Rothman, A. orcid.org/0000-0002-7847-4500, Jonas, M., Castel, D. et al. (6 more authors) (2019) Pulmonary artery denervation using catheter based ultrasonic energy. EuroIntervention, 15 (8). pp. 722-730. ISSN 1774-024X
Abstract
AIMS: Pulmonary arterial hypertension is a devastating disease characterized by pulmonary vascular remodelling and right heart failure. Radio-frequency pulmonary artery denervation (PDN) improves pulmonary hemodynamics in pre-clinical and early clinical studies, however denervation depth is limited. High-frequency non-focused ultrasound can deliver energy to the vessel adventitia, sparing the intima and media. We therefore investigated the feasibility, safety and efficacy of ultrasound PDN.
METHODS AND RESULTS: Histological examination demonstrated that innervation of human pulmonary arteries are predominantly sympathetic (71%), with >40% of nerves at a depth of >4mm. Finite element analysis of ultrasound energy distribution and ex-vivo studies demonstrated generation of temperatures >47ºC to a depth of 10mm. In domestic swine PDN reduced mean pulmonary artery pressure induced by thromboxane A2 in comparison to sham. No adverse events were observed to 95-days. Histological examination identified structural and immunohistological alterations of nerves in PDN treated animals, with sparing of the intima and media and reduced tyrosine hydroxylase staining 95-days post-procedure indicating persistent alteration of the structure of sympathetic nerves.
CONCLUSIONS: Ultrasound PDN is safe and effective in the pre-clinical setting, with energy delivery to a depth that will permit targeting sympathetic nerves in humans.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Europa Digital & Publishing. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number Wellcome Trust (The) 206632/Z/17/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Jul 2019 10:13 |
Last Modified: | 08 Dec 2021 10:47 |
Published Version: | https://eurointervention.pcronline.com/article/pul... |
Status: | Published |
Publisher: | Europa Digital & Publishing |
Refereed: | Yes |
Identification Number: | 10.4244/EIJ-D-18-01082 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:148714 |