Loss of anti-arrhythmic effect of vagal nerve stimulation on ischemia-induced ventricular tachyarrhythmia in aged rats

Reduced vagal activity is associated with increased risk for life-threatening arrhythmia during myocardial ischemia (MI); conversely, the increase in vagal tone may provide protective effect against ventricular arrhythmias. In fact, vagal nerve stimulation (VNS) exerted an anti-arrhythmic effect by preserving connexin 43 (Cx43), a gap junction protein in ventricles, in a rat model of MI. We investigated the effects of VNS on ventricular tachyarrhythmia during acute MI and the expression of Cx43 in aged rats. Both adult (3-4 months) and aged (≥ 24 months) male rats were subjected to ischemia of 30 min. VNS was applied before ischemia either alone or in combination with atropine (0.5 mg/kg) or carbenoxolone, a gap junction inhibitor (10 mg/kg). During the 30-min ischemia, the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) was higher in aged rats compared with adult rats. VNS significantly suppressed VT and VF in adult rats and these effects were eliminated by atropine or carbenoxolone. In contrast, VNS did not suppress VT and VF in the aged rats. Moreover, ischemia did not change the expression levels of total Cx43 protein in adult and aged rat ventricles. However, the expression level of total Cx43 protein was two times lower in sham-operated aged rats than that in sham-operated adult rats. Thus, in aged rats, loss of anti-arrhythmic effect of VNS is associated with reduced expression of Cx43 protein. These findings suggest that Cx43 may be an important target for inhibiting ischemia-induced VT in adult patients but not in aged patients.     

体外膈神经电刺激对脑卒中患者呼吸功能的影响

目的探讨体外膈神经电刺激对脑卒中患者呼吸功能的影响。方法选择2020年8月至2021年5月恢复期脑卒中患者50例,按照随机数字表法分为干预组及对照组各25例。两组均予以常规康复,干预组在此基础上增加体外膈神经电刺激。分别于治疗前、治疗4周后评估膈肌功能、肺通气功能、呼吸肌肌力。结果治疗4周后,两组患者的膈肌活动度、用力肺活量、第1秒用力呼气容积、峰值呼气流速、最大呼气压、最大吸气压均较治疗前显著提高,且干预组较对照组提高更为明显,差异均有统计学意义(P<0.05)。结论体外膈神经电刺激可显著改善脑卒中患者的呼吸功能。     

Impairment of vagal function in reflux oesophagitis

Autonomic nervous function in reflux oesophagitis was assessed by measuring the response of the lower oesophageal sphincter to abdominal compression, gastric secretory response to insulin-induced hypoglycaemia and pulse rate variability with respiration. Rise in intra-abdominal pressure normally causes an increase in lower oesophageal sphincter pressure through a vagally mediated mechanism. In 59 of 83 patients with reflux oesophagitis the sphincter response was subnormal, and this was commoner in older patients but was unrelated to the presence of a hiatal hernia. During oesophageal acid perfusion, the onset of pain, but not that of disordered motility, was delayed in those with an abnormal sphincter response suggesting impairment of afferent autonomic function. Efferent gastric vagal function, assessed by the gastric secretory response to insulin induced hypoglycaemia and expressed as a ratio of the maximal acid output after pentagastrin, was subnormal in 15 of 27 patients with reflux oesophagitis. Pulse rate variability with deep respiration, an indicator of one aspect of non-alimentary vagal function, was subnormal in 18 of 62 patients with reflux oesophagitis. There was no correlation between abnormalities in these three tests of vagal function or with the severity of oesophagitis. These findings suggest that vagal impairment is common in reflux oesophagitis. As impairment of vagal function is not confined to the alimentary system it is unlikely to be simply a consequence of reflux oesophagitis and may be important in the pathogenesis of gastro-oesophageal reflux.     

神经生长液促大鼠坐骨神经再生的实验研究

目的评价一种新型中药-神经生长液对大鼠坐骨神经损伤后神经再生的影响。方法SD大鼠50只雌雄各半,采用随机数字表法将其随机分成5组:神经生长液低、中、高剂量组,弥可保组和空白对照组。采用坐骨神经夹伤模型,于术后每5d测定坐骨神经功能指数(sciaticnerveindex,SFI),术后第20天行电生理,组织学检测及超微结构观察。结果术后5d时实验组(-72±9)与对照组(-79±8)间SFI差异无显著性意义(F=1.58,P>0.05),10d时高剂量组(-60±9)和弥可保组(-61±7)优于对照组(-75±7)(F=5.1,P<0.05),15d和20d时低、中、高剂量组及弥可保组均优于对照组(F=6.83和9.92,P<0.05)。坐骨神经干动作电位传导速度,小腿三头肌最大收缩力检测,及脊髓前角运动神经元记数、再生有髓纤维数、肌细胞截面积等指标神经生长液低、中、高剂量组及弥可保组均优于空白对照组(F=26.29,51.35,7.86,37.38,11.11,P<0.05)。超微结构观察实验组有髓神经纤维的髓鞘形态、厚度、成熟度均优于对照组,变性纤维的数目少于对照组。结论神经生长液能促进周围神经再生及功能的恢复。     

高压氧对实验性大鼠脑卒中后RhoA表达及神经功能的影响

目的探讨高压氧（HBO）治疗对MCAO大鼠脑组织RhoA蛋白的表达强度变化和神经功能评分的影响。方法将126只健康的雄性SD大鼠随机分为假手术组、缺血2h再灌注HBO治疗组（治疗组）和缺血再灌注未作处理组（对照组），每组大鼠42只。用线栓法制备大鼠大脑中动脉闭塞（MCAO）模型，缺血2h后再灌注。评定各组脑组织造模后不同时间点RhoA蛋白的表达变化、不同的时间点神经功能评分改变。结果假手术组双侧大脑皮质和基底节区可见RhoA蛋白弱阳性表达，术后各时间点表达强度无明显差异。与假手术组比较，治疗组和对照组缺血侧皮质神经元细胞和神经胶质细胞RhoA蛋白表达在缺血再灌注后6h开始增加，随着时间的延长，RhoA蛋白的表达进行性增加，至48h达到高峰之后逐渐下降，到第14天仍明显增高。治疗组和对照组两组各时点RhoA蛋白阳性细胞平均光密度（AOD）比较差异有统计学意义（P〈0．01）：治疗组和对照组两组间比较，治疗组各时间点神经功能缺损评分均低于对照组，到术后第14天时，2组神经功能缺损评分有统计学意义（P〈0．05）。结论（1）脑缺血后急性期和恢复期存在RhoA活动的增强，提示缺血性脑损伤启动了内源性抑制损伤后神经功能康复的机制。（2）HBO治疗可降低RhoA蛋白在脑缺血后各时间点的阳性表达，和神经功能评分改变相一致，提示HBO治疗有调节RhoA信号传导通路活动的作用，这可能是其促进脑损伤后神经功能康复的机制之一。     

甲状腺激素人工神经桥接大鼠坐骨神经对其功能的修复作用

目的:观察自行设计构建的甲状腺激素人工神经(PDLLA-T3)桥接大鼠坐骨神经缺损后神经功能的恢复情况。方法:实验设自体神经移植组和不含甲状腺激素的PDLLA材料组作为PDLLA-T3的对照组,大鼠共80只,左侧坐骨神经均为手术组,右侧为正常对照,在2周、1,2个月3个时相点分别进行电生理、肌湿重恢复率和坐骨神经功能指数的测定,电生理测神经的传导速度和潜伏期,2个月时测定肌湿重恢复率。结果:潜伏期和神经传导速度及坐骨神经功能指数(sciaticnervefunc-tionindex,SFI)值在2周时,各组均无显著性差异。1个月后,PDLLA-T3组恢复好于PDLLA组,各组之间差异有显著性意义(P<0.05)。2个月后PDLLA-T3组潜伏期恢复到2.14ms,传导速度29.97m/s,肌湿重恢复率达40.47%,SFI值37.16,均好于PDLLA组(P<0.01)。结论:PDLLA-T3作为神经组织工程材料,能促进大鼠坐骨神经功能的恢复。     

The effect of glucagon on esophageal peristalsis and clearance

The effect of 0.5 mg intravenous glucagon on esophageal peristalsis and transit of water and barium was studied in nine healthy subjects by concurrent videofluoroscopy and manometry.Glucagon lowered manometric peristaltic amplitude in both mid- and distal esophagus. This reached significance (p=0.0075) in the distal 3 cm of the esophagus 2 min after the injection. The efficiency of esophageal stripping was also reduced (increased proximal escape on fluoroscopy), and became significant (p=0.05) at 2 min after the injection of glucagon.     

Influence of successive vagal stimulations on contractions in esophageal smooth muscle of opossum.

Studies were performed in anesthetized opossums to investigate the influence of successive vagal stimuli on esophageal contractions. Mechanical activity was recorded manometrically 5 cm above the lower esophageal sphincter. Contractions in the esophagus were evoked by electrical stimuli of 2.5 mA, and 1-ms pulse duration applied to the cervical vagi, at various train durations and frequencies. Paired or multiple stimuli of 1-s train length were also tested at different interstimulus intervals (ISI). Paired stimuli at an ISI of less than or equal to 3 s and at a frequency of less than or equal to 10 Hz showed refractoriness, i.e., the contractions to the first stimulus inhibited the contraction to the second stimulus. A frequency of 50 Hz showed initial inhibition, i.e., the second stimulus inhibited the contraction to the first stimulus. Repetitive stimuli applied at a rate of 8/min (ISI 6.5 s) evoked contractions to each stimulus. At 15/min, every second or third contraction was inhibited. With stimuli applied at 30/min, contractions occurred only in response to the first and/or the last stimulus; depending upon the frequency of vagal stimulation. The intervening stimuli did not evoke any contractions. A long train stimulus produced an initial, a terminal, or both contractions depending on the stimulation value. These studies show that (a) vagal efferent stimulation causes initial inhibition and refractoriness in the esophageal smooth muscle; (b) the degree of initial inhibition increases with increasing frequency of stimulation; (c) the occurrence of contractions only at the onset and the end of a long train stimulus may be due to the influence of initial inhibition and refractoriness.     

Modulation of esophageal peristalsis by vagal efferent stimulation in opossum.

Experiments were performed on anesthetized opossums to study the influence of vagal efferent stimulation on peristalsis in the esophageal smooth muscle using various stimulus parameters. Current intensity, pulse duration, frequency, and train duration were varied systematically. Electrical and mechanical activities were recorded simultaneously at 5, 3, and 1 cm above the lower esophageal sphincter (LES). Vagal efferent stimulation produced a spike burst and contraction with a latency after the termination of the stimulus. This latency varied at different sites with the same stimulus parameters. For example, a stimulus of 5 mA, 0.5 ms, 10 Hz, and 1-s train produced latencies for the electrical response of 1.48 +/- 0.04, 2.2 +/- 0.12, and 3.5 +/- 0.09 s (+/- SEM) at 5, 3, and 1 cm above LES, respectively. The differences in latency were statistically significant (P less than 0.01). The latency of response at any one site also changed with different stimulus parameters; e.g. at 1 cm above LES, the latency of electrical response at 10 Hz was 3.5 +/- 0.09 s, but at 20 Hz the latency was 2.01 +/- 0.06 s when current intensity, pulse, and train duration remained at 5 mA, 0.5 ms, and 1 s. This decrease in latency with increasing frequency was statistically significant (P less than 0.01). By changing stimulus parameters, antiperistalsis or peristalsis with different speeds of propagation could be induced. Antiperistalsis or simultaneous responses occurred near threshold stimulus parameters. Suprathreshold stimuli produced peristaltic responses. Speed of peristalsis in the distal esophagus was 1.82 +/- 0.08 cm/s with swallowing, which was not different from 1.98 +/- 0.14 cm/s (P greater than 0.05) with vagal stimulation of 5 mA, 0.5 ms, 10 Hz, and 1-s train. These studies suggest that: (a) peristalsis in the smooth muscle part of the esophagus can be explained entirely on the basis of peripheral mechanisms, and (b) the central nervous system may modulate the occurrence, polarity, and speed of propagation by modifying the intensity and frequency of vagal activation.     

胺碘酮联合迷走神经刺激对心律失常的疗效分析

目的研究胺碘酮联合迷走神经刺激法对于心律失常(主要为快速性心律失常)的疗效。方法将2009年至2011年心内科及急诊科收治的快速型心律失常的患者264例随机分成3组,分别使用单纯胺碘酮治疗、单纯迷走神经刺激治疗以及胺碘酮联合迷走神经刺激治疗的方法进行治疗。记录患者心率转复的时间以及转复后的心率,同时对患者进行12个月的随访,观察患者的复发以及远期并发症发生率。结果胺碘酮组转复率为77.3%,平均转复时间为(52.5±10.3)min;迷走神经组转复率为35.2%,平均转复时间为(11.5±4.7)min;联合组转复率为83.0%,平均转复时间为(23.5±6.2)min。联合组的转复率显著高于其余两组且平均转复时间较短,差异具有显著性(P<0.05)。此外胺碘酮组与联合组中房扑/颤、交界性、室性、室上性心动过速以及室扑/颤的转复率较高,且显著高于迷走神经组,其差异均具有统计学意义(P<0.05)。结论胺碘酮联合迷走神经刺激对于快速性心律失常的控制治疗具有转复效好、转复时间短的特点,此外其对室上性与室性心动过速的疗效更好。对于其他方法无法控制的顽固性室上性、室性心律失常可尝试使用此法治疗。     

The effect of vagus nerve stimulation on migraines

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.     

食管鳞癌中分泌性富含半胱氨酸的酸性蛋白基因差异表达分析

目的探讨分泌性富含半胱氨酸的酸性蛋白(SPARC)在食管鳞癌(ESCC)增殖、浸润、转移中的作用和意义。方法用半定量逆转录聚合酶链反应(RTPCR)分析SPARC在24份ESCC组织和其相邻的正常黏膜组织的差异表达量及基因表达变化趋势。用酶联免疫吸附试验(ELISA)检测40名正常对照者和32例ESCC患者手术前后血浆中SPARC水平变化。结果经RTPCR分析SPARC在24份配对标本中的表达,其中19份ESCC组织中的表达明显高于其配对的正常黏膜组织,5份差异表达不明显;而在不同分化程度组织中的表达差异无统计学意义(P=0.663),淋巴结转移组与未转移组的差异有统计学意义(P<0.05)。正常人血浆SPARC水平[(644±124)ng/ml]与ESCC术前患者[(613±119)ng/ml]的差异无统计学意义(P=0.829);ESCC患者术后1周血浆SPARC水平[(245±45)ng/ml]明显低于术前(P<0.01),而19例ESCC术前患者血浆SPARC水平与术后3个月[(661±182)ng/ml]的差异亦无统计学意义(P=0.935);不同分化程度的ESCC患者血浆SPARC水平差异无统计学意义(P>0.05)。结论组织中SPARC水平与ESCC的发生与发展密切相关,有淋巴结转移时SPARC表达升高,血浆SPARC水平对ESCC诊治无指导意义。     

Nature of the vagal inhibitory innervation to the lower esophageal sphincter.

The purpose of the present study was to investigate the nature of the vagal inhibitory innervation to the lower esophageal sphincter in the anesthetized opossum. Sphincter relaxation with electrical stimulation of the vagus was not antagonized by atropine, propranolol, phentolamine, or by catechloamine depletion with reserpine. A combination of atropine and propranolol was also ineffective, suggesting that the vagal inhibitory influences may be mediated by the noncholinergic, nonadrenergic neurons. To determine whether a synaptic link with nicotinic transmission was present, we investigated the effect of hexamethonium on vagal-stimulated lower esophageal sphincter relaxation. Hexamethonium in doses that completely antagonized the sphincter relaxation in response to a ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), did not block the sphincter relaxation in response to vagal stimulation at 10 pulses per second, and optimal frequency of stimulation. A combination of hexamethonium and catecholamine depletion was also ineffective, but hexamethonium plus atropine markedly antagonized sphincter relaxation (P less than 0.001). Moreover, 4-(m-chlorophenyl carbamoyloxy)-2-butyltrimethylammonium chloride (McN-A-343), a muscarinic ganglionic stimulant, also caused relaxation of the lower esophageal sphincter. We suggest from these results that: (a) pthe vagal inhibitory pathway to the sphincter consists of preganglionic fibers which synapse with postganglionic neurons: (b) the synaptic transmission is predominantly cholinergic and utilizes nicotinic as well as muscarinic receptors on the postganglionic neuron, and; (c) postganglionic neurons exert their influence on the sphincter by an unidentified inhibitory transmitter that is neither adrenergic nor cholinergic.