scholarly journals Surfactant replacement therapy reduces acute lung injury and collapse induration-related lung remodeling in the bleomycin model

2017 ◽  
Vol 313 (2) ◽  
pp. L313-L327 ◽  
Author(s):  
Lilian Steffen ◽  
Clemens Ruppert ◽  
Heinz-Gerd Hoymann ◽  
Manuela Funke ◽  
Simone Ebener ◽  
...  
Keyword(s):  
Surface Tension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Replacement Therapy ◽  
Wall Thickness ◽  
Inflammatory Markers ◽  
Septal Wall ◽  
Surfactant Replacement Therapy ◽  
Septal Wall Thickness ◽  
Surfactant Dysfunction

Bleomycin-induced lung injury leads to surfactant dysfunction and permanent loss of alveoli due to a remodeling process called collapse induration. Collapse induration also occurs in acute interstitial lung disease and idiopathic pulmonary fibrosis in humans. We hypothesized that surfactant dysfunction aggravates lung injury and early remodeling resulting in collapse induration within 7 days after lung injury. Rats received bleomycin to induce lung injury and either repetitive surfactant replacement therapy (SRT: 100 mg Curosurf/kg BW = surf group) or saline (0.9% NaCl = saline group). After 3 (D3) or 7 (D7) days, invasive pulmonary function tests were performed to determine tissue elastance (H) and static compliance (Cst). Bronchoalveolar lavage (BAL) was taken for surfactant function, inflammatory markers, and protein measurements. Lungs were fixed by vascular perfusion for design-based stereology and electron microscopic analyses. SRT significantly improved minimum surface tension of alveolar surfactant as well as H and Cst at D3 and D7. At D3 decreased inflammatory markers including neutrophilic granulocytes, IL-1β, and IL-6 correlated with reduced BAL-protein levels after SRT. Numbers of open alveoli were significantly increased at D3 and D7 in SRT groups whereas at D7 there was also a significant reduction in septal wall thickness and parenchymal tissue volume. Septal wall thickness and numbers of open alveoli highly correlated with improved lung mechanics after SRT. In conclusion, reduction in surface tension was effective to stabilize alveoli linked with an attenuation of parameters of acute lung injury at D3 and collapse induration at D7. Hence, SRT modifies disease progression to collapse induration.

scholarly journals Resolvin D1 and Lipoxin A4 Improve Alveolarization and Normalize Septal Wall Thickness in a Neonatal Murine Model of Hyperoxia-Induced Lung Injury

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98773 ◽  
Author(s):  
Camilia R. Martin ◽  
Munir M. Zaman ◽  
Calvin Gilkey ◽  
Maria V. Salguero ◽  
Hatice Hasturk ◽  
...  
Keyword(s):  
Lung Injury ◽  
Wall Thickness ◽  
Murine Model ◽  
Resolvin D1 ◽  
Lipoxin A4 ◽  
Septal Wall ◽  
Septal Wall Thickness

Decreased Surfactant Protein-B Expression and Surfactant Dysfunction in a Murine Model of Acute Lung Injury

2001 ◽  
Vol 25 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Edward P. Ingenito ◽  
Rene Mora ◽  
Michael Cullivan ◽  
Yolanda Marzan ◽  
Kathleen Haley ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Murine Model ◽  
Surfactant Protein ◽  
Surfactant Protein B ◽  
Surfactant Dysfunction ◽  
Protein B

scholarly journals The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

2015 ◽  
Vol 309 (9) ◽  
pp. L959-L969 ◽  
Author(s):  
Lars Knudsen ◽  
Elena N. Atochina-Vasserman ◽  
Christopher B. Massa ◽  
Bastian Birkelbach ◽  
Chang-Jiang Guo ◽  
...  
Keyword(s):  
Surface Area ◽  
Wall Thickness ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
Lung Mechanics ◽  
Surfactant Protein D ◽  
Wall Thickening ◽  
Interstitial Tissue ◽  
Septal Wall ◽  
Septal Wall Thickness

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces.

scholarly journals Investigating biases in the measurement of apparent alveolar septal wall thickness with hyperpolarized 129Xe MRI

2020 ◽  
Vol 84 (6) ◽  
pp. 3027-3039
Author(s):  
Kai Ruppert ◽  
Faraz Amzajerdian ◽  
Yi Xin ◽  
Hooman Hamedani ◽  
Luis Loza ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Septal Wall ◽  
Hyperpolarized 129Xe ◽  
Septal Wall Thickness

scholarly journals Effect of bovine lactoferrin as a novel therapeutic agent in a rat model of sepsis-induced acute lung injury

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nannan Han ◽  
Hengjie Li ◽  
Gang Li ◽  
Ye Shen ◽  
Min Fei ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Count ◽  
Rat Model ◽  
Inflammatory Markers ◽  
Therapeutic Agent ◽  
Total Cell ◽  
Bovine Lactoferrin ◽  
Total Cell Count

Abstract Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.

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