In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block

Abstract Background This paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5). Methods Two bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. Results LFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mAp (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP. Conclusion These novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.

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A Reversible Low Frequency Alternating Current Nerve Conduction Block Applied to Mammalian Autonomic Nerves

Sensors ◽

10.3390/s21134521 ◽

2021 ◽

Vol 21 (13) ◽

pp. 4521

Author(s):

M. Ivette Muzquiz ◽

Landan Mintch ◽

M. Ryne Horn ◽

Awadh Alhawwash ◽

Rizwan Bashirullah ◽

...

Keyword(s):

Nervous System ◽

Nerve Block ◽

Nerve Conduction ◽

Conduction Block ◽

Low Frequency ◽

Alternating Current ◽

Autonomic Nerves ◽

Pt Black ◽

Pulse Stimulation ◽

Nerve Conduction Block

Electrical stimulation can be used to modulate activity within the nervous system in one of two modes: (1) Activation, where activity is added to the neural signalling pathways, or (2) Block, where activity in the nerve is reduced or eliminated. In principle, electrical nerve conduction block has many attractive properties compared to pharmaceutical or surgical interventions. These include reversibility, localization, and tunability for nerve caliber and type. However, methods to effect electrical nerve block are relatively new. Some methods can have associated drawbacks, such as the need for large currents, the production of irreversible chemical byproducts, and onset responses. These can lead to irreversible nerve damage or undesirable neural responses. In the present study we describe a novel low frequency alternating current blocking waveform (LFACb) and measure its efficacy to reversibly block the bradycardic effect elicited by vagal stimulation in anaesthetised rat model. The waveform is a sinusoidal, zero mean(charge balanced), current waveform presented at 1 Hz to bipolar electrodes. Standard pulse stimulation was delivered through Pt-Black coated PtIr bipolar hook electrodes to evoke bradycardia. The conditioning LFAC waveform was presented either through a set of CorTec® bipolar cuff electrodes with Amplicoat® coated Pt contacts, or a second set of Pt Black coated PtIr hook electrodes. The conditioning electrodes were placed caudal to the pulse stimulation hook electrodes. Block of bradycardic effect was assessed by quantifying changes in heart rate during the stimulation stages of LFAC alone, LFAC-and-vagal, and vagal alone. The LFAC achieved 86.2±11.1% and 84.3±4.6% block using hook (N = 7) and cuff (N = 5) electrodes, respectively, at current levels less than 110 µAp (current to peak). The potential across the LFAC delivering electrodes were continuously monitored to verify that the blocking effect was immediately reversed upon discontinuing the LFAC. Thus, LFACb produced a high degree of nerve block at current levels comparable to pulse stimulation amplitudes to activate nerves, resulting in a measurable functional change of a biomarker in the mammalian nervous system.

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Long-term effects of hyperpolarization-activated inward current blockade on cardiac parasympathetic activity

EP Europace ◽

10.1093/europace/euab116.541 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

A Scridon ◽

VB Halatiu ◽

AI Balan ◽

DA Cozac ◽

GV Moldovan ◽

...

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

Vagal Stimulation ◽

Sinus Node ◽

Vagal Tone ◽

Right Atrial ◽

The Right

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI Background The autonomic control of the pacemaker current, If, and the molecular mechanisms underlying parasympathetic If modulation are well understood. Conversely, the effects of chronic If blockade on the parasympathetic nervous system and on the heart rate (HR) response to acute parasympathetic changes are still largely unknown. Such interactions could significantly influence the course of patients undergoing chronic therapy with the If blocker ivabradine. Purpose We aimed to assess the effects of long-term If blockade using ivabradine on cardiac autonomic modulation and on the cardiovascular response to acute in vivo and in vitro parasympathetic stimulation. Methods Radiotelemetry ECG transmitters were implanted in 6 Control and 10 ivabradine-treated male Wistar rats (IVA; 3 weeks, 10 mg/kg/day); sympathetic and parasympathetic heart rate variability parameters were assessed. At the end of the study, the right atrium was removed and right atrial HCN(1-4) RNA expression levels were analyzed. The HR and systolic blood pressure (SBP) responses to in vivo electrical stimulation of the right vagus nerve (2–20 Hz) and the spontaneous sinus node discharge rate (SNDR) response to in vitro cholinergic receptors stimulation using carbamylcholine (10-9–10-6 mol/L) were assessed in 6 additional Control and 10 IVA rats. Results At the end of the study, mean 24-h HR was significantly lower in the IVA compared with the Control rats (301.3 ± 7.5 bpm vs. 341.5 ± 8.3 bpm; p< 0.01). Ivabradine administration led to a significant increase in vagal tone and shifted the sympatho-vagal balance towards vagal dominance (awake, asleep, and over 24-h; all p< 0.05). In the Control rats, in vivo vagus nerve stimulation induced a progressive decrease in both the SBP (p = 0.0001) and the HR (p< 0.0001). Meanwhile, in the IVA rats, vagal stimulation had no effect on the HR (p = 0.16) and induced a significantly lower drop in SBP (p< 0.05). Ivabradine-treated rats also presented a significantly lower SNDR drop in response to carbamylcholine (p< 0.01) and significantly higher HCN4 expression (p = 0.02). Conclusion Long-term If blockade using ivabradine caused a significant increase in vagal tone and shifted the autonomic balance towards vagal dominance in rats. Given the highly proarrhythmic effects of vagal activation at the atrial level, these findings could provide an explanation for the increased risk of atrial fibrillation associated with ivabradine use in clinical trials. In addition, ivabradine reduced the HR response to direct muscarinic receptors stimulation, canceled the cardioinhibitory response and blunted the hemodynamic response to in vivo vagal stimulation, and led to significant sinus node HCN4 up-regulation. These data suggest that ivabradine-induced HCN4 and the consequent If up-regulation could render the sinus node less sensitive to acute vagal inputs and could thus protect against excessive bradycardia induced by acute vagal activation.

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Effect of Nerve Cuff Electrode Geometry on Onset Response Firing in High-Frequency Nerve Conduction Block

IEEE Transactions on Neural Systems and Rehabilitation Engineering ◽

10.1109/tnsre.2010.2071882 ◽

2010 ◽

Vol 18 (6) ◽

pp. 658-665 ◽

Cited By ~ 29

Author(s):

D Michael Ackermann ◽

N Bhadra ◽

E L Foldes ◽

X Wang ◽

K L Kilgore

Keyword(s):

Nerve Conduction ◽

High Frequency ◽

Conduction Block ◽

Electrode Geometry ◽

Cuff Electrode ◽

Nerve Cuff ◽

Nerve Cuff Electrode ◽

Onset Response ◽

Nerve Conduction Block

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Nerve Conduction Velocity Selective Recording Using a Multi-contact Cuff Electrode – A Case Study of In-Vitro Vagus Nerve Preparation

IFMBE Proceedings - 15th Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC 2011) ◽

10.1007/978-3-642-21683-1_66 ◽

2011 ◽

pp. 261-263 ◽

Cited By ~ 2

Author(s):

G. A. M. Kurstjens

Keyword(s):

Vagus Nerve ◽

Conduction Velocity ◽

Nerve Conduction ◽

Nerve Conduction Velocity ◽

Cuff Electrode

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Non-NMDA and NMDA receptors transmit area postrema input to aortic baroreceptor neurons in NTS

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.5.h1695 ◽

1998 ◽

Vol 275 (5) ◽

pp. H1695-H1706 ◽

Cited By ~ 14

Author(s):

Chao-Yin Chen ◽

Ann C. Bonham

Keyword(s):

Vagus Nerve ◽

Nmda Receptors ◽

Area Postrema ◽

Low Frequency ◽

Evoked Responses ◽

Neuronal Responses ◽

Afferent Pathways ◽

Aortic Depressor Nerve ◽

Vagal Afferent

We sought to determine whether glutamate acting at both N-methyl-d-aspartate (NMDA) and non-NMDA receptors transmits area postrema (AP) excitatory inputs to nucleus tractus solitarii (NTS) neurons in the aortic baroreceptor or vagal afferent pathways in vivo. In α-chloralose-anesthetized rabbits, we recorded extracellular NTS neuronal responses to low-frequency aortic depressor nerve (ADN), vagus nerve, and AP stimulation and to iontophoresis of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and NMDA during control, iontophoresis of 2,3-dihdroxy-6-nitro-7-sulfamoylbenzo( f)quinoxaline (NBQX),dl-2-amino-5-phosphonovaleric acid (AP5), or both, and recovery conditions. In neurons receiving AP and ADN inputs, NBQX attenuated AP- and ADN-evoked responses by 46 ( P = 0.0206) and 49% ( P = 0.0042). AP5 attenuated AP- and ADN-evoked responses by 39 ( P = 0.0270) and 40% ( P = 0.0157). NBQX + AP5 attenuated AP- and ADN-evoked responses by 74 ( P = 0.0040) and 75% ( P = 0.0028). In neurons receiving AP and vagal inputs, AP transmission was attenuated by 58, 60, and 98%; vagal transmission was attenuated by 62, 35, and 83% during NBQX, AP5, and both antagonists, respectively. These data suggest that both non-NMDA and NMDA receptors transmit AP input to NTS neurons in aortic baroreceptor or vagal afferent pathways.

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NMDA Receptor-Dependent Long-Term Synaptic Depression in the Entorhinal Cortex In Vitro

Journal of Neurophysiology ◽

10.1152/jn.00714.2002 ◽

2003 ◽

Vol 89 (4) ◽

pp. 2112-2119 ◽

Cited By ~ 21

Author(s):

Saı̈d Kourrich ◽

C. Andrew Chapman

Keyword(s):

Nmda Receptor ◽

Receptor Antagonist ◽

Entorhinal Cortex ◽

Low Frequency ◽

Synaptic Depression ◽

Paired Pulse ◽

Pulse Stimulation

The entorhinal cortex receives a large projection from the piriform (primary olfactory) cortex and, in turn, provides the hippocampal formation with most of its cortical sensory input. Synaptic plasticity in this pathway may therefore affect the processing of olfactory information and memory encoding. We have recently found that long-term synaptic depression (LTD) can be induced in this pathway in vivo by repetitive paired-pulse stimulation but not by low-frequency (1 Hz) stimulation with single pulses. Here, we have used field potential recordings to investigate the stimulation parameters and transmitter receptors required for the induction of LTD in the rat entorhinal cortex in vitro. The effectiveness of low-frequency stimulation (900 pulses at 1 or 5 Hz) and repeated delivery of pairs of stimulation pulses (30-ms interpulse interval) was assessed. Only repeated paired-pulse stimulation resulted in lasting LTD, and a low-intensity paired-pulse stimulation protocol that induces LTD in vivo was only effective in the presence of the GABAA receptor antagonist bicuculline (50 μM). LTD could also be induced in normal ACSF, however, by increasing the number of pulse-pairs delivered and by increasing the stimulation intensity during LTD induction. The induction of LTD was blocked by constant bath application of the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovalerate (50 μM), indicating that LTD is dependent on NMDA receptor activation. However, LTD was not blocked by the group I/II mGluR antagonist (RS)-α-ethyl-4-carboxyphenylglycine (500 μM) or by bicuculline (50 μM). The induction of LTD in the entorhinal cortex in vitro is therefore dependent on intense stimulation that recruits activation of NMDA receptors, but does not require concurrent activation of mGluRs or inhibitory synaptic inputs.

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Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation

Journal of Neurophysiology ◽

10.1152/jn.00529.2014 ◽

2015 ◽

Vol 113 (10) ◽

pp. 3923-3929 ◽

Cited By ~ 36

Author(s):

Yogi A. Patel ◽

Robert J. Butera

Keyword(s):

Electrical Stimulation ◽

Sciatic Nerve ◽

Nerve Conduction ◽

Slow Component ◽

Conduction Block ◽

Compound Action Potential ◽

Vagus Nerves ◽

Nerve Recordings ◽

Compound Action

Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5–70 kHz and amplitudes of 0.1–3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function.

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Electrically stimulated contractile activity-induced transcriptomic responses and metabolic remodeling in C2C12 myotubes: twitch vs. tetanic contractions

AJP Cell Physiology ◽

10.1152/ajpcell.00494.2019 ◽

2020 ◽

Vol 319 (6) ◽

pp. C1029-C1044

Author(s):

Yuki Tamura ◽

Karina Kouzaki ◽

Takaya Kotani ◽

Koichi Nakazato

Keyword(s):

Contractile Activity ◽

Low Frequency ◽

C2c12 Myotubes ◽

Respiratory Chain Enzyme ◽

Electrical Pulse Stimulation ◽

Acute Responses ◽

Metabolic Remodeling ◽

Respiratory Chain Enzyme Activity ◽

Pulse Stimulation

The contraction of myotubes using electrical pulse stimulation is a research tool used to mimic muscle contractile activity and exercise in rodents and humans. Most protocols employed in previous work used low-frequency twitch contractions. However, high-frequency tetanus contractions that are more physiologically relevant to muscle contractions in vivo are poorly characterized. In this report, the similarities and differences in acute responses and chronic adaptations with different contractile modes using twitches (2 Hz, continuous, 3 h) and tetanus (66 Hz, on: 5 s/off: 5 s, 3 h) were investigated. RNA sequencing-based transcriptome analysis and subsequent bioinformatics analysis suggest that tetanus may promote bioenergetic remodeling rather than twitch. Based on in silico analyses, metabolic remodeling after three contractile sessions of twitch and tetanus were investigated. Although twitch and tetanus had no significant effect on glycolysis, both types of contraction upregulated glucose oxidation capacity. Both twitch and tetanus qualitatively caused mitochondrial adaptations (increased content, respiratory chain enzyme activity, and respiratory function). The magnitude of adaptation was much greater under tetanus conditions. Our findings indicate that the contraction of myotubes by tetanus may be a useful experimental model, especially in the study of metabolic adaptations in C2C12 myotubes.

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Entrapment Neuropathies: Electrodiagnostic Criteria

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2019.novdec02 ◽

2019 ◽

Vol 24 (6) ◽

pp. 12-15

Author(s):

Jay Blaisdell ◽

James B. Talmage

Keyword(s):

Nerve Conduction ◽

Task Force ◽

Conduction Block ◽

Cubital Tunnel Syndrome ◽

Conduction Delay ◽

Test Results ◽

Sixth Edition ◽

Entrapment Neuropathies ◽

Axon Loss ◽

Tunnel Syndrome

Abstract Like the diagnosis-based impairment (DBI) method and the range-of-motion (ROM) method for rating permanent impairment, the approach for rating compression or entrapment neuropathy in the upper extremity (eg, carpal tunnel syndrome [CTS]) is a separate and distinct methodology in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition. Rating entrapment neuropathies is similar to the DBI method because the evaluator uses three grade modifiers (ie, test findings, functional history, and physical evaluation findings), but the way these modifiers are applied is different from that in the DBI method. Notably, the evaluator must have valid nerve conduction test results and cannot diagnose or rate nerve entrapment or compression without them; postoperative nerve conduction studies are not necessary for impairment rating purposes. The AMA Guides, Sixth Edition, uses criteria that match those established by the Normative Data Task Force and endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM); evaluators should be aware of updated definitions of normal from AANEM. It is possible that some patients may be diagnosed with carpal or cubital tunnel syndrome for treatment but will not qualify for that diagnosis for impairment rating; evaluating physicians must be familiar with electrodiagnostic test results to interpret them and determine if they confirm to the criteria for conduction delay, conduction block, or axon loss; if this is not the case, the evaluator may use the DBI method with the diagnosis of nonspecific pain.

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