scholarly journals Cytological analysis of the lung material of C57BL/6Y mice in the simulation of acute respiratory distress syndrome

Biomeditsina ◽  
2021 ◽  
Vol 17 (3E) ◽  
pp. 17-22
Author(s):  
O. V. Alimkina ◽  
A. E. Petrenko

The work is devoted to the study of changes in the cellular composition of bronchoalveolar lavage over time in the modeling of acute respiratory distress syndrome (ARDS) in mice. ARDS was modeled by administering α-galactosylceramide and a mixture of lipopolysaccharide with a complete Freud’s adjuvant. After euthanasia, bronchoalveolar lavage was taken for analysis. On this basis, changes in the total number of white blood cells, the percentage of neutrophils and macrophages were assessed. It was found that the percentage of neutrophils in the ARDS group shows a statistically significant difference from that in the intact group, starting from 3 hours after modeling ARDS. Further, a statistically significant decrease in macrophages was observed. 

Biomeditsina ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. 17-22
Author(s):  
O. V. Alimkina ◽  
A. E. Petrenko ◽  
E. S. Savchenko ◽  
N. S. Ogneva ◽  
L. A. Taboyakova ◽  
...  

This article investigates changes in the cellular composition of bronchoalveolar lavage over time in the modeling of acute respiratory distress syndrome (ARDS) in mice, followed by a single administration of Leutragine. In intact animals, macrophages predominate in bronchoalveolar lavage, which is the physiological norm. When modeling ARDS, neutrophils increase. A single administration of Leutragine leads to a significant reduction in the number of neutrophils and a simultaneous increase in macrophages in 72 hours, thus bringing the cellular composition of lavage to normal.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Asbjørn G. Petersen ◽  
Peter C. Lind ◽  
Anne-Sophie B. Jensen ◽  
Mark A. Eggertsen ◽  
Asger Granfeldt ◽  
...  

Abstract Background Senicapoc is a potent and selective blocker of KCa3.1, a calcium-activated potassium channel of intermediate conductance. In the present study, we investigated whether there is a beneficial effect of senicapoc in a large animal model of acute respiratory distress syndrome (ARDS). The primary end point was the PaO2/FiO2 ratio. Methods ARDS was induced in female pigs (42–49 kg) by repeated lung lavages followed by injurious mechanical ventilation. Animals were then randomly assigned to vehicle (n = 9) or intravenous senicapoc (10 mg, n = 9) and received lung-protective ventilation for 6 h. Results Final senicapoc plasma concentrations were 67 ± 18 nM (n = 9). Senicapoc failed to change the primary endpoint PaO2/FiO2 ratio (senicapoc, 133 ± 23 mmHg; vehicle, 149 ± 68 mmHg). Lung compliance remained similar in the two groups. Senicapoc reduced the level of white blood cells and neutrophils, while the proinflammatory cytokines TNFα, IL-1β, and IL-6 in the bronchoalveolar lavage fluid were unaltered 6 h after induction of the lung injury. Senicapoc-treatment reduced the level of neutrophils in the alveolar space but with no difference between groups in the cumulative lung injury score. Histological analysis of pulmonary hemorrhage indicated a positive effect of senicapoc on alveolar–capillary barrier function, but this was not supported by measurements of albumin content and total protein in the bronchoalveolar lavage fluid. Conclusions In summary, senicapoc failed to improve the primary endpoint PaO2/FiO2 ratio, but reduced pulmonary hemorrhage and the influx of neutrophils into the lung. These findings open the perspective that blocking KCa3.1 channels is a potential treatment to reduce alveolar neutrophil accumulation and improve long-term outcome in ARDS.


2020 ◽  
pp. 088506662094404
Author(s):  
Shubhi Kaushik ◽  
Sindy Villacres ◽  
Ruth Eisenberg ◽  
Shivanand S. Medar

Objectives: To describe the incidence of and risk factors for acute kidney injury (AKI) in children with acute respiratory distress syndrome (ARDS) and study the effect of AKI on patient outcomes. Design: A single-center retrospective study. Setting: A tertiary care children’s hospital. Patients: All patients less than 18 years of age who received invasive mechanical ventilation (MV) and developed ARDS between July 2010 and July 2013 were included. Acute kidney injury was defined using p-RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria. Interventions: None. Measurements and Main Results: One hundred fifteen children met the criteria and were included in the study. Seventy-four children (74/115, 64%) developed AKI. The severity of AKI was risk in 34 (46%) of 74, injury in 19 (26%) of 74, and failure in 21 (28%) of 74. The presence of AKI was associated with lower Pao 2 to Fio 2 (P/F) ratio ( P = .007), need for inotropes ( P = .003), need for diuretics ( P = .004), higher oxygenation index ( P = .03), higher positive end-expiratory pressure (PEEP; P = .01), higher mean airway pressure ( P = .008), and higher Fio 2 requirement ( P = .03). Only PEEP and P/F ratios were significantly associated with AKI in the unadjusted logistic regression model. Patients with AKI had a significantly longer duration of hospital stay, although there was no significant difference in the intensive care unit stay, duration of MV, and mortality. Recovery of AKI occurred in 68% of the patients. A multivariable model including PEEP, P/F ratio, weight, need for inotropes, and need for diuretics had a better receiver operating characteristic (ROC) curve with an AUC of 0.75 compared to the ROC curves for PEEP only and P/F ratio only for the prediction of AKI. Conclusions: Patients with ARDS have high rates of AKI, and its presence is associated with increased morbidity and mortality.


2020 ◽  
Author(s):  
Sheng-Yuan Ruan ◽  
Chun-Ta Huang ◽  
Ying-Chun Chien ◽  
Chun-Kai Huang ◽  
Jung-Yien Chien ◽  
...  

Abstract Background: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.Methods: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. Results: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.Conclusion: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2015 ◽  
Author(s):  
Isabel Tovar ◽  
Rosa Guerrero ◽  
Jesús J. López-Peñalver ◽  
José Expósito ◽  
José Mariano Ruiz de Almodóvar

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients’ respiratory capacity and increase the expectations of their cure.


2019 ◽  
Vol 130 (3) ◽  
pp. 404-413 ◽  
Author(s):  
Tim Rahmel ◽  
Katharina Rump ◽  
Jürgen Peters ◽  
Michael Adamzik

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The aquaporin-5 (AQP5) –1364A/C promoter single-nucleotide polymorphism is associated with an altered AQP5 expression and mortality in sepsis. Because AQP5 expression alters neutrophil cell migration, it could affect pulmonary inflammation and survival in bacterially evoked acute respiratory distress syndrome. Accordingly, the authors tested the hypotheses that the AC/CC genotype in patients with bacterially evoked pneumonia resulting in acute respiratory distress syndrome is associated with (1) attenuated pulmonary inflammation and (2) higher 30-day survival. Methods In this prospective, observational study, bronchoalveolar lavage and blood sampling were performed within 24 h of intensive care unit admission. In 136 Caucasian patients with bacterially evoked acute respiratory distress syndrome, genotype of the AQP5 –1364A/C promoter polymorphism, bronchoalveolar lavage total protein, albumin, white cell concentrations, and lactate dehydrogenase activity were measured to evaluate the relationship between genotypes and survival. Results AC/CC patients as well as survivors showed lower bronchoalveolar lavage protein (0.9 mg/ml vs. 2.3 mg/ml, P &lt; 0.001 and 1.6 mg/ml vs. 2.6 mg/ml, P = 0.035), albumin (0.2 mg/ml vs. 0.6 mg/ml, P = 0.019 and 0.3 mg/ml vs. 0.6 mg/ml, P = 0.028), leukocytes (424 /ml vs. 1,430/ml; P = 0.016 and 768 /ml vs. 1,826/ml; P = 0.025), and lactate dehydrogenase activity (82 U/l vs. 232 U/l; P = 0.006 and 123 U/l vs. 303 U/l; P = 0.020). Thirty-day survival was associated with AQP5 –1364A/C genotypes (P = 0.005), with survival of 62% for AA genotypes (58 of 93) but 86% for C-allele carriers (37 of 43). Furthermore, multiple proportional hazard analysis revealed the AA genotype was at high risk for death within 30 days (hazard ratio, 3.53; 95% CI, 1.38 to 9.07; P = 0.009). Conclusions In acute respiratory distress syndrome attributable to bacterial pneumonia, the C-allele of the AQP5 –1364A/C promoter polymorphism is associated with an attenuated pulmonary inflammation and higher 30-day survival. Thus, the AQP5 genotype impacts on inflammation and prognosis in acute respiratory distress syndrome.


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