Sources of Off-Target Effects of Vagus Nerve Stimulation Using the Helical Clinical Lead in Domestic Pigs
| Autor: | James K. Trevathan, Ian W. Baumgart, Erika K. Ross, Evan N. Nicolai, Warren M. Grill, Andrea L. McConico, Andrew J. Shoffstall, Bruce E. Knudsen, Kenneth J. Gustafson, Brian A. Gosink, Nicole A. Pelot, Kip A. Ludwig, Megan L. Settell, Justin C. Williams |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Bradycardia
Cricoarytenoid Muscle medicine.medical_specialty Vagus Nerve Stimulation Swine medicine.medical_treatment 0206 medical engineering Sus scrofa Biomedical Engineering Motor nerve Action Potentials Stimulation 02 engineering and technology LivaNova Article Cellular and Molecular Neuroscience 03 medical and health sciences 0302 clinical medicine Internal medicine medicine bioelectronic medicine electroceuticals Animals 030304 developmental biology 0303 health sciences business.industry Vagus Nerve Anatomy 020601 biomedical engineering Trunk Vagus nerve side effects Cuff neuromodulation Cardiology medicine.symptom Laryngeal Muscles business 030217 neurology & neurosurgery Tinnitus Vagus nerve stimulation |
| Zdroj: | Journal of neural engineering |
| DOI: | 10.1101/2020.01.15.907246 |
| Popis: | Objective Clinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig—an animal model with vagus anatomy similar to human—using the bipolar helical lead deployed clinically. Approach Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses. Main results Contraction of the cricoarytenoid muscle occurred at low amplitudes (∼0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes (∼1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting Aδ-, B-, and C-fibers. Significance Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (μA). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with Aδ- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS. |
| Databáze: | OpenAIRE |
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