糖尿病大鼠胃肠动力及肌间神经丛形态学改变

目的 了解糖尿病大鼠胃肠动力障碍时，肌间神经丛有无形态学异常并探讨胃肠功能异常的机制。方法 30只大鼠分成对照组（10只）和糖尿病组（20只），糖尿病组用链脲佐菌素建立大鼠糖尿病模型，4个月后测定两组大鼠胃肠传输速率，并用酶组织化学方法观察回肠肌间神经丛内胆碱能和氮能神经的组织学改变。结果 糖尿病组大鼠胃肠传输速率明显延迟，回肠肌间神经丛内胆碱能神经元密度明显降低（P〈0．01），氮能神经节和氮能神经元的密度均显著升高（P〈0．05和P〈0．01）。结论 糖尿病大鼠小肠肌间神经丛内胆碱能神经减少，氮能神经增多，这可能是导致胃肠传输速率延迟的重要原因，由此引起小肠运动障碍。     

非睡眠状态房室传导阻滞22例临床分析

目的探讨非睡眠状态间歇出现的房室传导阻滞(AVB)的原因与临床意义。方法对22例在非睡眠状态间歇性出现Ⅰ度或Ⅱ度Ⅰ型房室传导阻滞病人的临床资料进行回顾性分析。结果Ⅰ度房室传导阻滞7例,Ⅱ度Ⅰ型房室传导阻滞15例,其中5例晚上睡眠加重,大多数于站立或活动(婴儿在哭闹后)或予阿托品或山莨菪碱口服后减轻。结论非睡眠状态下出现AVB原因较复杂,可以是迷走神经功能亢进或交感神经兴奋性低下等自主神经系统紊乱所致,可以是非心脏病变引起的迷走神经损伤,还可以是感染性心肌炎、心肌梗死、先天性心脏病等引起。     

Assessment of Beat-by-Beat Control of Heart Rate by the Autonomic Nervous System: Molecular Biology Techniques Are Necessary, But Not Sufficient

Neural Control of Heart Rate. Vagus nerve activity can change heart rate substantially within one cardiac cycle, and the chronotropic effects decay almost completely within one cardiac cycle after cessation of vagal activity. The ability of the vagus nerves to regulate heart rate beat by beat can be explained in large part by the speed at which the neural signal is transduced to a cardiac response and by the rapidity of the processes that restore the basal heart rate when vagal activity ceases. Currently, the question of whether the cardiac tells can transduce the sympathetic neural signals rapidly enough to implement beatwise regulation is controversial. Emphasis on the speed of the processes that initiate the responses may, however, be misplaced. Instead, the processes that terminate the responses to autonomic neural activity (especially those processes that remove the released neurotransmitters) are probably the main determinants of the ability of the vagal and sympathetic systems to affect beatwise control. The norepinephrine (NE) released from the sympathetic nerve endings is removed from the cardiac tissues much more slowly than is the acetylcholine that is released from the vagal terminals. As a consequence of the potential deleterious effects associated with the slow removal of NE, the cardiac neural control system has evolved such that the sympathetic nerves ordinarily release NE at a slow rate. Hence, changes in sympathetic neural activity can alter cardiac behavior only slightly from beat to beat. Hence, beatwise control of cardiac function would be negligible, regardless of how swiftly the sympathetic nerve impulse is transduced t o a change in cardiac-performance.     

Effect of Renal Denervation on the Development of Cellophane-Wrap Hypertension in Rabbits

The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervatton of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 ± 3 mmHg and 31 ± 3 mmHg in rabbits with innervated kidneys and 7 ± 2 mmHg and 26 ± 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.     

Pancreatic polypeptide response to a meal before and after cutting the extrinsic nerves of the upper gastrointestinal tract and the pancreas in the dog

The role of the sympathetic and parasympathetic innervation in the release of pancreatic polypeptide (PP) basally and in response to a meal was studied after stepwise extrinsic denervation of the pancreas and the upper gastrointestinal tract in conscious dogs with gastric fistulae. One set of seven dogs was fed a meat meal (35 g/kg body weight) before and after truncal vagotomy and after truncal vagotomy plus celiac and superior mesenteric ganglionectomy, ie, extrinsic denervation of the pancreas and the upper gastrointestinal tract. In another set of six dogs, only ganglionectomy was performed. Experiments were repeated in the presence of atropine (50 g/kg body weight, given as an intravenous bolus 60 min prior to the meal). Truncal vagotomy significantly (P<0.05) reduced the postprandial 120-min integrated plasma PP response (IPPPR) by 84% as compared to the prevagotomy response. Before truncal vagotomy, atropine significantly reduced the IPPPR by 57%. After truncal vagotomy, atropine completely abolished the residual PP response. Additional celiac and superior mesenteric ganglionectomy did not alter the IPPPR already reduced by truncal vagotomy. With the vagus nerves intact, ganglionectomy alone had no effect on the IPPPR whether or not atropine was given. These findings indicate that (1) the splanchnic nerves do not play a significant role in postprandial PP release and (2) that the vagus nerves are important mediators of the response to a meal. The effect of atropine on postprandial PP release after truncal vagotomy may be due to interruption of short enteropancreatic reflexes, suppression of the intrinsic cholinergic activity of the pancreas, or inhibition of hormonally induced PP release.     

胃电节律失常大鼠胃窦肌间神经丛胆碱能神经的改变

目的：探讨大鼠胃窦肌间神经丛胆碱能神经，氮能神经含量变化与胃电节律失常的关系。方法：63例大鼠随机分为正常对照组，胃电节律失常模型组和白芍组。饲养4周后记录并分析胃电信号，测定胃窦肌间神经丛胆碱能神经含量。结果：模型组胃电节律失常明显增加，胃窦肌间神经丛胆碱能神经含量减少；经白芍治疗后，胃电节律失常明显减少，胃窦肌间神经丛胆碱能神经含量恢复正常。结论：胃窦肌间神经丛的胆碱能神经与胃电节律关系密切，当胆碱能神经减少时，胃电节律失常明显增加。     

Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans

Aims/hypothesis This study examined whether autonomic mechanisms contribute to adaptively increased insulin secretion in insulin-resistant humans, as has been proposed from studies in animals. Methods Insulin secretion was evaluated before and after induction of insulin resistance with or without interruption of neural transmission. Insulin resistance was induced by dexamethasone (15 mg given over 3 days) in nine healthy women (age 67 years, BMI 25.2 ± 3.4 kg/m², fasting glucose 5.1 ± 0.4 mmol/l, fasting insulin 46 ± 6 pmol/l). Insulin secretion was evaluated as the insulin response to intravenous arginine (5 g) injected at fasting glucose and after raising glucose to 13 to15 mmol/l or to >28 mmol/l. Neural transmission across the ganglia was interrupted by infusion of trimethaphan (0.3–0.6 mg kg⁻¹ min⁻¹). Results As an indication of insulin resistance, dexamethasone increased fasting insulin (to 75 ± 8 pmol/l, p < 0.001) without significantly affecting fasting glucose. Arginine-induced insulin secretion was increased by dexamethasone at all glucose levels (by 64 ± 12% at fasting glucose, by 80 ± 19% at 13–15 mmol glucose and by 43 ± 12% at >28 mmol glucose; p <0.001 for all). During dexamethasone-induced insulin resistance, trimethaphan reduced the insulin response to arginine at all three glucose levels. The augmentation of the arginine-induced insulin responses by dexamethasone-induced insulin resistance was reduced by trimethaphan by 48 ± 6% at fasting glucose, 61 ± 8% at 13–15 mmol/l glucose and 62 ± 8% at >28 mmol/l glucose (p < 0.001 for all). In contrast, trimethaphan did not affect insulin secretion before dexamethasone was given. Conclusions/interpretations Autonomic mechanisms contribute to the adaptative increase in insulin secretion in dexamethasone-induced insulin resistance in healthy participants.     

Rat bladder in the early stages of streptozotocin-induced diabetes: adrenergic and cholinergic innervation

Summary The adrenergic and cholinergic innervation of the bladder was studied in streptozotocin-diabetic rats. The presence of hypertrophy and distension in the diabetic bladders necessitates care in assessing changes occurring in the nerves, factors which are also relevant to clinical histochemical studies. Biochemical assays of cholinergic enzymes revealed decreased activities per g wet weight tissue. However, the total activities of choline acetyltransferase and acetylcholinesterase per whole bladder were significantly increased after 2 weeks of diabetes with greater changes by 8 weeks. Total dopamine levels per bladder were significantly higher than in control rats in the 2-week but not the 8-week group of animals; this may indicate an initial increase in adrenergic nerve activity. There was no impairment in the ability of the detrusor muscle to respond to noradrenaline, acetylcholine or to cholinergic nerve stimulation. Shortly after induction of diabetes streptozotocin-treated rats display polyuria. It is proposed that the activity of the bladder is therefore stimulated to allow greater volumes of urine to be passed. The results are discussed in relation to human diabetes mellitus where clinical studies have implicated a neuropathic origin to bladder dysfunction.     

脊神经刺激对星状神经节功能的影响

目的观察低强度脊神经刺激(SCS)对星状神经节功能的影响。方法用随机数字表法将12只成年犬分为两组:实验组6只,用90%阈电压(阈电压定义为刺激胸1-胸2脊神经引起肌肉震颤的最低电压数值)进行低强度SCS,持续6 h;对照组6只,同等强度刺激同水平脊髓节段不会引起肌肉震颤的部位,持续6 h。记录基础状态、2、4和6 h末递增电压刺激左侧星状神经节(LSG)、右侧星状神经节(RSG)时的血压或心率变化。以刺激电压作为横坐标,血压或心率变化的最大百分比作为纵坐标绘出电压-血压反应曲线及电压-心率反应曲线,其中电压-血压反应曲线代表LSG功能曲线,电压-心率曲线则代表RSG功能曲线。结果低强度SCS刺激6 h使电压-血压反应曲线及电压-心率反应曲线逐渐钝化,使同等电压刺激引起的最大血压及最大心率变化逐渐降低;而对照组6 h低强度SCS对LSG的电压-血压反应曲线及RSG的电压-心率反应曲线无明显影响。结论 6 h低强度SCS可以明显抑制LSG及RSG的功能。     

Innervation of the liver: morphology and function

Abstract: Although it has been known for many years that the liver receives a nerve supply, it is only with the advent of immunohistochemistry that this innervation has been analysed in depth. It is now appreciated not only that many different nerve types are present, but also that there are significant differences between species, especially in the degree of parenchymal innervation. This has stimulated more detailed investigation of the innervation of the human liver in both health and disease. At the same time, functional studies have been underlining the important roles that these nerves play in processes as diverse as osmoreception and liver regeneration. This article briefly reviews current understanding of the morphology and functions of the hepatic nerve supply.     

Neuronal control of coronary blood flow

Controversies on acetylcholine-induced increases or decreases in coronary blood flow arise from obvious species differences, the role of endothelium in mediating vascular smooth muscle responses, and the marked negative chronotropic and inotropic effects of acetylcholine. In man, there appears to be a predominant dilation of intact epicardial coronary arteries and a constriction of artherosclerotic segments. However, at present there is no evidence for a vagal initiation of myocardial ischemia. Coronary vascular β-adrenergic receptors mediate dilation, but appear to be functionally insignificant during sympathetic activation. The β-adrenergic mechanism contributing to myocardial ischemia are indirect, mediated by a tachycardia-related redistribution of blood flow away from the ischemic myocardium. α-Adrenergic receptors mediating epicardial coronary artery constriction in experimental studies appear not to be responsible for the initiation of ischemia in patients with angina at rest. However, α-adrenergic constriction of coronary resistance vessels resulting in the precipitation of poststenotic myocardial ischemia was demonstrated in experimental studies and recently confirmed in patients with effort angina. Non-adrenergic, non-cholinergic neurotransmitters exist; however, their role in regulating coronary blood flow remains entirely unclear.     

The Influence of Somatostatin on Gallbladder Response to Intraduodenal Acid and Autonomic Nerve Stimulation in the Cat

The influence of somatostatin on the concentrating function and motility of the feline gallbladder has been studied with perfusion techniques in vivo. Somatostatin did not cause any change in the basal volume or concentrating function of the gallbladder. Duodenal acidification and also efferent electrical stimulation of the vagus nerves after atropinization reduced the net water absorption from the gallbladder, and these effects were blocked by intravenous somatostatin. The enhanced rate of net water absorption in response to electrical stimulation of the splanchnic nerves, however, was not influenced by somatostatin. Both the gastrointestinal peptides vasoactive intestinal peptide (VIP) and secretin reduce the net water absorption in the gallbladder. The blocking effect of the gallbladder's response to duodenal acid might be explained by an inhibition by somatostatin of secretin release from the duodenum. The inhibition of the gallbladder's reaction to vagal stimulation can be explained by a suppression of VIP release from noncholinergic, nonadrenergic nerve fibres in the gallbladder wall. Apart from the earlier described interference with gallbladder emptying, somatostatin seems to affect the regulation of the gallbladder's concentrating function. The results are discussed in view of the recent observation that patients with somatostatinoma characterized by high levels of circulating somatostatin usually have gallstone disease.     

糖尿病大鼠小肠肌间神经丛氮能神经的变化及其意义

目的探讨氮能神经在糖尿病大鼠小肠运动障碍中的作用。方法将50只大鼠随机分为正常对照组和槠尿病模型组,用链尿佐菌素建立大鼠糖尿病模型。3月后测定小肠传输速度,行小肠肌间神经丛氮能神经计数。结果糖尿病模型组大鼠小肠传输速度明显延迟,小肠肌间神经丛氮能神经细胞数和氮能神经神经节均明显减少。结论糖尿病小肠肌间神经丛氮能神经改变足导致小肠传输速率减慢的原因之一,从而引起小肠运动障碍。     

Perivascular Innervation: A Multiplicity of Roles in Vasomotor Control and Myoendothelial Signaling

The control of vascular resistance and tissue perfusion reflect coordinated changes in the diameter of feed arteries and the arteriolar networks they supply. Against a background of myogenic tone and metabolic demand, vasoactive signals originating from perivascular sympathetic and sensory nerves are integrated with endothelium‐derived signals to produce vasodilation or vasoconstriction. PVNs release adrenergic, cholinergic, peptidergic, purinergic, and nitrergic neurotransmitters that lead to SMC contraction or relaxation via their actions on SMCs, ECs, or other PVNs. ECs release autacoids that can have opposing actions on SMCs. Respective cell layers are connected directly to each other through GJs at discrete sites via MEJs projecting through holes in the IEL. Whereas studies of intercellular communication in the vascular wall have centered on endothelium‐derived signals that govern SMC relaxation, attention has increasingly focused on signaling from SMCs to ECs. Thus, via MEJs, neurotransmission from PVNs can evoke distinct responses from ECs subsequent to acting on SMCs. To integrate this emerging area of investigation in light of vasomotor control, the present review synthesizes current understanding of signaling events that originate within SMCs in response to perivascular neurotransmission in light of EC feedback. Although often ignored in studies of the resistance vasculature, PVNs are integral to blood flow control and can provide a physiological stimulus for myoendothelial communication. Greater understanding of these underlying signaling events and how they may be affected by aging and disease will provide new approaches for selective therapeutic interventions.     

刺五加离子导入治疗糖尿病周围神经病变30例疗效观察

为观察刺五加离子导入治疗糖尿病周围神经病变的临床疗效，用该法对31例糖尿病周围神经病变患者(治疗组)进行治疗，并与29例经常规糖尿病治疗者(对照组)进行对比。结果显示，治疗组各临床症状好转率，特别是肢体疼痛、足背动脉波动减弱、肢体皮肤色泽变浅及体位性低血压好转率明显高于对照组，两组比较有显著性差异(P＜0．01)；治疗组正中神经、尺神经和腓总神经的感觉神经传导速度(SCV)、运动末端潜伏期(MLP)较同组治疗前和对照组治疗后均明显改善，组间比较有显著性差异(P均＜0．01)。提示刺五加离子导入疗法可在一定程度上促进受损神经组织的修复和再生，改善神经髓鞘功能，降低糖尿病周围神经病变的致残率．     

The Efficacy of a Nerve Stimulator (Cavermap®) to Enhance Autonomic Nerve Identification and Confirm Nerve Preservation During Total Mesorectal Excision

PURPOSE Sexual dysfunction after total mesorectal excision may be caused by injury to the autonomic nerves. During surgery, nerve identification is not always achieved, and, to date, there has been no method to objectively confirm nerve preservation. The aim of this study was to assess the efficacy of a nerve-stimulating device (CaverMap?) to assist in the intraoperative identification of the autonomic nerves during total mesorectal excision, and objectively confirm nerve preservation after proctectomy is completed. PATIENTS AND METHODS Sexually active consecutive male patients undergoing total mesorectal excision were prospectively enrolled in this study. During pelvic dissection, the surgeon attempted to localize the hypogastric and cavernous nerves. Cavermap? was used to confirm these findings and to facilitate the identification in cases of uncertainty. At the completion of proctectomy, the nerves were restimulated to ensure preservation. Factors that could affect the surgeon’s ability to localize the nerves and Cavermap? to confirm this were evaluated. RESULTS Twenty-nine male patients with a median age of 58 years were enrolled in this study. An attempt to visualize the hypogastric nerves during dissection was made in 26 patients; the surgeon was able to identify the nerves in 19 (73 percent) patients. Cavermap? successfully identified the nerves in six of the seven remaining patients, and failed to identify them in only one case. An attempt to localize the cavernous nerves during dissection was made in 13 patients, of which localization was successful in 8 (61.5 percent) patients. Cavermap? improved the identification rate in four of the remaining five patients. After proctectomy, Cavermap? successfully confirmed the preservation of both hypogastric and cavernous nerves in 27 of 29 (93 percent) patients. A history of previous surgery statistically correlated with failure to identify the hypogastric nerves by the surgeon (P = 0.005). There were no adverse events related to use of the device. CONCLUSION Cavermap? may be a useful tool to facilitate identification of the pelvic autonomic nerves during total mesorectal excision and to objectively confirm nerve preservation. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, June 3 to 8, 2002, Chicago, Illinois. Poster presentation at the meeting of the Association of Coloproctology of Great Britain and Ireland, July 2 to 5, 2002, Manchester, United Kingdom. Podium presentation at the Tripartite Colorectal meeting, October 27 to 30, 2002, Melbourne, Australia. An erratum to this article is available at .     

Dis Colon Rectum, Vol. 47, No. 12, December 2004, pp. 2032–2038 (DOI: 10.1007/s10350-004-0718-5)

PURPOSE Sexual dysfunction after total mesorectal excision may be caused by injury to the autonomic nerves. During surgery, nerve identification is not always achieved, and, to date, there has been no method to objectively confirm nerve preservation. The aim of this study was to assess the efficacy of a nerve-stimulating device (CaverMap?) to assist in the intraoperative identification of the autonomic nerves during total mesorectal excision, and objectively confirm nerve preservation after proctectomy is completed. PATIENTS AND METHODS Sexually active consecutive male patients undergoing total mesorectal excision were prospectively enrolled in this study. During pelvic dissection, the surgeon attempted to localize the hypogastric and cavernous nerves. Cavermap? was used to confirm these findings and to facilitate the identification in cases of uncertainty. At the completion of proctectomy, the nerves were restimulated to ensure preservation. Factors that could affect the surgeons ability to localize the nerves and Cavermap? to confirm this were evaluated. RESULTS Twenty-nine male patients with a median age of 58 years were enrolled in this study. An attempt to visualize the hypogastric nerves during dissection was made in 26 patients; the surgeon was able to identify the nerves in 19 (73 percent) patients. Cavermap? successfully identified the nerves in six of the seven remaining patients, and failed to identify them in only one case. An attempt to localize the cavernous nerves during dissection was made in 13 patients, of which localization was successful in 8 (61.5 percent) patients. Cavermap? improved the identification rate in four of the remaining five patients. After proctectomy, Cavermap? successfully confirmed the preservation of both hypogastric and cavernous nerves in 27 of 29 (93 percent) patients. A history of previous surgery statistically correlated with failure to identify the hypogastric nerves by the surgeon (P = 0.005). There were no adverse events related to use of the device. CONCLUSION Cavermap? may be a useful tool to facilitate identification of the pelvic autonomic nerves during total mesorectal excision and to objectively confirm nerve preservation. Due to an electronic error in production, nine paragraphs of the Patients and Methods and Results section were omitted from the print and pdf versions of the article “The Efficacy of a Nerve Stimulator (Cavermap?) to Enhance Autonomic Nerve Identification and Confirm Nerve Preservation During Total Mesorectal Excision” by Giovanna M. da Silva, M.D., Oded Zmora, M.D., Lars B?rjesson, M.D., Nelly Mizhari, M.D., Norma Daniel, R.N., Farah Khandwala, M.S., Jonathan Efron, M.D., Eric G. Weiss, M.D., Juan J. Nogueras, M.D., Anthony M. Vernava III, M.D., Steven D. Wexner, M.D., published in the December 2004 issue of Diseases of the Colon & Rectum (Vol. 47, No. 12, pp 2032–2038, DOI ). The HTML version is correct. Below, the entire article is printed in its entirety with the omitted paragraphs in bold format. Springer regrets the error. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, June 3 to 8, 2002, Chicago, Illinois. Poster presentation at the meeting of the Association of Coloproctology of Great Britain and Ireland, July 2 to 5, 2002, Manchester, United Kingdom. Podium presentation at the Tripartite Colorectal meeting, October 27 to 30, 2002, Melbourne, Australia.