Muscular equivalent of the lower esophageal sphincter.

In order to measure muscle thickness and to define the muscular architecture at the gastroesophageal function, both en bloc fixation and a new method of preparing dried fiber specimens were used. Specimens were obtained from 32 kidney donors and human cadavers. Wall thickness was measured at 32 identical locations in the esophagus and stomach. The oblique gastroesophageal ring (GER) was the site of greatest muscular thickness and served as a reference point. From the GER the muscle thickness tapered (P less than 0.05 to P less than 0.001) in both a cephalic (esophageal) and caudal (gastric) direction for a length of 31 mm +/- 2.5 SD. The increase in thickness was due to an increase in the muscle mass (fiber aggregation) of the inner muscle coat. The muscle bundles of this coat split up 10.2 mm +/- 3.0 SD above the GER (fixed specimen) and for a length of 25 mm +/- 8 SD formed short transverse muscle clasps on the lesser curve side. Those muscle bundles on the greater curve side formed long oblique gastric fiber loops. The angle of His was inconstant in location and distal to the uppermost gastric oblique fibers (18 mm +/- 7 SD) and to the GER (9 mm +/- 6 SD).     

Identification of Diaphragmatic Crural Component of Gastroesophageal Barrier in the Rat

Manometric assessment of the diaphragmaticcontribution to the human gastroesophageal barrier isdifficult because it overlaps with that of the loweresophageal sphincter. Our aim was to investigate the barrier components in the rat in which thegastroesophageal junction is widely separated from thehiatus. Rats under anesthesia (N = 119) and after musclerelaxation (N = 14) underwent stationary andpull-through perfusion manometry. Inspiratorytransdiaphragmatic pressure gradient was 5.79 ±1.69 mm Hg and lower esophageal sphincter pressure was14.76 ± 8.63 mm Hg. A 13.78 ± 3.13-mmintraabdominal segment of the esophagus was interposed craniallybetween the sphincter and a group of phasic oscillationswith frequency identical to the respiratory rate andpressure of 13.81 ± 6.54 mm Hg, which disappeared after muscle relaxation. Both components of thegastroesophageal barrier in the rat are widely separatedby a long intraabdominal esophagus. This arrangementallows investigation of the behavior of both components under challengingconditions.     

Architecture and function of the gastroesophageal barrier in the piglet

We describe the anatomy and function of the gastroesophageal barrier in the piglet, Male piglets underwent dissection (N = 6) and gastroesophageal muscle layer histometry (N = 6). Sedated, nonintubated animals (N = 13) underwent four-probe perfusion esophageal manometry and the pressure profiles were related to the muscular thickness in the four quadrants. Hiatal and gastroesophageal anatomy are similar to our own. The muscle is thicker at the point where the clasp (on the right side) and sling fibers (on the left) concentrate. The pressure profiles were axially and radially asymmetric in coincidence with the thickness variations of the corresponding muscle layers. Sphincteric pressure was recorded as a plateau, whereas diaphragmatic crural pressure appeared as phasic oscillations in synchrony with respiration. The sphincter relaxed upon deglutition. In conclusion, the gastroesophageal structure and physiology are so similar in men and piglets that piglets are excellent models for research in this area.     

Cardiomyotomy in achalasia: which fibers do we cut?

Until now, it has not been quite clear which muscular fibers are cut when a cardiomyotomy for achalasia is carried out. In the present report, in a human achalasic gastroesophageal specimen, the mucosa of the stenotic segment was stripped off, allowing the fibers of the inner muscular coat to be seen. In addition, three cardiomyotomies at different sites were simulated. In achalasic specimens, the stenotic area is formed by the semicircular ('clasp') and oblique ('sling') muscular fibers. Different myotomies section these two muscular bands in distinct proportions. The stenotic segment in achalasia coincides topographically with the anatomic lower esophageal sphincter area. The site of cardiomyotomy is not irrelevant because this sphincter is not an annular muscle and the two muscular components of the sphincter can be sectioned in different ways. This may be important in post-operative results with regard to the relief of dysphagia and the appearance of gastroesophageal reflux.     

The role of left atrial muscular bundles in catheter ablation of atrial fibrillation.

OBJECTIVES: We sought to investigate the imaging of the left atrial (LA) muscular bundle and the relationship between the bundle and inducibility of tachyarrhythmia after pulmonary vein isolation (PVI). BACKGROUND: Noninducibility is used as a clinical end point of atrial substrate ablation after PVI. However, little is known about the role of the LA muscular bundles in tachyarrhythmia after PVI. METHODS: Forty-three consecutive patients with paroxysmal atrial fibrillation who underwent catheter ablation were included. Bi-atrial isochronal mapping was performed with the NavX system (St. Jude Medical Inc., St. Paul, Minnesota) during sinus rhythm. After 4 PVI, inducible organized LA flutter with or without transforming to atrial fibrillation (AF) (LA flutter/AF) was ablated with additional lines at the roof and/or mitral isthmus. RESULTS: The existence of bilateral muscular bundles was an independent predictor of LA flutter/AF after PVI (p = 0.02). Patients with LA flutter/AF after PVI had a greater index of the double potentials (5.4 +/- 3.4% vs. 2.8 +/- 1.8%, p = 0.006) and interpotential interval (33 +/- 5 ms vs. 29 +/- 4 ms, p = 0.02) than without LA flutter/AF. The muscular bundles were identified in 28% patients using 16-slice multidetector computed tomography, which were identical to the isochrone map. Patients with noninducible LA flutter/AF after PVI plus the additional linear ablation had a lower recurrence rate as compared with the patients without it (19% vs. 75%, p = 0.02). CONCLUSIONS: Left atrial muscular bundles may provide a conduction block line and barrier, which is important for the formation of LA flutter/AF after PVI. The noninducibility of LA flutter/AF achieved after additional linear ablation may contribute to a better outcome in RF ablation of paroxysmal atrial fibrillation.     

肠内营养对增龄大鼠肠黏膜上皮屏障的影响

目的 研究肠内营养（百普力）对老年大鼠增龄过程中肠黏膜上皮屏障变化的影响.方法 将20只12月龄和20只3月龄SD大鼠均随机分为肠内营养组和常规饮食组,肠内营养组给予常规饲料和肠内营养液（百普力）,常规饮食组给予标准饲料,饲养1月后取各组大鼠回肠组织常规HE染色观察形态学改变,半定量RT-PCR方法检测小肠黏膜组织中紧密连接蛋白（Occludin、ZO-1）mRNA表达水平,免疫组化法检测Occludin、ZO-1水平.统计学处理采用独立样本t检验和多元回归分析.结果 常规饮食组12月龄大鼠与3月龄大鼠相比：小肠绒毛高度降低（P＜0.05）,小肠黏膜组织中Occludin、ZO-1 mRNA表达减少（P＜0.05）,小肠黏膜组织中Occludin、ZO-1减少（P＜0.05）; 12月龄肠内营养组大鼠与常规饮食组大鼠相比,小肠黏膜厚度和绒毛高度增加（P＜0.05）,小肠黏膜组织中Occludin、ZO-1 mRNA表达增多（P＜0.05）,Occludin、ZO-1增多（P＜0.05）.结论 肠内营养（百普力）能改善老年SD大鼠肠黏膜上皮屏障中紧密连接蛋白（Occludin、ZO-1）的减少程度,对衰老时肠黏膜屏障损伤具有保护作用.     

Frequency of neuromuscular junctions on arteries of different dimensions in the rabbit, guinea pig and rat

The medio-adventitial border of a variety of perfusion-fixed arteries of young adult rabbits, guinea pigs and rats has been studied in the electron microscope. The arterial media in the different vessels ranged from 2 to 25 cells thick. Neuromuscular junctions, defined as axon varicosities containing synaptic vesicles closely apposed to the outer surface of smooth muscle cells, with only a single layer of basal lamina intervening between axon and muscle membranes, were identified in all three species. Junctions were found in most vessels less than 1 mm in diameter with a frequency ranging from 8,000-150,000 junctions per square millimeter of smooth muscle surface, the number generally increasing with decreasing arterial diameter. These small arteries were mostly, but not exclusively, muscular rather than elastic. In large arteries, such as abdominal aortae and some elastic arteries lying close to the heart (e.g. the carotid), no junctions were found. In a few vessels, such as guinea pig basilar (muscular) and rat and guinea pig superior mesenteric (elastic) arteries, junctions were found infrequently (1,000-4,000/mm2). The data indicate that all muscular arteries in rats and guinea pigs, and most muscular arteries in rabbits, receive innervation in the form of sympathetic neuromuscular junctions. Whilst a few elastic vessels are sparsely innervated with junctions, some are surrounded by axon bundles containing vesicle-filled varicosities. The physiological significance of the latter is obscure.     

Esophageal mucosal resistance. A factor in esophagitis

The development of esophageal damage depends on a number of factors. The components in the refluxate, including H+ ion, pepsin, bile salts, and pancreatic enzymes, are able to permeate the mucosa and cause injury. These agents may act individually or in combination. Balancing the effects of these damaging agents is the "esophageal mucosal barrier." This barrier is an integrated complex of anatomic and physiologic components that acts to maintain the integrity of the mucosa. Although the relative efficacy of the various components in developing an effective barrier is not understood completely, their physiologic and clinical importance in the face of "noxious" luminal contents remains critical. Understanding the interplay between the injurious agents in the refluxate and the esophageal mucosal barrier may allow for the development of new therapeutic measures in the treatment and prevention of gastroesophageal reflux disease.     

多种动物房室交界区形态结构种属差异的研究

为探讨多种动物房室交界区形态结构是否存在种属差异 ,本研究选用大白鼠、家兔、猪等动物房室交界区组织块作纵向平行及纵向垂直两个平面连续切片 ,观察多种动物房室交界区形态结构特征 ,探讨不同种动物房室交界区种属差异的可能性。结果 :①不同种属动物在有无形态不同的细胞束上有差异 ;②不同种属动物房室交界区细胞束的形态特征及其在房室交界区立体结构中的位置有差异 ;③不同种属动物的房室交界区后部形态结构及长度有差异 ;④不同种属动物房室交界区与心房肌连接部位及相连心房肌细胞形态有差异。结论 :不同种属动物房室交界区形态结构存在种属差异。     

冠状窦肌袖及其与左心房肌连接的解剖学研究

目的　观察冠状窦肌袖及其与左心房之间的肌性连接。方法　解剖 7个国人心脏标本 ,沿冠状窦长轴纵切 ,通过连续的大组织切片观察冠状窦肌袖及其与左心房之间的肌性连接。结果所有标本均可见形态与左房肌相同的肌袖 ,长度 2 1～ 35mm ,厚度 0 2～ 1 7mm。均见肌袖与左房肌之间的肌性连接。肌连接在大小部位上差异很大。有的仅有 1～ 2个大肌束 ;有的肌连接多而宽 ,和左房肌互相融合。同时观察到在冠状窦和左房肌之间的脂肪中可见许多小肌束。结论　围绕冠状窦有丰富的肌袖 ,其与左房间通过数目不等的肌纤维进行连接。冠状窦肌袖及其与左房间的肌连接构成了左右心房间传导通路的基质。     

Apoptosis in the muscular arteries from young spontaneously hypertensive rats.

OBJECTIVE: The purpose of this study was to test the hypothesis that a different incidence of apoptosis occurs in the mesenteric arteries of the spontaneously hypertensive rat (SHR) compared with its normotensive control the Wistar-Kyoto rat (WKY) at 1-2 weeks of age. DESIGN: We examined the incidence of apoptotic cells in the blood vessel wall of muscular arteries from the SHR and WKY at 1-2 weeks of age using two techniques of apoptosis measurement DNA laddering and 3'-OH end labelling. We also measured the volume of the blood vessel wall components and lumen sizes with the confocal microscope to determine whether a differential incidence of apoptosis occurred between the two rat strains. METHODS: We used phenol/chloroform extraction to isolate genomic DNA and assess DNA fragmentation, with gel electrophoresis to determine DNA laddering, and 3'-OH end labelling, where the enzyme terminal deoxynucleotidyl transferase catalyses the addition of fluorescein-conjugated nucleotides to the cut ends of DNA, to detect in situ DNA fragmentation. The volume per unit length of the blood vessel structural components was measured by optical sectioning with the confocal microscope. RESULTS: We found that the SHR had a significantly decreased incidence of cellular apoptosis over WKY. This was true for both the electrophoretic method where SHR had significantly less fragmented DNA (molecular size < 600 bp) than WKY (P= 0.01), and for the microscopic method where SHR had fewer labelled cells in both the adventitia (P= 0.01) and the media (P= 0.0001) layers of large mesenteric arteries. The volumes of the adventitia, media and lumen in the large mesenteric arteries were similar between the two strains at this age. CONCLUSION: These findings suggest that a differential incidence of cellular apoptosis at the age of 1 -2 weeks may be responsible for the larger media volume found in older SHR and thus contributes to the development of hypertension in these animals.     

Effect of prolonged physical exercise on muscular phospholipase A2 activity in rats

Prolonged muscular exercise stimulates glucose uptake by the working muscles themselves. The mechanism of this phenomenon is at present unclear. It has been proposed that the kallikrein-kinin-prostaglandin system plays a role in the physiological regulation of muscular glucose metabolism during exercise. Since bradykinin can stimulate phospholipase A2, a key enzymatic step in prostaglandin synthesis, phospholipase A2 activity was assayed in rats at rest and in rats compelled to swim for 60 minutes. The physiological significance of an increase in muscular phospholipase A2 activity is not clear. Since bradykinin can stimulate both muscular glucose uptake and phospholipase A2 activity, it is possible that the increased activity of this enzyme is involved in the exercise-induced increase of muscular glucose uptake. Phospholipase A2 activity was strongly increased in the exercising rat muscles. A small but significant increase in phospholipase A2 activity was observed in the heart, whereas no variation in activity was demonstrated in either the kidney or the liver of exercising rats. These findings strongly indicate that prolonged exercise increases muscular phospholipase A2 activity only in the muscle and heart. This phenomenon appears to be strongly related to muscular contraction, since other stress situations such as cold exposure did not modify phospholipase A2 activity. Our data are in agreement with the hypothesis of a possible involvement of prostaglandins in the priming action of insulin on glucose uptake during muscular work.     

Perimeter and Location of the Muscular Gastroesophageal Junction or ‘Cardia’ in Control Subjects and in Patients with Reflux Esophagitis or Achalasia

The location and perimeter of the true muscular gastroesophageal junction or cardia were determined during operation in 6 patients with achalasia, in 20 control subjects, and in 40 patients with reflux esophagitis. These two latter groups were submitted to highly selective vagotomy, owing to duodenal ulcer in the control subjects and as part of the surgical technique in reflux esophagitis patients. The careful dissection and isolation of the distal 5–6 cm of the esophagus and esophagogastric junction permitted us to measure the location and perimeter very precisely. There was a very close correlation between the distance incisors-beginning of gastroesophageal sphincter measured preoperatively and the distance incisors-cardia measured during surgery. The cardia could be clearly identified by external inspection corresponding to the limit between the longitudinal muscle layer of the esophagus and the serosal surface of the stomach. The perimeter of the cardia in the patients with reflux esophagitis was significantly larger than the perimeter of the control subjects (p<0.001). Intraoperative manometry demonstrated that the external limit of the cardia corresponded to the beginning of the gastroesophageal sphincter. Patients with achalasia had significantly smaller perimeter than controls or reflux esophagitis patients (p < 0.001).     

Elimination of cavotricuspid isthmus conduction by a single ablation lesion: observations from a maximum voltage-guided ablation technique.

AIMS: The architecture of the cavotricuspid isthmus has been shown to be highly variable made of a large number of interspersed bundles in the majority. Targeting high-amplitude signals has resulted in short-ablation times, likely due to the selective ablation of such bundles. We report a series of cases where a single site ablation resulted in bidirectional block, supporting the hypothesis that conduction can occur over a discrete portion of the isthmus. METHODS AND RESULTS: Sixty consecutive patients underwent ablation for isthmus-dependent atrial flutter using voltage-guided approach between September 2005 and June 2006. We found in five patients (8.3%) (four male, mean age 58.1 +/- 11.4 years), in whom bidirectional block was achieved by ablation at a single site. The isthmus was mapped at the 6 o'clock LAO position, and bipolar amplitude was measured during pull-back to find the site of largest atrial voltage. The atrial and ventricular electrogram (EGM) measured 2.00 +/- 1.6 and 0.2 +/- 0.1 mV, respectively, at the successful site, resulting in the mean atrium/ventricle ratio of 9.1 +/- 4.1. The total radiofrequency time was 83.8 +/- 25.3 s, and the procedure time was 68.6 +/- 10.4 min, including 30 min waiting time after the procedure. Flutter has not recurred over 5.7 +/- 4.0 months follow-up. CONCLUSION: Targeting the largest atrial EGM in the isthmus can produce bidirectional block with a single site ablation. This supports the hypothesis that trans-isthmus conduction can occur over a discrete part of the isthmus, likely due to the underlying bundle architecture.     

Right atrial flutter isthmus revisited: normal anatomy favors nonuniform anisotropic conduction

INTRODUCTION: The "flutter isthmus," the part of the lower right atrium between the eustachian valve and the tricuspid annulus inferior to the coronary sinus os, is considered the crucial zone for conduction delay necessary for the genesis of atrial flutter. However, the underlying mechanism remains unclear. METHODS AND RESULTS: We studied the "flutter isthmus" in 50 hearts obtained at autopsy from patients without atrial tachyarrhythmias. The muscular trabecular arrangement was dissected carefully by peeling off the endocardium. Documentation of the trabecular arrangement focused, in particular, on the question of whether there was a uniform pattern of well-aligned muscle trabeculae or a nonuniform architecture. It appeared that a nonuniform trabecular pattern prevailed (37/50 [74%]). In these hearts, the muscular arrangement showed abundant cross-overs and interlacing trabeculae, particularly in the zone immediately inferior to the coronary sinus os. Connections also occurred along the inferior rim of the os. CONCLUSION: The normal anatomy of the lower right atrium favors nonuniform muscular trabeculation, with interlacing bundles and a multitude of cross-overs. The potential for conduction delay is present in the vast majority of normal hearts. This raises the question as to what has changed in the hearts of patients with atrial flutter such that the potential for conduction delay and reentry has become effective.     

The contribution of the diaphragm and an intrinsic sphincter to the gastroesophageal antireflux barrier. An experimental study in the dog

The components of the mechanical gastroesophageal antireflux barrier were studied in anesthetized dogs (15-18.5 kg). Pressure in the gastroesophageal junction area was recorded by pull-through manometry (using an infused end-hole-provided catheter) during gastric filling (distension) with water. In addition, the gastric volume at which reflux occurred was used as a measure of function and competence. Each dog was studied while intact and spontaneously breathing, after muscle relaxation, after excision of the left half of the diaphragm, and after death. In the intact dogs a barrier with a mean resting pressure of 20 (range, 14-26) cm H2O was recorded. During gastric filling the barrier pressure initially increased to 32 (16-42) cm H2O before steadily decreasing until reflux occurred. The highest pressure was recorded with 625 ml (250-1500 ml) in the stomach. Reflux occurred at a gastric volume of 3200 ml (2300-4000 ml). Muscle relaxation changed neither resting pressure nor reflux volume significantly. After excision of the left half of the diaphragm a barrier with a resting pressure of 15 (6-22) cm H2O was still recorded. Reflux then occurred at a gastric volume of 1400 ml (500-2500 ml). In dead dogs no pressure barrier could be recorded, and reflux was provoked already by 500 ml (250-750 ml) in the stomach. The presence of a mechanical barrier also after excision of the left half of the diaphragm, as evidenced by both pressure and reflux volume, can only be explained by an intrinsic sphincter, a lower esophageal sphincter (LES). However, the experiments also showed that the diaphragm contributed to the competence of the LES. This contribution was at first passive.     

A Rat Surgical Model of Esophageal Metaplasia and Adenocarcinoma-Induced by Mixed Reflux of Gastric Acid and Duodenal Contents

Recent clinical data have revealed that mixed reflux (MR) of gastric acid and duodenal contents frequently occurs in patients with gastroesophageal reflux disease and a progressive increase of MR occurs with increasing severity across gastroesophageal reflux disease. Herein we report a novel rat surgical model in which esophageal metaplasia and adenocarcinoma develop as complications of MR. The model was created by performing an esophagojejunostomy and a gastrojejunostomy 5 mm proximal to the esophagojejunal anastomosis in 40 rats. Severe inflammatory and proliferative changes, high prevalence of esophageal metaplasia (78%), and adenocarcinoma (50%) were observed in the lower part of the esophagus of rats 20 weeks after surgery. The resulting esophageal lesions resembled those described in humans and supported a progression from intestinal metaplasia to dysplasia and, ultimately, esophageal adenocarcinoma. Such a model may provide a useful tool in study of human reflux-induced carcinogenesis.     

Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats

BACKGROUND AND AIMS: In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats. METHODS: In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor alpha (TNF-alpha), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells. RESULTS: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-alpha expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes. CONCLUSIONS: IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.