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

Steffen, Lilian; Ruppert, Clemens; Hoymann, Heinz-Gerd; Funke, Manuela; Ebener, Simone; Kloth, Christina; Mühlfeld, Christian; Ochs, Matthias; Knudsen, Lars; Lopez-Rodriguez, Elena (2017). Surfactant replacement therapy reduces acute lung injury and collapse induration-related lung remodeling in the bleomycin model. American journal of physiology - lung cellular and molecular physiology, 313(2), L313-L327. American Physiological Society 10.1152/ajplung.00033.2017

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

UniBE Contributor:

Funke, Manuela and Ebener, Simone

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1040-0605

Publisher:

American Physiological Society

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

29 Nov 2017 09:44

Last Modified:

18 Jan 2018 15:21

Publisher DOI:

10.1152/ajplung.00033.2017

PubMed ID:

28450283

Uncontrolled Keywords:

bleomycin collapse induration lung injury and fibrosis stereology surfactant

URI:

https://boris.unibe.ch/id/eprint/106741

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