Cardiovascular Response to Intraneural Right Vagus Nerve Stimulation in Adult Minipig

Agnesi, Filippo; Zinno, Ciro; Strauss, Ivo; Dushpanova, Anar; Casieri, Valentina; Bernini, Fabio; Terlizzi, Domiziana; Gabisonia, Khatia; Lionetti, Vincenzo; Micera, Silvestro

doi:10.1016/j.neurom.2023.03.002

Cited by 7 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vivo results confirmed previous studies showing that the spatially selective modulation of the VN allows modulating the HR and BP [8], [10] and showed that the here presented hardware could modulate eCAP and physiological parameters. The delivered single-channel stimulation produced a significantly smaller evoked activity when compared to multi-channel stimulation.…”

Section: B Neural Selectivitysupporting

confidence: 89%

Neural stimulation hardware for the selective intrafascicular modulation of the vagus nerve

Strauss

Agnesi

Zinno

et al. 2023

Preprint

View full text Add to dashboard Cite

The neural stimulation of the vagus nerve is able to modulate various functions of the parasympathetic response in different organs. The stimulation of the vagus nerve is a promising approach to treating inflammatory diseases, obesity, diabetes, heart failure, and hypertension. The complexity of the vagus nerve requires highly selective stimulation, allowing the modulation of target-specific organs without side effects. Here, we address this issue by adapting a neural stimulator and developing an intraneural electrode for the particular modulation of the vagus nerve. The neurostimulator parameters such as amplitude, pulse width, and pulse shape were modulated. Single-, and multi-channel stimulation was performed at different amplitudes. For the first time, I polyimide thin-film neural electrode was designed for the specific stimulation of the vagus nerve. In vivo experiments were performed in the adult minipig to validate to elicit electrically evoked action potentials and to modulate physiological functions selectively, validating the selectivity of intraneural stimulation. Electrochemical tests of the electrode and the neurostimulator showed that the stimulation hardware was working correctly. Stimulating the porcine vagus nerve resulted in selective modulation of the vagus nerve. Alpha, beta, and theta waves could be distinguished during single- and multi-channel stimulation. We have shown that the here presented system is able to activate the vagus nerve selectively and can therefore modulate the heart rate, diastolic pressure, and systolic pressure. The here presented system may be used to restore the cardiac loop after denervation by implementing biomimetic stimulation patterns. Presented methods may be used to develop intraneural electrodes adapted for various applications.

show abstract

Section: B Neural Selectivitysupporting

confidence: 89%

Neural stimulation hardware for the selective intrafascicular modulation of the vagus nerve

Strauss

Agnesi

Zinno

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Section: Neural Selectivitysupporting

confidence: 89%

“…This type of fascicular organization suggests that a transversal arrangement of small, intraneural stimulation sites could be ideal for VNS applications. As our group has recently shown, intraneural stimulation suggested that the modulation of the cardiac response in pigs using intraneural electrodes is feasible [10]. The goal of the present study was to further investigate this matter by developing neurostimulation hardware specifically tailored for the stimulation of the cardiac fascicles of the VN.…”

Section: Introductionmentioning

confidence: 96%

Neural Stimulation Hardware for the Selective Intrafascicular Modulation of the Vagus Nerve

Strauss,

Agnesi,

Zinno

et al. 2023

IEEE Trans. Neural Syst. Rehabil. Eng.

Self Cite

View full text Add to dashboard Cite

The neural stimulation of the vagus nerve is able to modulate various functions of the parasympathetic response in different organs. The stimulation of the vagus nerve is a promising approach to treating inflammatory diseases, obesity, diabetes, heart failure, and hypertension. The complexity of the vagus nerve requires highly selective stimulation, allowing the modulation of target-specific organs without side effects. Here, we address this issue by adapting a neural stimulator and developing an intraneural electrode for the particular modulation of the vagus nerve. The neurostimulator parameters such as amplitude, pulse width, and pulse shape were modulated. Single-, and multichannel stimulation was performed at different amplitudes. For the first time, a polyimide thin-film neural electrode was designed for the specific stimulation of the vagus nerve. In vivo experiments were performed in the adult minipig to validate to elicit electrically evoked action potentials and to modulate physiological functions, validating the spatial selectivity of intraneural stimulation. Electrochemical tests of the electrode and the neurostimulator showed that the stimulation hardware was working correctly. Stimulating the porcine vagus nerve resulted in spatially selective modulation of the vagus nerve. ECAP belonging to alpha and beta fibers could be distinguished during single-and multi-channel stimulation. We have shown that the here presented system is able to activate the vagus nerve and can therefore modulate the heart rate, diastolic pressure, and systolic pressure. The here presented system may be used to restore the cardiac loop after denervation by implementing biomimetic stimulation patterns. Presented methods may be used to develop intraneural electrodes adapted for various applications.

show abstract

“…By selectively stimulating the cardiac efferents and avoiding majority of the afferent fibers of the vagus nerve, titration could be avoided. As shown in Hadaya et al (2023) 3 , considerable cardioprotection was achieved when VNS was applied at the neural fulcrum. However, titration subsequent to MI was required to reach this optimal point.…”

Section: Discussionmentioning

confidence: 83%

“…More recently, sVNS of the vagus nerve was also reported in the pig vagus nerve using the same 14-electrode double-ring array 20 , an 8-electrode single-ring array 21 and a 6-electrode FDA investigational device 22 . Selective stimulation of the right vagus nerve with multiple contacts was also achieved recently for modulation of heart rate 23 ; however, this work employed an invasive Transversal Intrafascicular Multichannel Electrode (TIME) array. Recently, the organization of the cervical vagus nerve in swine was investigated by Thompson et al (2023) 20 , who showed a degree of cross-sectional organization for branches innervating the larynx, heart and lungs, which cross-correlated between sVNS, micro-computed tomography (microCT) and electrical impedance tomography (EIT).…”

Section: Introductionmentioning

confidence: 99%

Anatomical and functional organization of cardiac fibers in the porcine cervical vagus nerve allows spatially selective efferent neuromodulation

Thompson,

Ravagli,

Mastitskaya

et al. 2024

Preprint

View full text Add to dashboard Cite

Background and Objectives: Spatially-selective vagus nerve stimulation (sVNS) offers a promising solution to mitigate the off-target effects associated with traditional VNS, potentially serving as a precise method for addressing chronic heart failure (HF) by specifically targeting efferent cardiac fibers. This approach holds the potential to enhance therapeutic outcomes by avoiding off-target effects and eliminating the current need for time-consuming titration required for optimal VNS. Recent studies have demonstrated the independent modulation of breathing rate, heart rate, and laryngeal contraction through sVNS. However, the spatial organization of afferent and efferent cardiac-related fibers within the vagus nerve remains unexplored. Methods and Results: By using trial-and-error sVNS in vivo in combination with ex vivo micro-computed tomography fascicle tracing, we show the significant spatial separation of cardiac afferent and efferent fibers (179±55° SD microCT, p<0.05 and 200±137° SD, p<0.05 sVNS - degrees of separation across a cross-section of nerve) at the mid-cervical level. Cardiac afferent fibers are located in proximity to pulmonary fibers consistent with recent findings of cardiopulmonary convergent neurons and circuits. We demonstrate the ability to selectively elicit therapeutic-related effect (heart rate decrease) without stimulating afferent-related reflexes. Conclusions: By investigating the spatial organization of cardiac-related fibers within the vagus nerve, our findings pave the way for more targeted neuromodulation, thereby reducing off-target effects and eliminating the need for titration. This, in turn, will enhance the precision and efficacy of VNS therapy in treating HF, myocardial infarction and other conditions, allowing for therapeutic effect to be achieved much sooner.

show abstract

Cardiovascular Response to Intraneural Right Vagus Nerve Stimulation in Adult Minipig

Cited by 7 publications

References 35 publications

Neural stimulation hardware for the selective intrafascicular modulation of the vagus nerve

Neural stimulation hardware for the selective intrafascicular modulation of the vagus nerve

Neural Stimulation Hardware for the Selective Intrafascicular Modulation of the Vagus Nerve

Anatomical and functional organization of cardiac fibers in the porcine cervical vagus nerve allows spatially selective efferent neuromodulation

Contact Info

Product

Resources

About