Effect of the sympathetic nervous system in regulating heart rhythm during burst stimulation of the vagus nerve

In cat experiments, the right inferior cardiac nerve was stimulated at a frequency of 2 and 4 Hz and the right vagus by bursts of 1, 2, 4, 8 and 16 impulses. Stimulation of the inferior cardiac nerve shifted the ranges of the heart rate control up the frequency scale. The shift of the range boundaries was mainly determined by the intensity of sympathetic regulation and by the number of impulses in a burst which stimulates the vagus nerve.     

The spectrogram of heart rate in cats following burst stimulation of the vagus nerve

Denervation of the heart (bilateral vagotomy and propranolol) in artificially ventilated cats didn't remove respiratory peaks on the spectrogram of heart rate, while burst stimulation of vagus nerve increased or decreased them several times by synchronization of the heart and vagus rhythms, which in its turn was observed under the bradycardia only. At the same time, the desynchronization of rhythms provoked severe sinus arrhythmia which had a distinct periodic character. Under these conditions, there were high non-respiratory peaks appearing at the spectrogram of the heart rate that indicated existence of two vagus chronotropic effects: a well known tonic one and special intracycle synchronizing effect correcting duration of every cardiac cycle.     

Sensitive control of heart rate in monkeys using burst stimulation of the vagus nerve

Burst vagus stimulation led to synchronization of the cardiac and vagal rhythms at certain frequency ranges. The increase of the number of impulses in a burst from 1 to 16 extended the range of synchronization and shifted it towards lower frequencies forming a total range of exact regulation of the heart rate within 85--40% of the initial rate. It was suggested that vagal effect consists of tonic and synchronizing components.     

迷走神经刺激对记忆的影响

迷走神经刺激(vagus nerve stimulation, VNS)用于终止癫痫发作已经有二十年的历史.期间VNS也用于难治性抑郁的治疗.在治疗过程中研究者发现VNS 对癫痫、抑郁患者的学习和记忆能力有改善作用,这种改善作用在一些动物和人体实验中也得到证实.但VNS在记忆形成的哪个阶段起作用以及如何起作用的具体机制尚不十分清楚.因此,进一步了解VNS对记忆的影响及作用机制有利于探讨记忆形成的生理机制,也为临床治疗特异性记忆障碍和相关神经精神疾病提供新的思路和有益补充.本文综述了近十几年来VNS对记忆的影响及相关机制.     

Could vagus nerve stimulation influence bone remodeling?

Objectives:To investigate the effect of vagus nerve stimulation (VNS) on the bone mineral density (BMD) in epileptic patients.Methods:A prospective cohort study was conducted on individuals with refractory seizures who underwent VNS surgery between January 2012 and December 2018. BMD was measured preoperatively and between 6 months and one year after surgery.Results:Twenty-one patients (mean age (±SD)=23.6±12.3 years) were recruited for the implantation of a VNS device. The mean absolute increase in lumbar BMD in the 21 patients was 0.04±0.04 g/cm² resulting in an overall percent increase from baseline of 4.7±6.1%. BMD increased by an amount ≥ the least significant change (LSC) for the lumbar spine in 13 patients (61.9%). The lumbar Z score also increased in these patients from -1.22±1.15 to -0.88±1.22, P=0.006). Pre and Post VNA femoral BMD was measured in only 11 patients and, of those 3 showed a significant increase in BMD, 1 a significant decrease and 7 no change.Conclusion:The implantation of a VNS was associated with an increase in lumbar BMD. This study could lead to a new application for VNS in the treatment of osteoporosis.     

Transposition of the pacemaker in the right atrium during stimulation of the vagus nerve in the dog

The heart rate and intraatrial latencies between epicardial electrograms from three sites of the right atrium have been studied during vagal stimulation in open-chest dogs. It has been shown that alterations of latencies started at a certain cardiac cycle length irrespective of pacing frequency. A transitional process of changes from a steady latency value in the control to another steady value during vagal stimulation has been observed. The transitional process has been simulated in experimental procedure in which two sites of the right atrium were paced at close and constant frequencies. To interpret the results obtained one-dimensional model of the sinus node has been constructed. According to the model, pacemaker shift within the sinus node results from a competition between two foci of automaticity with close intrinsic frequencies.     

Histopathologic features of the vagus nerve after electrical stimulation in swine

This paper describes the histological features of the vagus nerve after its stimulation with an electrostimulation system that is being developed for morbid obesity treatment. An electrostimulation system was implanted laparoscopically around the ventral vagal trunk of five Large White female pigs (49.63+/-1.94 kg.). Vagal nerve stimulation was performed by continuous constant voltage current pulses. Thoracic samples of both ventral and dorsal vagal trunks were obtained thoracoscopically one month after implantation. Animals were sacrificed one month after thoracoscopic vaguectomy. Tissue samples were then harvested from the vagal nerve at the implantation site, 1cm cranial to it, thoracic portion of ventral and dorsal vagal trunks, sub-diaphragmatic dorsal vagal trunk, left and right vagus nerves. Specimens were analysed with light microscope. The severity of the lesions was graded from 0 to 4 (0: no lesion, 1: mild, 2: moderate, 3: severe and 4: extremely severe), taking into account fibrosis, vascularization, necrosis, fiber degeneration and inflammation. Electrode implantation resulted in thickened epineurium and endoneural connective tissue. The greatest lesion score was evidenced at the leads implantation site in the ventral vagal trunk, followed by, in order of decreasing lesion severity, left vagus nerve, thoracic portion of ventral vagal trunk, subdiaphragmatic dorsal vagal trunk, thoracic portion of dorsal vagal trunk and right vagus nerve. The stimulation device used in this study caused connective tissue growth, greatest in the samples located closer to the implantation site. However, there was no sign of altered vascularization in any studied specimen.     

Hypothalamic evoked potentials to vagus and sciatic nerve stimulation

Hypothalamic evoked potentials to stimulation of the cervical portion of the vagus nerve and the sciatic nerve were recorded in experiments on cats anesthetized with chloralose and immobilized with succinylcholine. When both monopolar and bipolar recording techniques were used the focus of maximal activity of both "visceral" and "somatic" evoked potentials was located in the supramammillary and posterolateral region of the hypothalamus. Responses in the tuberal and anterior hypothalamus occurred in most experiments after a longer latent period, their amplitude was lower, and they were less stable. Evoked potentials in the focus of maximal activity of the posterior hypothalamus are similar in all parameters to responses of the mesencephalic reticular formation. Evoked potentials to stimulation of the visceral nerve have a higher threshold of generation and a lower amplitude than the "somatic" responses and they are inhibited more strongly when the frequency of stimulation is increased. Evoked potentials arising in the hypothalamus in response to stimulation of the vagus and sciatic nerves are regarded as nonspecific responses of reticular type.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 253–260, May–June, 1973.     

Augmentation of respiratory mast cell secretion of histamine caused by vagus nerve stimulation during antigen challenge

We studied the effect of vagus nerve stimulation on the mast cell secretion of histamine after intraarterial (i.a.) administration of Ascaris suum antigen (AA) into the bronchial circulation of 10 randomly selected, natively allergic dogs in vivo. Respiratory mast cell response was measured as the arteriovenous difference (AVd) in histamine concentration across the bronchus. Plasma histamine concentration was determined simultaneously from right atrium, right ventricle, and femoral artery 60 and 15 sec before and 15, 30, 45, 60, 75, and 90 sec after i.a. injection of sham (Kreb-Henseleit) diluent, 1:100, and 1:30 concentrations of AA. The mean AVd in plasma histamine for five parasympathetically blocked animals (neural blockade with hexamethonium and beta-adrenergic blockade with propranolol) was 1.28 +/- 0.61 ng/ml (sham), 5.16 +/- 19.7 ng/ml (1:100 AA), and 36.6 +/- 11.1 ng/ml (1:30 AA). Substantial augmentation was obtained when AA was administered during parasympathetic stimulation in five other animals (beta-adrenergic blockade, no neural blockade), which was caused by continuous bilateral electrical stimulation of the vagus nerves. A mean AVd in plasma histamine of 110 +/- 27.6 ng/ml was obtained after 1:100 AA (p less than 0.001 vs parasympathetic blockade) and 166 +/- 32.4 ng/ml for 1:30 AA (p less than 0.001 vs parasympathetic blockade). Parasympathetic stimulation alone did not cause secretion of histamine. In contrast to the AVd response, parasympathetic stimulation did not augment nonrespiratory mast cell secretion after AA challenge. We conclude that vagus nerve stimulation augments secretion of histamine from respiratory mast cells during antigen challenge. We demonstrate that parasympathetic stimulation may potentiate the response to antigen challenge in central airways through augmented mast cell secretion of mediator.     

Selective recording of electroneurograms from the left vagus nerve of a dog during stimulation of cardiovascular or respiratory systems

Selective electroneurograms (ENGs) from superficial regions of the left vagus nerve of a dog were recorded with a 33-electrode spiral cuff (cuff) implanted on the nerve at the neck in an adult Beagle dog. The electrodes in the cuff were arranged in thirteen groups of three electrodes (GTE 1-13). To identify the relative positions of the particular nerve regions that innervated the heart and lungs, stimulating pulses (2 mA, 200 micros, 20 Hz) were individually delivered to all thirteen GTEs. It was shown that by delivering stimulating pulses to GTEs 4 and 9, heart rate, blood pressure and respiratory rate were modulated. Precisely, only when the stimuli were delivered to GTE 9, the heart rate began to fall and only when the stimuli were delivered to GTE 4 the rate of breathing decreased. To test the selectivity of recording the above-defined groups GTEs 4 and 9 and randomly chosen GTEs 1 and 7 were simultaneously used as recording GTEs while cardio-vascular or respiratory systems were stimulated by carotid artery compression, epinephrine injection and non-invasive, positive end-pressure ventilation. Results showed that stimulations elicited site-specific changes in ENG power spectra recorded from the superficial regions of the vagus nerve. Power spectrum of the ENG recorded with GTE 9, contained frequencies belonging to the neural activity elicited by compression of the carotid artery and injection of epinephrine. The power spectrum of the ENG recorded with GTE 4, contained frequencies belonging to the neural activity elicited by non-invasive, positive end-expiratory pressure ventilation. We concluded that the multi-electrode nerve cuff enables selective stimulation and recording of nerve activity from internal organs.