人食管下括约肌G蛋白耦联受体的表达及作用机制

人食管下括约肌(LES)包括神经调节、自身调节、体液调节三种调节方式。三种方式中体液调节涉及多种激素类物质,但均与G蛋白耦联受体结合发挥作用。激素类物质因配体和受体的不同调节功能也不尽相同。通过研究其作用机制发现通过进一步开发,有望通过药物调节治疗食管动力性疾病。     

几种全身麻醉对小儿下食管括约肌的影响

下食管括约肌是防止胃内容反流的重要屏障。本文通过对52例小儿胃食管压力的测定,观察了几种全麻过程中药物对小儿下食管括约肌的影响。结果表明:乙醚使屏障压(下食管括约压与胃压之差,BrP)先升后降,50min后差异具有统计学意义,70min时比对照下降约1.60kPa(12mmHg)。普鲁卡因静复液麻醉对下食管括约肌的影响比乙醚轻,BrP呈缓慢下降趋势。羟丁酸钠和氯胺酮对BrP无明显影响,不增加反流发生的可能性。但麻醉手术中反流发生的机制比较复杂,尚待进一步阐明。日前,减少胃内容和保护好呼吸道仍非常必要。     

血管活性肠肽介导人食管下括约肌舒张的实验研究

目的研究血管活性肠肽(VIP)对人食管下括约肌(LES)套索纤维和钩状纤维的作用及其差异,探索VIP是否属于非肾上腺非胆碱能(NANC)神经递质。方法选取2010年3～8月在河北医科大学第四医院因高位食管中段癌行食管大部切除术患者30例,其中男14例,女16例;年龄(58.0±6.1)岁。选LES标本,分离钩状纤维和套索纤维,做外源性VIP对套索纤维和钩状纤维的浓度效应曲线,比较分别在电场刺激(EFS)和外源性VIP作用下,VIP(10-28)对LES的不同影响。结果在LES离体实验条件下,外源性VIP在不同浓度下可使套索纤维和钩状纤维产生浓度依赖性舒张反应,在相同VIP浓度下套索纤维和钩状纤维舒张变化的差异有统计学意义(P<0.05),套索纤维的舒张作用大于钩状纤维。VIP(10-28)能够短暂一过性抑制外源性VIP的作用。VIP(10-28)对EFS作用后的套索纤维和钩状纤维均产生了短暂一过性的抑制作用。结论 EFS诱导钩状纤维和套索纤维的舒张与VIP有关,实验结果支持VIP是人LES内NANC神经递质之一。     

胃食管反流病患者伴有或不伴有食管黏膜损伤与食管上、下括约肌压力相关性研究

目的研究伴或不伴食管黏膜损伤的胃食管反流病（gastroesophageal reflux disease,GERD）患者在食管动力方面的差异。 方法回顾性分析2015年1月至2017年12月,解放军总医院就诊的有反酸、烧心、胸痛等症状的患者,24 h食管pH监测Demeester积分≥14.72分,根据内镜检查结果分为糜烂性反流病（ERD）组和非糜烂性反流病（NERD）组,比较2组患者食管动力学指标的变化。 结果NERD组与ERD组UESP平均值数值相似,差异无统计学意义（P=0.168）。其余指标UESRP平均值、LESP最小值、LESP平均值、LESRP平均值、LESRP最大值、DCI中NERD组均高于ERD组,差异均有统计学意义（P<0.001）。NERD组平均年龄明显小于ERD组,差异有统计学意义（P<0.000 1）。NERD组患者身高较ERD组偏低,体重较轻,身体质量指数（body mass index,BMI）也较小,差异有统计学意义（P<0.000 1）。 结论随着年龄的增大或BMI的增加,可能增加GERD患者食管黏膜损伤的风险。此外,糜烂性反流病患者较非糜烂性反流病的上、下食管括约肌动力障碍更严重。     

七氟醚对小儿食管下段括约肌功能的影响

目的　观察七氟醚麻醉对小儿食管下段括约肌 (LES)功能的影响。方法　 15例行择期手术小儿 ,年龄 3～ 7岁 ,ASAⅠ～Ⅱ级 ,术前无胃食管反流症状 ,亦未用术前药。静脉注射γ 羟基丁酸钠和阿曲库铵诱导插管后 ,吸入七氟醚维持麻醉。吸入前及吸入浓度分别达 0 5、1 0和1 5MAC时 ,用PaPolygrafHR胃肠动力监测系统进行测压。用专业软件处理、储存下列数据 :LES压力 (LESP)、胃压 (GP)、屏障压 (BrP)、长度 (SL)、压力向量容积 (PVV)。结果　随七氟醚MAC的升高 ,LESP、BrP和PVV均有所下降 ,与基础值相比 ,0 5MAC和 1 0MAC时差异无显著意义 (P >0 0 5 ) ;1 5MAC时差异有显著性意义 (P <0 0 5 )。而SL和GP无明显变化。结论　七氟醚对小儿LES功能的影响较小 ,有利于维持其功能稳定。但有高度反流危险的小儿 ,应避免使用高浓度七氟醚     

一氧化氮在胆囊收缩素调节犬Oddi括约肌舒张通路中的作用

目的 探讨一氧化氮(NO)在胆囊收缩素(CCK)调节犬Oddi括约肌(SO)舒张的通路中发挥的作用.方法 打开犬十二指肠后逆行插入测压管至胆总管及SO,测定SO压力及CCK与NO对其产生的影响.结果 NO与生理剂量(20ng/kg)CCK合用后舒张SO的效应,相比单独注射CCK增强,却与单独使用NO无异;而与药理剂量(100 ng/kg)CCK合用后,相对降低了SO的运动性,但不能改变其快速兴奋SO的趋势.结论 CCK存在着兴奋和抑制SO的两种作用途径,而NO作为一种非肾上素腺能非胆碱能神经(NANC)的递质,可能在CCK的舒张通路中起到了重要作用.     

地氟醚与安氟醚对小儿食管下段括约肌功能的影响

目的观察地氟醚与安氟醚麻醉对小儿食管下段括约肌(LES)功能的影响.方法26例行择期手术小儿,年龄3～7岁,ASAⅠ～Ⅱ级,术前无胃食管反流症状,亦未用术前药.静脉注射羟丁酸钠和阿曲库铵诱导插管后,随机分为地氟醚(D组)和安氟醚(E组)两组.在吸入地氟醚与安氟醚前以及当其吸入浓度分别达到0.5MAC、1.0MAC、1.5MAC时,用PaPolygraf HR胃肠动力监测系统测定下列数据LES压力(LESP)、胃压(GP)、屏障压(BrP)、长度(SL)、压力向量容积(PVV)和向量容积的三维立体图象.结果随地氟醚或安氟醚MAC的升高,D组各项指标与吸入前相比无明显变化(P＞0.05);而E组的LESP、BrP和PVV则呈进行性下降,与其基础值相比差异显著(＜0.01),并且也低于相同MAC的D组相应各值(＜0.01).结论地氟醚对小儿LES功能无明显影响而安氟醚对其影响较大,故有高度反流危险的小儿,以选用地氟醚维持麻醉更为安全.     

胆囊收缩素受体对人食管下括约肌套索纤维和钩状纤维的调节机制

目的探讨人食管下括约肌的套索纤维和钩状纤维对CCK-8和胃泌素-17的反应特点,以及胆囊收缩素受体对两者的调节作用。方法运用离体组织张力测量技术,得出套素纤维和钩状纤维对CCK-8和胃泌素-17的最大收缩效应值(Emax),以及特异性胆囊收缩素受体拮抗剂对 CCK-8的pKB值。结果套索纤维对CCK-8和胃泌素-17产生了较强的浓度依赖性收缩反应 [Emax值:(5．18±0．50)mN／mm2和(4．91±0．95)mN／mm2],而钩状纤维的收缩强度[Emax值: (0．73±0．23)mN／mm2和(0．72±0．14)mN／mm2]显著低于套索纤维(P<0．001;P<0．01)。 CR1409和CR2945对CCK-8引发的套索纤维收缩均产生了浓度依赖性抑制作用,前者的pKB值 (7．51±0．11)大于后者(7．15±0．11)(P<0．05)。结论套索纤维对CCK-8和胃泌素-17刺激的收缩强度显著大于钩状纤维,CCKA受体在其中发挥着更为重要的作用。     

Long-term retention of endoscopically placed hydrogel prostheses at the lower esophageal sphincter in pigs

Background: Using flexible endoscopic methods, hydrogel prostheses can be safely placed, retained for long periods of time, and removed from the esophageal submucosa of pigs. This new technique may have future applications in the treatment of gastroesophageal reflux disease in selected situations. Methods: In a controlled, prospective trial, farm pigs (n = 28) or Sinclair mini-swine (n = 18) underwent sequential placements of 2–13 pliable, radio-opaque hydrogel prostheses into the submucosa of the esophagus during a single endoscopy session. A novel endoscope-overtube device was used. Followup endoscopy and/or fluoroscopy sessions were video-recorded at 6-week, 12-week, 6-month, and yearly intervals. The endoscopic removal of hydrogels was tested in vivo. Necropsy specimens were inspected for signs of chronic inflammation. Results: Overall, 98% of delivery attempts were successful (288/293). Only three hydrogels were lost after 6 weeks. Short-term animals (n = 36) retained 88% of hydrogels for periods up to 6 months. Intact hydrogels (n = 12) were easily removed from four animals at endoscopy. Long-term subjects had two or three hydrogels per animal, using either a beveled-needle device (six pigs) or a trocar design (four pigs). Trocar design: nine of nine prostheses retained at 3 years (100%). Needle design: nine of 10 prostheses retained at 3 years (90%). No significant adverse event occurred. Growth curves were similar between groups. All hydrogels remained pliable to gross inspection upon in vivo removal or necropsy. Pathology showed minimal fibrosis and no chronic inflammation. Conclusions: A novel endoscopic overtube device allows for the successful delivery of multiple hydrogel prostheses with acceptable safety and long term retention rates. These hydrogel prostheses can also be easily removed from the submucosal space of the esophagus.     

Response of the lower esophageal sphincter to gastric distention by carbonated beverages

Gastroesophageal reflux disease often occurs in patients with normal resting pressure and length of the lower esophageal sphincter. Such patients often have postprandial reflux. The mechanism of postprandial reflux remains controversial. To further clarify this, we studied the effect of carbonated beverages on the resting parameters of the lower esophageal sphincter. Nine asymptomatic healthy volunteers underwent lower esophageal sphincter manometry using a slow motorized pull through technique after ingestion of tap water and carbonated beverages. Resting pressure, overall length, and abdominal length of the lower esophageal sphincter were measured. All carbonated beverages produced sustained (20 minutes) reduction of 30–50% in all three parameters of the lower esophageal sphincter. In 62%, the reduction was of sufficient magnitude to cause the lower esophageal sphincter to reach a level normally diagnostic of incompetence. Tap water caused no reduction in sphincter parameters. Carbonated beverages, but not tap water, reduce the strength of the lower esophageal sphincter. This may be relevant to the pathogenesis of gastroesophageal reflux disease, especially in Western society.     

Effects of sevoflurane and enflurane on lower esophageal sphincter pressure and gastroesophageal pressure gradient in children

Purpose. The effects of sevoflurane and enflurane on the intraluminal pressure of the lower esophagus (LE), lower esophageal sphincter (LES), and stomach were investigated in paralyzed and mechanically ventilated children under general anesthesia. Methods. A total of 14 children, ASA physical status class I without risk factors for regurgitation, scheduled for orthopedic surgery were studied. After induction of anesthesia, we inserted a gastrointestinal pressure sensor nasally and monitored the intraluminal pressure of the LE, LES, and stomach under various concentrations of sevoflurane or enflurane with 66% nitrous oxide in oxygen prior to surgical incision. The barrier pressure (BrP), which is the difference between LES pressure and intragastric pressure, was calculated. Results. Sevoflurane at 2.0 and 2.5 minimum alveolar concentration (MAC) decreased LES pressure, and enflurane at 2.0 and 2.5 MAC decreased both LES pressure and BrP in anesthetized children. The intraluminal pressure of the LE and stomach were not altered in either group. Conclusion. Sevoflurane and enflurane have an inhibitory effect on LES smooth muscle in anesthetized children. However, since the reduction was relatively low, even at high concentrations, these inhalation anesthetics are unlikely to influence gastroesophageal reflux during anesthesia. Received for publication on April 16, 1998; accepted on July 21, 1998     

The effect of hydrocephalus on lower esophageal sphincter smooth muscle reactivity: experimental study

Purpose

The aim of this study was to assess the pharmacophysiological significance of the enteric nervous system for the mechanical responses of lower esophageal sphincter (LES) in infantile rats with kaolin-induced hydrocephalus.

Material and methods

Hydrocephalus was created in 7-day-old rats by injection of kaolin into the cisterna magna. After 10 days, rats were decapitated. Contractile (KCl, carbachol) and relaxant (isoprenaline, papaverine) responses were determined by using in vitro muscle technique in isolated LES smooth muscle strips.

Results

The receptor-mediated contractile and relaxant response to carbachol and isoprenaline in the LES smooth muscle was impaired in rats with hydrocephalus. There was no significant difference in the KCl and papaverine response in hydrocephalic and sham operated rats.

Conclusion

Our findings suggest that hydrocephalus may impair receptor-mediated contractile and relaxant activity of LES smooth muscle leading to gastroesophageal reflux.     

Surgical management of hypertensive lower esophageal sphincter with dysphagia or chest pain

Hypertensive lower esophageal sphincter (LES) is an uncommon manometric abnormality found in patients with dysphagia and chest pain, and is sometimes associated with gastroesophageal reflux disease (GERD). Preventing reflux by performing a fundoplication raises concerns about inducing or increasing dysphagia. The role of myotomy in isolated hypertensive LES is also unclear. The aim of this study was to determine the outcome of surgical therapy for isolated hypertensive LES and for hypertensive LES associated with GERD. Sixteen patients (5 males and 11 females), ranging in age from 39 to 89 years, with hypertensive LES (>26 mm Hg; i.e., >95th percentile of our control population) who had surgical therapy between 1996 and 1999 were reviewed. Patients with a diagnosis of achalasia and diffuse esophageal spasm were excluded. All patients had dysphagia or chest pain. Eight of 16 patients had symptoms of GERD, four had a type III hiatal hernia, and four had isolated hypertensive LES pain. Patients with hypertensive LES and GERD or type III hiatal hernia had a Nissen fundoplication, and those with isolated hypertensive LES had a myotomy of the LES with partial fundoplication. Outcome was assessed as follows: excellent if the patient was asymptomatic; good if symptoms were present but no treatment was required; fair if symptoms were present and required treatment; and poor if symptoms were unimproved or worsened. All patients were contacted by telephone for symptom assessment at a median of 3.6 years (range 3 to 6.1 years) after surgery. Patients with hypertensive LES and GERD or type III hiatal hernia had significantly lower LES pressure than those with isolated hypertensive LES (29.9 vs. 47.4 mm Hg; P = 0.013). Dysphagia and chest pain were relieved in all patients at long-term follow up. Outcome was excellent in 10 of 16, good in 3 of 16, and fair in 3 of 16. All patients but one were satisfied with their outcome. Patients with hypertensive LES are a heterogeneous group in regard to symptoms and etiology. Treatment of patients with hypertensive LES should be individualized. A Nissen fundoplication for hypertensive LES with GERD or type III hiatal hernia relieves dysphagia and chest pain suggesting reflux as an etiology. A myotomy with partial fundoplication for isolated hypertensive LES relieves dysphagia and chest pain suggesting a primary sphincter dysfunction. Presented at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida, May 17–22, 2003.     

Tailored augmentation of the lower esophageal sphincter in experimental antireflux operations

Background: Modern upper GI function studies allow for the detection of several pathophysiological factors that contribute to gastroesophageal reflux disease. The information obtained can lead to therapeutic consequences in patients with an indication for a surgical intervention, i.e., an individualized choice of antireflux procedure according to the existing pathophysiologic defect. Methods: In an experimental study on mini-pigs the mechanical effect of four standardized antireflux operations (anterior and posterior 180° hemifundoplication, Nissen-DeMeester and Nissen-Rossetti 360° fundoplication) on the lower esophageal sphincter (LES) was investigated. It was the aim of the study to objectively determine the extent of changes in pressure and length parameters at the LES according to the performed antireflux procedure. Results: It could be demonstrated that different degrees of fundic wrap formation lead to a proportional mechanical effect at the LES according to the size of this wrap. Conclusion: Choosing a distinct type of fundoplication will allow for a tailored augmentation of the LES according to the individual functional defect. Received: 29 January 1997/Accepted: 2 April 1997     

The effects on the lower esophageal sphincter of sevoflurane induction and increased intra-abdominal pressure during laparoscopy

BACKGROUND: Today sevoflurane is one of the most frequently used volatile anesthetics. The speed of induction can approach that of intravenous anesthetics, and case reports using sevoflurane induction for emergency anesthesia have been published. The purpose of this study in laparoscopic cholecystectomy patients was to investigate the effects of sevoflurane during inhalation induction on the lower esophageal sphincter pressure (LESP) and barrier pressure (BrP). The effects on lower esophageal sphincter (LES) and BrP of increased intra-abdominal pressure during laparoscopy were also evaluated. METHODS: We recorded LESP and BrP in nine patients using a Dent sleeve device. Recordings were made before and after inhalation induction of anesthesia with 8% sevoflurane, as well as before and after insufflation of CO(2) into the abdomen. RESULTS: After induction with sevoflurane, LESP (P= 0.039) and BrP (P= 0.020) decreased. Nevertheless, BrP was kept positive in all patients. Insufflation of CO(2) into the abdomen during laparoscopy induced a significant increase in LESP (P= 0.02) and gastric pressure (P= 0.004). However, there was no significant change in BrP (P= 0.66); it increased in four patients and decreased in five. CONCLUSION: BrP was kept positive in all patients after induction of anesthesia. Therefore, we believe that in combination with cricoid pressure, inhalation induction with sevoflurane might be a safe choice. As the adaptive increase in LESP during laparoscopy was not enough to retain a barrier pressure in all patients, it is important to be aware of the risk of regurgitation throughout the anesthesia.