肺叶切除术后自主神经在房颤中的作用

目的探讨自主神经在肺叶切除术后房颤发生中的作用。方法对281例60岁以上接受肺叶或全肺切除术的患者进行术后连续96h的动态心电图监测,对出现房颤患者在房颤发生前2h的心率变异性指标进行分析,并与同期性别、年龄相匹配未发生房颤患者相应时间段的心率变异性指标进行对比研究,分析交感神经张力与迷走神经张力在房颤发生前的变化。结果 281例肺切除患者术后有48例患者出现房颤,发生率17.1%;房颤组及对照组的病例基本资料无明显统计学差异,房颤组在房颤发生前2h反映迷走神经张力的指标SDNN、rMSSD、pNN50、HF明显增高,而反映交感/副交感神经平衡的指标LF/HF与对照组降低无统计学差异;而在房颤发生前5min SDNN、rMSSD、pNN50、HF明显增高,而LF/HF比值明显降低,表明迷走神经张力明显增高。结论肺叶切除术后的房颤发生前心率变异性存在明显增高的表现,肺叶切除术后交感神经张力明显增高的背景下迷走神经张力竞争性增高可能是导致房颤发生的重要机制。     

心脏淀粉样变患者心率变异性分析

目的 研究心脏淀粉样变(cardiac amyloidosis,CA)患者心率变异性变化规律及其临床意义.方法 选择30例CA住院患者(CA组)与33例健康成人志愿者(对照组)进行24 h动态心电图心率变异性指标比较、分析.结果 与对照组比较,CA组的心率变异性指标SDNN、SDNN Index、三角指数、SDANN、rMSSD、pNN50、高频功率(HF)、低频功率(LF)及LF/HF值均有所降低,其中SDNN、SDNN Index、三角指数、SDANN、LF及LF/HF值明显低于对照组(P<0.05).结论 CA患者心率变异性各指标下降,提示心脏自主神经功能障碍,迷走神经及交感神经活性均减弱,且以交感神经活性减弱为主.     

室上性心动过速发作前后心率变异的观察

分析21例SVT发作前后5min心率变异性旨在阐明植物神经系统异常在SVT发作中的作用。结果显示SVT发作前SDNN明显降低,LF、LFP、LF/HF明显升高,HF、HFP明显降低,LF/HF与SVT持续时间呈正相关(r=0.54,P<0.05 。)提示SVT发作前交感-迷走神经平衡向着交感神经张力增高,迷走神经张力消退的方向偏移,使SVT易于发作和持续。     

自主神经在阵发性房颤发生与维持中的作用机制

目的探讨交感神经和迷走神经在阵发性房颤发生中的作用及维持过程中的机制。方法利用Poincare散点图为工具,区分阵发性房颤的不同类型。通过对阵发性房颤病人发作前行动态心电图监测,并与健康志愿者进行比较,通过动态心电图分析发作前交感神经和迷走神经张力变化,监测窦性心搏RR间期的标准差(SDNN)、相邻RR间期差值的均方根(rMSSD)、SDNN指数(SDNN Index)、心率变异三角指数(HRVTI)、相邻NN之差50ms的个数占总窦性心搏个数的百分比(PNN50)、低频(LF)、高频(HF)、低频高频比值(LF/HF)前后变化。结果 100例房颤病人,迷走型房颤33例,交感型房颤67例。根据Poincare散点图形态,将房颤分为星形、椭圆形、棒球杆形、不规则形,100例房颤病人中星形63例,椭圆形13例,不规则形24例。交感型房颤和迷走型房颤与健康志愿者比较神经张力变化明显。交感型房颤病人LF、LF/HF均有明显变化,差异有统计学意义(P0.05);LF发作前30min~45min达到峰值。迷走型房颤病人HF、LF/HF与健康志愿者比较,差异有统计学意义(P0.05);HF发作前15 min明显增高;迷走型房颤发生前,HF、LF/HF较正常人差异明显,差异有统计学意义(P0.05)。结论阵发性房颤的发生与自主神经功能、心率变异性关系密切。     

射频消融术后心脏自主神经的变化对房颤早期复发的影响

目的:通过心率变异性分析,探讨左房环肺静脉消融术对自主神经系统的影响及其与心房颤动(房颤)早期复发的关系。方法:阵发性房颤患者90例,均接受CARTO指导下左房环肺静脉电隔离射频消融术。在术前3 d及术后3 d进行12导联动态心电图(Holter)监测,根据术后随访结果将患者分为房颤复发组(n=38例)和无复发组(n=52例)。并记录两组的平均心率(MeanHR),心率变异性(heart rate variability,HRV)分析,包括时域指标SDNN、SDANN、rMSSD、PNN50,频域指标W、LF、HF、LF/HF,进行比较。结果:90例患者均达到肺静脉电隔离。术后反应迷走神经及交感神经张力的指标均显著降低;在无复发组,反应迷走神经张力的HF降低更显著,LF/HF升高,其它HRV指标均显著降低;在复发组,MeanHR升高,反应交感神经张力的LF显著降低,LF/HF降低。结论:降低迷走神经张力,可能会抑制阵发性房颤患者左房环肺静脉消融术后的早期复发。     

正常人心率变异性的性别差异及生理节奏

检测60例正常人的24h心率变异性(HRV),分析性别、昼夜时辰的变化。表明代表交感神经和迷走神经活性平衡的参量LF/HF,女性显著低于男性,提示男性交感神经活性高于女性,和/或女性的迷走神经活性高于男性。夜间反映迷走神经活性的参量(如HF、rMSSD及pNN_(50))显著升高,与总功率密切相关的SDNN有较轻程度的下降。平均RR间期、rMSSD、pNN_(50)及SDNN有明显的时辰变化规律,起床后均显著降低。     

特发性室性心动过速发作前、后心率变异性变化

目的 分析特发性室性心动过速发作前、后心率变异性变化,探讨室速与自主神经功能的关系.方法 分析29例无器质性心脏病的特发性室速患者40阵次室速发作前、后1h心率变异指标.结果 室速发作前,SDANN、SDNN、PNN50、HF均降低,LF和LF/HF升高（P＜0.05）.结论 特发性室速患者存在自主神经功能失常,室速发作前交感神经张力增强,迷走神经张力降低.     

阵发性心房颤动发作前后心率变异性的变化

目的探索自主神经活动在阵发性心房颤动中的作用.方法在动态心电图上测量分析了25例阵发性房颤患者53阵次心房颤动发作前后及白天(6:00～22:00)和夜间(22:00～6:00)的心率变异指标(SDNN、LF、HF、LF/HF)的变化.结果房颤发作前1h SDNN、HF较终止后1h显著升高(p＜0.01),LF/HF显著降低(p＜0.01),LF无变化;LF、HF白天均高于夜间(分别为p＜0.05和p＜0.01),夜晚LF高于HF(p＜0.05),白天与夜间SDNN、LF/HF无差异,白天LF与HF无差异.结论阵发性心房颤动患者存在着明显的自主神经功能失常,特别是白天迷走神经张力增强;迷走神经张力增强是阵发性房颤的重要原因.     

慢性充血性心力衰竭患者心率变异性与甲状腺激素的关系

目的 探讨心力衰竭(心衰)患者心率变异性与甲状腺激素的关系.方法 采用时域和频域2种分析方法,对46例心衰患者及30例非心衰患者进行分析,同时测定甲状腺激素水平.结果 心衰患者24 h正常RR间期标准差(SDNN)、相邻正常RR间期差值的均方根值(rMSSD)、频域分析高频部分(HF)及低频部分(LF)均降低(P＜0.05),而低频部分与高频部分之比值(LF/HF)升高(P＜0.001).结论 心衰患者交感神经及迷走神经的调节功能明显受损,交感神经张力相对升高.伴有甲状腺激素紊乱的心衰患者有更严重的交感、迷走神经双重损害.提示纠正甲状腺激素紊乱,可能会使心衰患者心率变异性有一定程度的改善.     

基于心率变异性、心室晚电位评价温胆片对频发室性早搏的治疗作用

目的观察温胆片对频发室性早搏病人心率变异性(HRV)、心室晚电位(VLP)的影响,评价其治疗室性早搏的临床疗效。方法 60例符合24h动态心电图诊断的频发室性早搏病人,随机分为治疗组及对照组,每组30例。治疗组以温胆片(4粒,每日3次)口服,对照组以美托洛尔(25mg,每日2次),疗程4周,对比两组治疗前后HRV指标变化,包括时域指标(SDNN、rMSSD、pNN50)和频域指标(LF、HF、LH/HF);观察两组治疗前后VLP指标变化(包括TQRS、LAS40、RMS40)及VLP阳性患者的转阴率。结果与治疗前相比,两组治疗后SDNN、rMSSD、pNN50、HF均有显著升高(P0.05或P0.01),LF、LF/HF则明显降低(P0.05)。治疗后,TQRS、LAS40较前缩短,而RMS40较前增高(P0.05),治疗组及对照组对频发室性早搏VLP阳性患者转阴率分别为57.1%和75.0%。治疗组与对照组治疗室性早搏总有效率分别为70.0%和66.7%。结论温胆片能有效治疗频发室性早搏,其不仅可以改善心率变异性,而且可以通过缩短TQRS、LAS,提高RMS对VLP阳性病人有一定的转阴作用而改善频发室性早搏病人的预后,推测其机制可能同提高心脏迷走神经张力,抑制交感神经张力,改善心脏自主神经失衡状态有关。     

Utilization of Nerve Conduction Studies for the Diagnosis of Polyneuropathy in Patients with Diabetes: A Retrospective Analysis of a Large Patient Series

Background

Diabetic polyneuropathy (DPN) is a disabling complication of diabetes mellitus. A population-based analysis of physician utilization of nerve conduction studies (NCS) for the assessment of DPN was conducted.

Methods

All electrodiagnostic encounters over a 30-month period using a computer-based neurodiagnostic instrument linked to a data registry were analyzed retrospectively. The DPN case definition was abnormal sural and peroneal nerve conduction.

Results

The study cohort consisted of a total of 63,779 electrodiagnostic encounters performed by 3468 physician practices. Primary care and internal medicine physicians represented 80.1% of the practices and accounted for 65.7% of the encounters. Endocrinologists represented 4.6% of the practices and 20.1% of the encounters. The demographics of patients were 52.7% female; 63.4±11.8 (mean±standard deviation) years (age); 168.1±10.9cm (height); 92.2±22.6 kg (weight); and 32.6±7.2 kg/m² (body mass index). The most common peroneal abnormality was F-wave latency (33.6%). The sural nerve response latency and amplitude parameters had similar abnormality rates (58.3 and 62.7%). DPN was identified in 52.6% of the encounters; in another 19.3% no neuropathy was found.

Conclusions

For over 70% of the patients, the specific diagnostic question of the presence of DPN was addressed by NCS with evidence-based criteria. The demographic features were strongly associated with risk of diabetes and DPN, suggesting that NCS were applied to appropriate demographic subgroups. The rate of DPN was also comparable to levels seen by academic electromyography laboratories. In 32.6% of the encounters the NCS suggested a posttest diagnosis other than DPN. This rate was similar to the results of referral to traditional electromyography laboratories. This study demonstrated that NCS using computer-based electrodiagnostic equipment was a suitable tool for the diagnosis of DPN. Furthermore, this technology permits examination of DPN in large populations.     

小儿膀胱的神经分布

目的研究小儿膀胱的神经节和神经纤维分布情况。方法采用免疫组化及电镜技术对小儿膀胱壁全层标本进行观察和研究。结果小儿膀胱存在胆碱能神经节和胆碱能神经纤维，且各组织层次的分布差别较大，未观察到逼尿肌、颈部和三角区存在肾上腺素能神经和肽能神经纤维。结论副交感神经纤维(胆碱能神经纤维)在排尿生理中有重要作用。是否存在其它抑制性神经纤维，有待于进一步探讨。     

Biopsy of the posterior interosseous nerve: a low morbidity method for assessment of peripheral nerve disorders

Aims The sural nerve is the commonest peripheral nerve biopsied to help in the diagnosis of peripheral neuropathy of unknown cause. However, associated complications limit its use. The aim was, as an alternative, to asses biopsy of the terminal branch of the posterior interosseous nerve (PIN) in the forearm. Methods PIN pathology was morphometrically quantified in 10 male patients with Type 2 diabetes and compared with six PIN biopsy specimens taken post mortem from male cadavers with no history of neuropathy or trauma. Results The PIN biopsy procedure provides a long (approximately 3 cm) mono‐ or bifascicular nerve biopsy with generous epineurial tissue and adjacent vessels. Our results show a significantly lower myelinated fibre density in subjects with diabetes [5782 (3332–9060)/mm²] compared with autopsy control material [9256 (6593–12 935)/mm², P < 0.007]. No postoperative discomfort or complications were encountered. Conclusions A reduction in myelinated fibre density has previously been shown to be a clinically meaningful measure of neuropathy in diabetic patients. We demonstrate similar findings using the PIN biopsy. The PIN biopsy procedure fulfils the criteria for nerve biopsy and was well tolerated by the patients. It may be a possible alternative to sural nerve biopsy to allow for diagnosis of neuropathy.     

胆囊收缩素在胃电节律失常中的作用及其神经病理学机制

目的：探讨胆囊收缩素（CCK）在胃电节律失常中的作用及其神经学机制。方法：在建立胃窦肌间神经丛铺片方法的基础上,用酶组织化学与免疫细胞化学方法,观察胃电节律失常大鼠胃窦肌间神经丛内胆碱能（Ach）神经、一氧化氮合酶（NOS）神经及CCK神经的变化。结果：模型组和CCK组大鼠均出现胃电节律失常,异常节律指数及慢波频率变异系数均显著高于正常组（P＜0．01）;模型组和CCK组NOS神经显著增加,Ach神经含量显著减少（P＜0．01）。结论：外源性及内源性CCK增加,能诱发胃电节律失常。CCK通过激活NOS,产生胃电节律失常。胃窦肌间神经丛神经中CCK及NOS神经含量异常增加,Ach神经减少是发生胃电节律失常的神经病理学机制之一。     

Peripheral neuropathies of the forearm and hand in rheumatoid arthritis: diagnosis and options for treatment

Although the clinical hallmark of rheumatoid arthritis (RA) involves inflammatory joint disease, extra-articular manifestations may be evident in 20% of patients. Among them neurologic features involving both the peripheral and central nervous system are one of the more common, but little has been noticed about it in clinic. The same mechanisms participating in joint destruction, synovial inflammation, and vasculitis contribute to the various RA neurological complications. In this article, we reviewed clinical outcomes of peripheral neuropathies of the upper extremity associated with RA and discussed the proper diagnosis and operative indication. Magnetic resonance imaging and electrophysiological examination are the best tools to lead the final diagnosis of nerve palsy secondary to RA synovial cyst. Such neuropathies require consideration in the differential diagnosis of wrist and hand disability. Surgical decompression is recommended at prompt timing if neurophysiologic studies demonstrate denervation or significant motor abnormalities, or sensory symptoms progress despite adequate medication.     

吻合口位置对周围神经端侧吻合术后神经再生的影响

目的观察吻合口位置对神经端侧吻合术后再生神经的影响。方法取新西兰大白兔58只,随机选10只为定位组,行胫神经干功能束鉴定,确定运动神经纤维集中、混合神经集中位置;余48只随机分为A、B组,各24只,切断腓总神经远端,并与外膜开窗的胫神经端侧缝合。A组为实验组,吻合口位于运动神经纤维集中处;B组为对照组,吻合口位于混合神经纤维集中处。于术后1、2、3个月,A、B组每次各取8只,于吻合口近端行电生理检测,取吻合口远端0.5 cm处的腓总神经进行组织学及抗神经丝蛋白免疫组化检测。结果光镜下可区分有髓神经纤维及无髓神经纤维团块并定位。随着术后时间延长,A、B组再生神经诱发电位的潜伏期逐渐缩短,波幅逐渐增大、肌湿重和肌纤维截面积逐渐增大、腓总神经有髓神经纤维数和神经束截面积显著增大,抗神经丝免疫组化阳性表达逐渐增强,且A组均优于B组。结论周围神经端侧吻合时,吻合口位于运动神经束集中处,其再生的运动神经纤维数目多,质量高,所支配肌肉的功能恢复较好。     

躯体传入神经刺激与室性心律失常

室性心律失常是临床上发病率和致死率均较高的疾病,其治疗方式主要涉及药物治疗、植入型心律转复除颤器及射频消融治疗,这些治疗方式的联合应用已极大地改善了患者的生活质量及预后,但仍不能完全治愈其发生。研究指出室性心律失常与自主神经系统存在密切的关系,交感神经-副交感神经活性的失衡可诱发或抑制室性心律失常的发作,躯体传入神经刺激可能调节自主神经系统进而干预心律失常事件的发生。现综述自主神经系统、躯体传入神经刺激与室性心律失常之间的关系。     

电激心脏植物神经对心率变异性的影响

大量文献表明，心率变异性（HRV）功率谱的高频成份（HF）是迷走神经活动对窦房结影响程度大小的标志；HRV功率谱的低频成份（LF）表示了心交感神经或心交感与迷走神经共同对窦房结的紧张作用；在很多生理和病理情况下，RF（LF／HF的比值）代表了心交感迷走神经对窦房结调制的均衡状态。本文直接使用方波电刺激狗的心交感神经或迷走神经128S，观察到刺激心交感神经时的平均心率（HR）、LF和HF较刺激前无显著性变化，但平均心率的标准差（SD）和RF却显著增大；刺激心迷走神经时RF明显降低，其余指标与刺激前相比，无明显变化。说明直接使用电刺激心交感或迷走神经，可造成对窦房结调制作用的均衡状态改变。     

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Additionally, translational models are required to identify stimulation parameters that can be transferred to clinical applications of bioelectronic medicines. Here, we performed neuroanatomical and functional comparison of the mouse, rat, pig, and human splenic nerve using in vivo and ex vivo preparations. The pig was identified as a more suitable model of the human splenic innervation. Using functional electrophysiology, we developed a clinically relevant marker of splenic nerve engagement through stimulation-dependent reversible reduction in local blood flow. Translation of immunomodulatory mechanisms were then assessed using pig splenocytes and two models of acute inflammation in anesthetized pigs. The pig splenic nerve was shown to locally release noradrenaline upon stimulation, which was able to modulate cytokine production by pig splenocytes. Splenic nerve stimulation was found to promote cardiovascular protection as well as cytokine modulation in a high- and a low-dose lipopolysaccharide model, respectively. Importantly, splenic nerve–induced cytokine modulation was reproduced by stimulating the efferent trunk of the cervical vagus nerve. This work demonstrates that immune responses can be modulated by stimulation of spleen-targeted autonomic nerves in translational species and identifies splenic nerve stimulation parameters and biomarkers that are directly applicable to humans due to anatomical and electrophysiological similarities.

The inflammatory status of the body is monitored and regulated through the neuroimmune axis, connecting the brain to the immune system via both humoral and neural pathways (1–3). In particular, the inflammatory reflex (3) controls systemic immune responses; detection of inflammatory stimuli in the periphery is communicated to the brain that activates outflow of neural signals to promote peripheral immune responses proportional to the threat. Studies in rodent models have identified the cholinergic anti-inflammatory pathway (CAIP) as the brain’s efferent response to infection and inflammation through peripheral neurotransmitters released in lymphoid organs, mainly the spleen (4, 5). Within this pathway, the peripheral connection between the vagus nerve (VN), the splenic nerve (SpN), and its terminal release of noradrenaline (NA) into the spleen have been identified as crucial components of this neural circuit (6–8) (SI Appendix, Fig. S1A).Importantly, the CAIP can be harnessed to promote immune control. Activation of the cervical VN by electrical stimulation (vagus nerve stimulation—VNS; SI Appendix, Fig. S1A) has been shown to be effective in reducing lipopolysaccharide (LPS)-induced levels of tumor necrosis factor alpha (TNF-α) (4, 6, 7) and in preclinical rodent models of chronic inflammatory diseases (9, 10). Murine models have generally been used to demonstrate biological proof of concepts of novel neuromodulation therapies in this and other contexts. However, the development of clinical bioelectronic medicines requires the accurate estimation and validation of stimulation parameters in a histologically, surgically, and anatomically relevant model to define device and therapy requirements. The translation of stimulation parameters from rodent to human is hampered by anatomical (e.g., size of nerves), histological (e.g., number of axons, connective tissue thickness, proportion of adipose tissue), and physiological (e.g., immunological) differences. Therefore, it is suggested that the use of large animal models, human tissues, and in silico modeling are more appropriate for the optimization and scaling of human-relevant parameters (11, 12).Although early clinical feasibility studies have provided preliminary evidence of immunomodulatory effects of VNS in patients (13, 14), clear demonstration of the translation of the splenic anti-inflammatory pathway in clinically relevant species is currently lacking in the literature. The VN has a functionally and anatomically complex composition. In animals and humans, the VN contains both afferent and efferent axons of varying size (large, medium, and small) and degree of myelination (heavily myelinated, lightly myelinated, and unmyelinated axons) innervating multiple organs and muscles (15). As a consequence, currently used VNS results in activation of off-target circuits (SI Appendix, Fig. S1A) that can cause dysphonia, coughing, hoarseness, pain, and dyspnea (16–18); in some patients, these can be managed and can also improve over time (18). Further, it remains unclear which axons (efferent versus afferent, myelinated versus unmyelinated) within the VN relay immunomodulatory signals to peripheral organs (19, 20). As a result, it is difficult to optimize the stimulation parameters necessary to activate axons within the VN which carry signals to the spleen. Typically, clinical parameters are selected based on the individual patient’s tolerance of off-target effects (13, 21) without direct evidence of activation of the anti-inflammatory pathway because of a lack of an organ-specific biomarker. Since the SpN directly transmits neural signals to the spleen and is the fundamental nodal circuit in mediating the anti-inflammatory response (22), SpN stimulation (SpNS) may represent an alternative modality providing the opportunity for near-organ modulation of the immune system (SI Appendix, Fig. S1 B and C). Proof of concept experiments in rodents have shown that immune responses can indeed be modulated by stimulation of the SpN with comparable cytokine suppressive effects to VNS (7, 8, 23).Here, we anatomically, histologically, and functionally compared the mouse, rat, pig, and human SpN, demonstrating the superiority of the pig as a translational model of the human SpN. We then performed functional in vivo pig electrophysiological studies to identify organ-specific physiological biomarkers that can be used to assess nerve engagement and to refine stimulation parameters. Finally, we assessed the large animal translation of the spleen-dependent anti-inflammatory pathway in the pig using in vitro splenocyte preparations together with two in vivo models of acute inflammation.     

化学去细胞异体神经移植修复鼠全面神经的实验研究

目的利用具有＂一主干多分支＂特征的化学去细胞同种异体神经（CEAN）修复大鼠面神经缺损并评价修复效果。方法取成年SD大鼠双侧面神经进行去细胞同种异体面神经制备和自体面神经冻融处理并进行结构评价。取成年雄性SD大鼠30只,制备大鼠左侧面神经10 mm缺损模型,随机分成3组（n=10）,分别为采用自体神经移植组（A组）、去细胞同种异体面神经移植（CEANA）组（B组）和自体神经液氮冷冻组（C组）,术后行大体观察和组织学观察。结果利用化学法可制备出保留天然成分和空间结构的具有＂一干多支＂特征的CEAN。术后12周,A组、B组有髓神经纤维总数均优于C组（P〈0.05）,A组与B组比较差异无统计学意义（P〉0.05）。结论保留天然成分和空间结构的具有＂一干多支＂特征的CEANA可用于修复大鼠全面神经缺损的治疗,具有同自体神经移植相似的修复效果。