Reconnecting the vagus nerve to the heart through nerve conduit preserves cardiac function in a minipig model of right cardiac vagotomy
The right vagus nerve is essential for cardiac homeostasis, and its intrathoracic resection can lead to postoperative cardiac complications. Strategies to restore vagal innervation after transection at the cardiac level remain lacking. Here, we show that early reconnection of the right vagus nerve using an implantable chitosan/poly-ε-caprolactone cuff-like nerve guidance conduit preserved cardiac mechanical function in adult male minipigs subjected to right cardiac vagotomy. Treated animals displayed improved global circumferential, longitudinal, and radial strains and reduced diastolic dyssynchrony. Histological analysis revealed partial repair with about 20% viable vagal fascicles, restoration of myocardial parasympathetic fibers, normalization of oxidative stress and aging markers, and prevention of interstitial fibrosis. These findings suggest that maintaining even limited vagal input prevents early cardiac remodeling by mitigating oxidative stress-induced premature senescence of cardiac cells. Reconnection of the right vagus nerve with chitosan/poly-ε-caprolactone cuff-like nerve guidance conduit may represent a therapeutic approach to preventing right vagotomy-induced heart failure after thoracic surgery or cardiothoracic transplantation.
Authors
- V. Lionetti
- Silvia Burchielli (ORCID: https://orcid.org/0000-0002-8237-3921)
- Filippo Agnesi (ORCID: https://orcid.org/0000-0003-1780-8084)
- Lisa Alibrandi
- Alessandro Cellerino (ORCID: https://orcid.org/0000-0003-3834-0097)
- Giovanni Donato Aquaro (ORCID: https://orcid.org/0000-0003-0915-915X)
- Alessandro Carrozzo (ORCID: https://orcid.org/0000-0003-0700-8139)
- Valentina Casieri (ORCID: https://orcid.org/0000-0001-8725-4940)
- A. C. Beltrami
- Ciro Zinno (ORCID: https://orcid.org/0000-0001-8873-8875)
- Letizia Brogi (ORCID: https://orcid.org/0000-0003-3474-9266)
- Anar Dushpanova (ORCID: https://orcid.org/0000-0001-6941-2773)
- Aurora Paganelli (ORCID: https://orcid.org/0009-0007-5112-9786)
- Khatia Gabisonia (ORCID: https://orcid.org/0000-0002-4981-3673)
- Fabio Bernini
- Silvestro Micera (ORCID: https://orcid.org/0000-0003-4396-8217)
- Sabrina Marchetti (ORCID: https://orcid.org/0000-0002-6042-2999)
- Micaela Sgorbini
- Jacopo Carpaneto (ORCID: https://orcid.org/0000-0001-5256-5087)
- Giulia Furini
- Domiziana Terlizzi
- Chrysanthos Grigoratos
- Eugenio Redolfi-Riva
- Valentina Sassu
Institutions
- University of Pisa (IT)
- University of Udine (IT)
- Scuola Normale Superiore (IT)
- Scuola Superiore Sant'Anna (IT)
- Al-Farabi Kazakh National University (KZ)
- Maria Cecilia Hospital (IT)
- Istituto di Fisiologia Clinica (IT)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- San Diego Cardiac Center (US)
- Fondazione Toscana Gabriele Monasterio (IT)
- Regione Toscana
- École Polytechnique Fédérale de Lausanne (CH)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2025-12-24
- DOI
- https://doi.org/10.1126/scitranslmed.aea4306
- Primary Topic
- Vagus Nerve Stimulation Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00