the largest volumes at tidal volumes of 10 ml/kg body wt. Conversely, airway distension in segmental bronchi and functional dead space increased almost linearly, and alveolar distension increased even disproportionately with higher tidal volumes. In isolated tracheae, mechanical ventilation stimulated the release of the early-response cytokines TNF-α and IL-1β. Mechanical ventilation causes a rapid, pronounced, and reversible distension of upper airways in mice that is associated with an increase in functional dead space. Upper airway distension is most pronounced at moderate tidal volumes, whereas higher tidal volumes redistribute preferentially to the alveolar compartment. Airway distension triggers proinflammatory responses and may thus contribute relevantly to ventilator-induced pathologies.


Author(s):  
Brynne D. Ovalle ◽  
Rahul Chakraborty

This article has two purposes: (a) to examine the relationship between intercultural power relations and the widespread practice of accent discrimination and (b) to underscore the ramifications of accent discrimination both for the individual and for global society as a whole. First, authors review social theory regarding language and group identity construction, and then go on to integrate more current studies linking accent bias to sociocultural variables. Authors discuss three examples of intercultural accent discrimination in order to illustrate how this link manifests itself in the broader context of international relations (i.e., how accent discrimination is generated in situations of unequal power) and, using a review of current research, assess the consequences of accent discrimination for the individual. Finally, the article highlights the impact that linguistic discrimination is having on linguistic diversity globally, partially using data from the United Nations Educational, Scientific and Cultural Organization (UNESCO) and partially by offering a potential context for interpreting the emergence of practices that seek to reduce or modify speaker accents.


2003 ◽  
Vol 9 (3) ◽  
pp. 343-362 ◽  
Author(s):  
A ADAMS ◽  
D SIMONSON ◽  
D DRIES

2019 ◽  
Vol 63 (3) ◽  
pp. 115-128 ◽  
Author(s):  
Maie Stein ◽  
Sylvie Vincent-Höper ◽  
Nicole Deci ◽  
Sabine Gregersen ◽  
Albert Nienhaus

Abstract. To advance knowledge of the mechanisms underlying the relationship between leadership and employees’ well-being, this study examines leaders’ effects on their employees’ compensatory coping efforts. Using an extension of the job demands–resources model, we propose that high-quality leader–member exchange (LMX) allows employees to cope with high job demands without increasing their effort expenditure through the extension of working hours. Data analyses ( N = 356) revealed that LMX buffers the effect of quantitative demands on the extension of working hours such that the indirect effect of quantitative demands on emotional exhaustion is only significant at low and average levels of LMX. This study indicates that integrating leadership with employees’ coping efforts into a unifying model contributes to understanding how leadership is related to employees’ well-being. The notion that leaders can affect their employees’ use of compensatory coping efforts that detract from well-being offers promising approaches to the promotion of workplace health.


Crisis ◽  
2016 ◽  
Vol 37 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Meshan Lehmann ◽  
Matthew R. Hilimire ◽  
Lawrence H. Yang ◽  
Bruce G. Link ◽  
Jordan E. DeVylder

Abstract. Background: Self-esteem is a major contributor to risk for repeated suicide attempts. Prior research has shown that awareness of stigma is associated with reduced self-esteem among people with mental illness. No prior studies have examined the association between self-esteem and stereotype awareness among individuals with past suicide attempts. Aims: To understand the relationship between stereotype awareness and self-esteem among young adults who have and have not attempted suicide. Method: Computerized surveys were administered to college students (N = 637). Linear regression analyses were used to test associations between self-esteem and stereotype awareness, attempt history, and their interaction. Results: There was a significant stereotype awareness by attempt interaction (β = –.74, p = .006) in the regression analysis. The interaction was explained by a stronger negative association between stereotype awareness and self-esteem among individuals with past suicide attempts (β = –.50, p = .013) compared with those without attempts (β = –.09, p = .037). Conclusion: Stigma is associated with lower self-esteem within this high-functioning sample of young adults with histories of suicide attempts. Alleviating the impact of stigma at the individual (clinical) or community (public health) levels may improve self-esteem among this high-risk population, which could potentially influence subsequent suicide risk.


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