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Airway bypass improves the mechanical properties of explanted emphysematous lungs.

ABSTRACT: By creating artificial communications through bronchial walls into the parenchyma of explanted lungs (airway bypass), we expect to decrease the amount of gas trapped and to increase the rate and volume of air expelled during forced expirations.To describe the mechanism by which airway bypass improves the mechanical properties of the emphysematous lung.Lung compartments and mechanics were measured before and after airway bypass, which was created by placement of three or four stent-supported fenestrations in 10 emphysematous lungs removed at transplantation surgery.Minimal volume after passive deflation decreased by a mean of 1.54 L (range, 0.7-2.5 L) or 60% (range, 37-86%). Explanted VC increased by 1.30 L or 132% (range, 78-318%). Maximal expiratory flows and volumes increased. Flow resistance decreased.Because these data show that airway bypass improves the mechanics of breathing in severely emphysematous lungs in vitro, there is now strong empirical support that this procedure can improve ventilatory function in patients by reducing gas trapping and flow resistance.

SUBMITTER: Choong CK

PROVIDER: S-EPMC2577725 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Airway bypass improves the mechanical properties of explanted emphysematous lungs.

Choong Cliff K CK Macklem Peter T PT Pierce John A JA Das Nitin N Lutey Barbara A BA Martinez Carlo O CO Cooper Joel D JD

American journal of respiratory and critical care medicine 20080731 9

<h4>Rationale</h4>By creating artificial communications through bronchial walls into the parenchyma of explanted lungs (airway bypass), we expect to decrease the amount of gas trapped and to increase the rate and volume of air expelled during forced expirations.<h4>Objectives</h4>To describe the mechanism by which airway bypass improves the mechanical properties of the emphysematous lung.<h4>Methods</h4>Lung compartments and mechanics were measured before and after airway bypass, which was creat ...[more]

PMID: 18669815

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Project description:Pulmonary emphysema is characterized histologically by destruction of alveolar walls and enlargement of air spaces due to lung epithelial cell apoptosis. Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member expressed in lung epithelial cells. CADM1 generates a membrane-associated C-terminal fragment, ?CTF, through A disintegrin- and metalloprotease-10-mediated ectodomain shedding, subsequently releasing the intracellular domain (ICD) through ?-secretase-mediated intramembrane shedding of ?CTF. ?CTF localizes to mitochondria and induces apoptosis in lung epithelial cells. ?CTF contributes to the development and progression of emphysema as a consequence of increased CADM1 ectodomain shedding. The purpose of this study was to examine whether the ICD makes a similar contribution.The ICD was synthesized as a 51-amino acid peptide, and its mutant was synthesized by substituting seven amino acids and deleting two amino acids. These peptides were labeled with fluorescein isothiocyanate and were introduced into various cell lines. ICD peptide-derived fluorescence was well visualized in lung epithelial cells at the site of Mitotracker mitochondrial labeling, but was detected in locations other than mitochondria in other cell types. Mutant peptide-derived fluorescence was detected in locations other than mitochondria, even in lung epithelial cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays revealed that transduction of the ICD peptide increased the proportion of apoptotic cells 2- to 5-fold in the lung epithelial cell lines, whereas the mutant peptide did not. Abundance of the ICD was below the Western blot detection limit in emphysematous (n?=?4) and control (n?=?4) human lungs. However, the ICD was detected only in emphysematous lungs when it was immunoprecipitated with anti-CADM1 antibody (4/4 vs. 0/4, P?=?0.029).As the abundance of ICD molecules was sparse but present, increased CADM1 shedding appeared to contribute to the development of emphysema by generating ?CTF and the ICD in lung epithelial cells.

Dataset Information

Airway bypass improves the mechanical properties of explanted emphysematous lungs.

Publications

Airway bypass improves the mechanical properties of explanted emphysematous lungs.

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