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Physiologic and histopathologic effects of targeted lung denervation in an animal model

Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt...

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Autores principales: Hummel, James P., Mayse, Martin L., Dimmer, Steve, Johnson, Philip J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Physiological Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383645/
https://www.ncbi.nlm.nih.gov/pubmed/30359539
http://dx.doi.org/10.1152/japplphysiol.00565.2018
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author Hummel, James P.
Mayse, Martin L.
Dimmer, Steve
Johnson, Philip J.
author_facet Hummel, James P.
Mayse, Martin L.
Dimmer, Steve
Johnson, Philip J.
author_sort Hummel, James P.
collection PubMed
description Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures. NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects.
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spelling pubmed-63836452019-02-25 Physiologic and histopathologic effects of targeted lung denervation in an animal model Hummel, James P. Mayse, Martin L. Dimmer, Steve Johnson, Philip J. J Appl Physiol (1985) Research Article Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures. NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects. American Physiological Society 2019-01-01 2018-10-25 /pmc/articles/PMC6383645/ /pubmed/30359539 http://dx.doi.org/10.1152/japplphysiol.00565.2018 Text en Copyright © 2019 the American Physiological Society http://creativecommons.org/licenses/by/4.0/deed.en_US Licensed under Creative Commons Attribution CC-BY 4.0: © the American Physiological Society.
spellingShingle Research Article
Hummel, James P.
Mayse, Martin L.
Dimmer, Steve
Johnson, Philip J.
Physiologic and histopathologic effects of targeted lung denervation in an animal model
title Physiologic and histopathologic effects of targeted lung denervation in an animal model
title_full Physiologic and histopathologic effects of targeted lung denervation in an animal model
title_fullStr Physiologic and histopathologic effects of targeted lung denervation in an animal model
title_full_unstemmed Physiologic and histopathologic effects of targeted lung denervation in an animal model
title_short Physiologic and histopathologic effects of targeted lung denervation in an animal model
title_sort physiologic and histopathologic effects of targeted lung denervation in an animal model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383645/
https://www.ncbi.nlm.nih.gov/pubmed/30359539
http://dx.doi.org/10.1152/japplphysiol.00565.2018
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