共查询到20条相似文献,搜索用时 15 毫秒
1.
The effect of spinal cord stimulation (SCS) on heart rate (HR) was studied in 25 patients without cardiological symptoms, who were undergoing SCS for various reasons. HR at rest significantly decreased during SCS. Physiological and pharmacological maneuvers of sympathetic and parasympathetic activation or blockade before and during SCS indicate that SCS interferes with the central mechanisms of regulation of HR mainly by inducing a functional sympathectomy, and that such an effect is mediated by an action on spinal cord ascending fibers. 相似文献
2.
Iu P Gerasimenko V D Avelev O A Nikitin I A Lavrov 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2001,87(9):1161-1170
An area initiating locomotor activity under conditions of the spinal cord surface stimulation (SCS) was found at the upper border of the lumbar enlargement (L4-5 spinal segments). Parameters of the SCS for activation of the spinal stepping generator (SSG) were identified. Activation of the SSG under the SCS was shown to occur because of interaction of the spinal and peripheral mechanisms. Primary role in the SSG initiation during the SCS belongs to the propriospinal system of the dorsolateral funiculi. 相似文献
3.
Pattern of expiratory muscle activation during lower thoracic spinal cord stimulation. 总被引:1,自引:0,他引:1
A F DiMarco J R Romaniuk K E Kowalski G Supinski 《Journal of applied physiology》1999,86(6):1881-1889
Large positive airway pressures (Paws) can be generated by lower thoracic spinal cord stimulation (SCS), which may be a useful method of restoring cough in spinal cord-injured patients. Optimal electrode placement, however, requires an assessment of the pattern of current spread during SCS. Studies were performed in anesthetized dogs to assess the pattern of expiratory muscle recruitment during SCS applied at different spinal cord levels. A multicontact stimulating electrode was positioned over the surface of the lower thoracic and upper lumbar spinal cord. Recording electromyographic electrodes were placed at several locations in the abdominal and internal intercostal muscles. SCS was applied at each lead, in separate trials, with single shocks of 0.2-ms duration. The intensity of stimulation was adjusted to determine the threshold for development of the compound action potential at each electrode lead. The values of current threshold for activation of each muscle formed parabolas with minimum values at specific spinal root levels. The slopes of the parabolas were relatively steep, indicating that the threshold for muscle activation increases rapidly at more cephalad and caudal sites. These results were compared with the effectiveness of SCS (50 Hz; train duration, 1-2 s) at different spinal cord levels to produce changes in Paw. Stimulation at the T9 and T10 spinal cord level resulted in the largest positive Paws with a single lead. At these sites, threshold values for activation of the internal intercostal (7-11th interspaces) upper portions of external oblique, rectus abdominis, and transversus abdominis were near their minimum. Threshold values for activation of the caudal portions of the abdominal muscles were high (>50 mA). Our results indicate that 1) activation of the more cephalad portions of the abdominal muscles is more important than activation of caudal regions in the generation of positive Paws and 2) it is not possible to achieve complete activation of the expiratory muscles with a single electrode lead by using modest current levels. In support of this latter conclusion, a two-electrode lead system results in more uniform expiratory muscle activation and significantly greater changes in Paw. 相似文献
4.
Ding X Ardell JL Hua F McAuley RJ Sutherly K Daniel JJ Williams CA 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,294(1):R93-101
The upper cervical spinal region functions as an intraspinal controller of thoracic spinal reflexes and contributes to neuronal regulation of the ischemic myocardium. Our objective was to determine whether stimulation of the C2 cervical spinal cord (SCS) of rats modified the input signal at the thoracic spinal cord when cardiac ischemia-sensitive (sympathetic) afferents were activated by transient occlusion of the left anterior descending coronary artery (CoAO). Changes in c-Fos expression were used as an index of neuronal activation within the spinal cord and brain stem. The pattern of substance P (SP) release, a putative nociceptive transmitter, was measured using antibody-coated microprobes. Two SCS protocols were used: reactive SCS, applied concurrently with intermittent CoAO and preemptive, sustained SCS starting 15 min before and continuing during the repeated intermittent CoAO. CoAO increased SP release from laminae I and II in the T4 spinal cord above resting levels. Intermittent SCS with CoAO resulted in greater levels of SP release from deeper laminae IV-VII in T4 than CoAO alone. In contrast, SP release from laminae I and II was inhibited when CoAO was applied during preemptive, sustained SCS. Preemptive SCS likewise reduced c-Fos expression in the T4 spinal cord (laminae I-V) and nucleus tractus solitarius but increased expression in the intermediolateral cell column of T4 compared with CoAO alone. These results suggest that preemptive SCS from the high cervical region modulates sensory afferent signaling from the ischemic myocardium. 相似文献
5.
A F DiMarco K E Kowalski G Supinski J R Romaniuk 《Journal of applied physiology》2002,92(6):2341-2346
Lower thoracic spinal cord stimulation (SCS) may be a useful method to restore an effective cough mechanism. In dogs, two groups of studies were performed to evaluate the mechanism of the expiratory muscle activation during stimulation at the T(9)-T(10) level, which results in the greatest changes in airway pressure. In one group, expiratory muscle activation was monitored by evoked muscle compound action potentials (CAPs) from the internal intercostal muscles in the 10th, 11th, and 12th interspaces and from portions of the external oblique innervated by the L(1) and L(2) motor roots. SCS, applied with single shocks, resulted in short-latency CAPs at T(10) but not at more caudal levels. SCS resulted in long-latency CAPs at each of the more caudal caudal recording sites. Bilateral dorsal column sectioning, just below the T(11) spinal cord level, did not affect the short-latency CAPs but abolished the long-latency CAPs and also resulted in a fall in airway pressure generation. In the second group, sequential spinal root sectioning was performed to assess their individual mechanical contribution to pressure generation. Section of the ventral roots from T(8) through T(10) resulted in negligible changes, whereas section of more caudal roots resulted in a progressive reduction in pressure generation. We conclude that 1) SCS at the T(9)-T(10) level results in direct activation of spinal cord roots within two to three segments of the stimulating electrode and activation of more distal roots via spinal cord pathways, and 2) pathway activation of motor roots makes a substantial contribution to pressure generation. 相似文献
6.
Ding X Hua F Sutherly K Ardell JL Williams CA 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(5):R1519-R1528
During myocardial ischemia, the cranial cervical spinal cord (C1-C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I-V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the kappa-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart. 相似文献
7.
Mechanical contribution of expiratory muscles to pressure generation during spinal cord stimulation.
A F DiMarco J R Romaniuk K E Kowalski G Supinski 《Journal of applied physiology》1999,87(4):1433-1439
Lower thoracic spinal cord stimulation (SCS) results in the generation of large positive airway pressures (Paw) and may be a useful method of restoring cough in patients with spinal cord injury. The purpose of the present study was to assess the mechanical contribution of individual respiratory muscles to pressure generation during SCS. In anesthetized dogs, SCS was applied at different spinal cord levels by using a 15-lead multicontact electrode before and after sequential ablation of the external and internal obliques, transversus abdominis (TA), rectus abdominis, and internal intercostal muscles. Paw was monitored after tracheal occlusion. SCS at the T(9) spinal cord level resulted in maximal changes in Paw (60 +/- 3 cmH(2)O). Section of the oblique muscles resulted in a fall in Paw to 29 +/- 2 cmH(2)O. After subsequent section of the rectus abdominis and TA, Paw fell to 25 +/- 2 and 12 +/- 1 cmH(2)O respectively. There was a small remaining Paw (4 +/- 1 cmH(2)O) after section of the internal intercostal nerves. Stimulation with a two-electrode lead system (T(9) + T(13)) resulted in significantly greater pressure generation compared with a single-electrode lead due to increased contributions from the obliques and transversus muscles. In a separate group of animals, Paw generation was monitored after section of the abdominal muscles and again after section of the external intercostal and levator costae muscles. These studies demonstrated that inspiratory intercostal muscle stimulation resulted in only a small opposing inspiratory action (=3 cmH(2)O). We conclude that, during SCS, 1) contraction of the obliques and TA muscles makes the largest contribution to changes in Paw, and 2) stimulation with a two-electrode lead system results in more complete abdominal muscle activation and enhanced mechanical actions of the obliques and transversus muscles. 相似文献
8.
Inspiratory action of separate external and parasternal intercostal muscle contraction 总被引:1,自引:0,他引:1
We have previously shown that electrical stimulation of the thoracic spinal cord produces near maximal activation of the inspiratory intercostal muscles. In the present investigation, we used this technique to evaluate the relative capacity of separate external (EI) and parasternal intercostal (PA) muscle contraction to produce changes in airway pressure and inspired volume. Studies were performed in 23 anesthetized phrenicotomized dogs. Electrical stimuli were applied to the spinal cord after hyperventilation-induced apnea, before and after sequentially severing either the PA or EI muscles from the first through sixth intercostal spaces. During spinal cord stimulation (SCS), measurements were made of inspired volume (delta V) with the airway open and negative airway pressure (delta P) during tracheal occlusion. Compared with control values, sectioning of the PA muscles resulted in a 40.9% reduction in delta P and 35.7% reduction in delta V during SCS. In other animals, initial sectioning of the EI muscles produced reductions in delta P and delta V of 67.4 and 63.0, respectively, during SCS. After subsequent section of the PA muscles, SCS produced only negligible inspired volumes and changes in airway pressure. We conclude that 1) the EI and PA muscles are each capable of generating substantial changes in airway pressure and large inspired volumes and 2) the ventilatory capacity of the EI muscles exceeds that of the PA muscles. 相似文献
9.
目的:本研究旨在探讨阿米替林干预对脊髓电刺激(SCS)治疗幻肢痛疗效的影响。方法:研究对象为2007年1月至2009年6月在我科行SCS置入术且符合入组标准并自愿参加研究的幻肢痛患者,共获7例。术后SCS均开启,阿米替林治疗在术后1个月时开始。疼痛、情绪、生活质量评估采用视觉模拟评分法(visual analogue scales,VAS法),现时疼痛强度评分法(presentpain intensity。PPI),综合性医院焦虑抑郁量表(The Hospital Anxiety and Depression Scale,HAD),疼痛失能指数(Pain disability index,PDI)。结果:(1)开启SCS后患者的疼痛、抑郁焦虑情绪及生活质量均得到显著改善。(2)所有患者在使用阿米替林治疗以后疼痛、情绪及生活质量也显著改善。结论:阿米替林能显著提高SCS对幻肢痛的疗效。 相似文献
10.
Opioid peptide response to spinal cord stimulation in chronic critical limb ischemia 总被引:1,自引:0,他引:1
Fontana F Bernardi P Lanfranchi G Spampinato S Di Toro R Conti E Bonafè F Coccheri S 《Peptides》2004,25(4):571-575
Twelve patients with chronic critical limb ischemia in whom a spinal cord stimulation (SCS) system had been implanted for at least one year had increased microvascular flow and achieved healing of trophic acral lesions. After switching off the system, the clinical improvement persisted for 10 days and the neurohormonal pattern showed high plasma values of beta-endorphin and Met-enkephalin, normal dynorphin B, endothelin-1 and catecholamines, and low nitric oxide. Met-enkephalin levels were further increased (P < 0.01) immediately after switching on the electrical stimulation again. The persistence of high plasma opioid levels after switching off the spinal cord stimulation explains the absence of subjective complaints and suggests an involvement of opioids in the regulation and improvement of the microcirculation. 相似文献
11.
Joost L. M. Jongen Helwin Smits Tiziana Pederzani Malik Bechakra Mehdi Hossaini Sebastiaan K. Koekkoek Frank J. P. M. Huygen Chris I. De Zeeuw Jan C. Holstege Elbert A. J. Joosten 《PloS one》2014,9(10)
Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level. 相似文献
12.
We recorded the spike activity from spinal neurons In rats with a model of neuropathy after ligation of then. ishiadicus. A significantly increased frequency of background discharges and responsiveness to nonnoxious stimuli were observed in dorsal
horn wide-dynamic range (convergent) neurons in a group of allodynic rats, as compared with non-allodynic and intact rats.
Spinal cord stimulation (SCS) Induced a significant depression of both the principal responses and afterdischarges in allodynic
rats. The frequency of background discharges was markedly decreased in approximately one third of the neurons. These effects
outlasted SCS by about 10 rain. The moderating effect of SCS is considered a result of activation of distinctly different
and complementary mechanisms: segmental and transsupraspinal. The former appears to be the most important in allodynic animals. 相似文献
13.
Janssen SP Gerard S Raijmakers ME Truin M Van Kleef M Joosten EA 《Neurochemistry international》2012,60(1):21-30
Elevated spinal extracellular γ-aminobutyric acid (GABA) levels have been described during spinal cord stimulation (SCS)-induced analgesia in experimental chronic peripheral neuropathy. Interestingly, these increased GABA levels strongly exceeded the time frame of SCS-induced analgesia. In line with the former, pharmacologically-enhanced extracellular GABA levels by GABAB receptor agonists in combination with SCS in non-responders to SCS solely could convert these non-responders into responders. However, similar treatment with GABAA receptor agonists and SCS is known to be less efficient. Since K+ Cl− cotransporter 2 (KCC2) functionality strongly determines proper GABAA receptor-mediated inhibition, both decreased numbers of GABAA receptors as well as reduced KCC2 protein expression might play a pivotal role in this loss of GABAA receptor-mediated inhibition in non-responders. Here, we explored the mechanisms underlying both changes in extracellular GABA levels and impaired GABAA receptor-mediated inhibition after 30 min of SCS in rats suffering from partial sciatic nerve ligation (PSNL). Immediately after cessation of SCS, a decreased spinal intracellular dorsal horn GABA-immunoreactivity was observed in responders when compared to non-responders or sham SCS rats. One hour later however, GABA-immunoreactivity was already increased to similar levels as those observed in non-responder or sham SCS rats. These changes did not coincide with alterations in the number of GABA-immunoreactive cells. C-Fos/GABA double-fluorescence clearly confirmed a SCS-induced activation of GABA-immunoreactive cells in responders immediately after SCS. Differences in spinal dorsal horn GABAA receptor-immunoreactivity and KCC2 protein levels were absent between all SCS groups. However, KCC2 protein levels were significantly decreased compared to sham PSNL animals. In conclusion, reduced intracellular GABA levels are only present during the time frame of SCS in responders and strongly point to a SCS-mediated on/off GABAergic release mechanism. Furthermore, a KCC2-dependent impaired GABAA receptor-mediated inhibition seems to be present both in responders and non-responders to SCS due to similar KCC2 and GABAA receptor levels. 相似文献
14.
Southerland EM Milhorn DM Foreman RD Linderoth B DeJongste MJ Armour JA Subramanian V Singh M Singh K Ardell JL 《American journal of physiology. Heart and circulatory physiology》2007,292(1):H311-H317
Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of left anterior descending coronary arterial occlusion (CAO) followed by 3 h of reperfusion (control), were compared with those with preemptive SCS (starting 15 min before and continuing throughout the 30-min CAO) or reactive SCS (started at 1 or 28 min of CAO). For SCS, the dorsal C8-T2 segments of the spinal cord were stimulated electrically (50 Hz, 0.2 ms, 90% of motor threshold). For preemptive SCS, separate groups of animals were pretreated 15 min before SCS onset with 1) vehicle, 2) prazosin (alpha(1)-adrenoceptor blockade), or 3) timolol (beta-adrenoceptor blockade). Infarct size (IS), measured with tetrazolium, was expressed as a percentage of risk zone. In controls exposed to 30 min of CAO, IS was 36.4 +/- 9.5% (SD). Preemptive SCS reduced IS to 21.8 +/- 6.8% (P < 0.001). Preemptive SCS-mediated infarct reduction was eliminated by prazosin (36.6 +/- 8.8%) and blunted by timolol (29.4 +/- 7.5%). Reactive SCS did not reduce IS. SCS increased phosphorylation of cardiac PKC. SCS did not alter blood pressure or heart rate. We conclude that preemptive SCS reduces the size of infarcts induced by transient CAO; such cardioprotection involves cardiac adrenergic neurons. 相似文献
15.
16.
Holger Diedrichs Carsten Zobel Peter Theissen Michael Weber Athanassios Koulousakis Harald Schicha Robert HG Schwinger 《Trials》2005,6(1):1-7
Background
Spinal cord electrical stimulation (SCS) has shown to be a treatment option for patients suffering from angina pectoris CCS III-IV although being on optimal medication and not suitable for conventional treatment strategies, e.g. CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under SCS therapy, there are only a few short-term studies that investigated alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct effect on myocardial perfusion.Methods
A prospective study to investigate the short- and long-term effect of spinal cord stimulation (SCS) on myocardial ischemia in patients with refractory angina pectoris and coronary multivessel disease was designed. Myocardial ischemia was measured by MIBI-SPECT scintigraphy 3 months and 12 months after the beginning of neurostimulation. To further examine the relation between cardiac perfusion and functional status of the patients we measured exercise capacity (bicycle ergometry and 6-minute walk test), symptoms and quality of life (Seattle Angina Questionnaire [SAQ]), as well.Results
31 patients (65 ± 11 SEM years; 25 male, 6 female) were included into the study. The average consumption of short acting nitrates (SAN) decreased rapidly from 12 ± 1.6 times to 3 ± 1 times per week. The walking distance and the maximum workload increased from 143 ± 22 to 225 ± 24 meters and 68 ± 7 to 96 ± 12 watt after 3 months. Quality of life increased (SAQ) significantly after 3 month compared to baseline, as well. No further improvement was observed after one year of treament. Despite the symptomatic relief and the improvement in maximal workload computer based analysis (Emory Cardiac Toolbox) of the MIBI-SPECT studies after 3 months of treatment did not show significant alterations of myocardial ischemia compared to baseline (16 patients idem, 7 with increase and 6 with decrease of ischemia, 2 patients dropped out during initial test phase). Interestingly, in the long-term follow up after one year 16 patients (of 27 who completed the one year follow up) showed a clear decrease of myocardial ischemia and only one patient still had an increase of ischemia compared to baseline.Conclusion
Thus, spinal cord stimulation not only relieves symptoms, but reduces myocardial ischemia as well. However, since improvement in symptoms and exercise capacity starts much earlier, decreased myocardial ischemia might not be a direct effect of neurostimulation but rather be due to a better coronary collateralisation because of an enhanced physical activity of the patients. 相似文献17.
常崇旺耿宁李楠王景马久红王学廉 《现代生物医学进展》2011,11(21):4061-4064
目的:本研究旨在探讨阿米替林干预对脊髓电刺激(SCS)治疗幻肢痛疗效的影响。方法:研究对象为2007年1月至2009年6月在我科行SCS置入术且符合入组标准并自愿参加研究的幻肢痛患者,共获7例。术后SCS均开启,阿米替林治疗在术后1个月时开始。疼痛、情绪、生活质量评估采用视觉模拟评分法(visualanaloguescales,VAS法),现时疼痛强度评分法(presentpainin-tensity,PPI),综合性医院焦虑抑郁量表(The Hospital Anxiety and Depression Scale,HAD),疼痛失能指数(Pain disability index,PDI)。结果:(1)开启SCS后患者的疼痛、抑郁焦虑情绪及生活质量均得到显著改善。(2)所有患者在使用阿米替林治疗以后疼痛、情绪及生活质量也显著改善。结论:阿米替林能显著提高SCS对幻肢痛的疗效。 相似文献
18.
Investigation on cerebrospinal fluid opioids and neurotransmitters related to spinal cord stimulation 总被引:1,自引:0,他引:1
L Tonelli T Setti A Falasca E Martignoni E Torcia F M Calcaterra G A Merli F Facchinetti 《Applied neurophysiology》1988,51(6):324-332
The purpose of this study was to assess the biochemical mechanisms underlying spinal cord stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation. Basal cerebrospinal fluid beta-endorphin levels were below the normal range. No significant change of norepinephrine, epinephrine, dopamine, beta-endorphin, beta-lipotropin, or adrenocorticotropic hormone levels were found after SCS. A 50% increase of cerebrospinal beta-endorphin and beta-lipotropin levels occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the derangement of the endogenous opioid system in chronic pain conditions and suggest that the beta-endorphin response to SCS could have clinical value in predicting the success of treatment. 相似文献
19.
J Kiwerski 《Polski tygodnik lekarski (Warsaw, Poland : 1960)》1990,45(4-5):77-81
A group of 1000 patients treated for traumatic injuries to the spinal cord in cervical segment was analysed. These patients were hospitalized at the Department of Rehabilitation in Konstancin in 1967-1987. The most frequent causes of spine injuries, level and degree of lesions to the spinal cord, techniques of conservative treatment and surgeries and results of therapy are discussed. Significant neurological improvement was observed in 62% of the treated patients. An improvement depended on the degree of lesion to the spinal cord, time and method of therapy, mechanism of trauma, and to some extent patients' age. Finally, hospitalization duration was analysed which greatly depend on the degree of lesions to the spinal cord. 相似文献
20.
Gibbons DD Southerland EM Hoover DB Beaumont E Armour JA Ardell JL 《American journal of physiology. Regulatory, integrative and comparative physiology》2012,302(3):R357-R364
Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ~4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential. 相似文献