Proximal gastric vagotomy: does it have a place in the future management of peptic ulcer?

PubMed

Johnson, A G

2000-03-01

Proximal gastric vagotomy (PGV) is a modification of truncal vagotomy, which was introduced by Dragstedt for the treatment of duodenal ulcer (DU) in 1943. It is a technically demanding operation; but when performed by an experienced surgeon, it is safe and gives a cure rate for DU of more than 90%, with minimal side effects. The operation permanently alters the natural history of the disease and may be used for gastric ulcer (GU), with ulcer excision; but it is not as effective. Further adaptations, such as posterior truncal vagotomy with anterior seromyotomy, were introduced to simplify and shorten the operation, but they did not receive wide acceptance. Recently, with the identification of Helicobacter, it was found that DU can also be cured by eliminating the infection. PGV is therefore used electively in patients with persistent DU that is not Helicobacter-positive or in the few in whom Helicobacter cannot be eliminated. In patients with bleeding or perforated DUs, PGV may be used in conjunction with underrunning the vessel or patching the perforation. However, few surgeons doing emergency peptic ulcer surgery have experience with PGV, so simple suture followed by medical treatment is the safest option. Because elective PGV is now a rare procedure, patients should be referred to a center with special expertise. If Helicobacter becomes resistant to antibiotics in the future, surgery may be needed regularly again, but the technical nuances would have to be learned.

Association of Vagotomy and Decreased Risk of Subsequent Ischemic Stroke in Complicated Peptic Ulcer Patients: an Asian Population Study.

PubMed

Fang, Chu-Wen; Tseng, Chun-Hung; Wu, Shih-Chi; Chen, William Tzu-Liang; Muo, Chih-Hsin

2017-12-01

The primary management of peptic ulcers is medical treatment. Persistent exacerbation of a peptic ulcer may lead to complications (perforation and/or bleeding). There has been a trend toward the use of a less invasive surgical simple suture, simple local suture or non-operative (endoscopic/angiography) hemostasis rather than acid-reducing vagotomy (i.e., vagus nerve severance) for treating complicated peptic ulcers. Other studies have shown the relationship between high vagus nerve activity and survival in cancer patients via reduced levels of inflammation, indicating the essential role of the vagus nerve. We were interested in the role of the vagus nerve and attempted to assess the long-term systemic effects after vagus nerve severance. Complicated peptic ulcer patients who underwent truncal vagotomy may represent an appropriate study population for investigating the association between vagus nerve severance and long-term effects. Therefore, we assessed the risks of subsequent ischemic stroke using different treatment methods in complicated peptic ulcer patients who underwent simple suture/hemostasis or truncal vagotomy/pyloroplasty. We selected 299,742 peptic ulcer patients without a history of stroke and Helicobacter pylori infection and an additional 299,742 matched controls without ulcer, stroke, and Helicobacter pylori infection from the National Health Insurance database. The controls were frequency matched for age, gender, Charlson comorbidity index (CCI) score, hypertension, hyperlipidemia history, and index year. Then, we measured the incidence of overall ischemic stroke in the two cohorts. The hazard ratio (HR) and the 95% confidence intervals (CIs) were estimated by Cox proportional hazard regression. Compared to the controls, peptic ulcer patients had a 1.86-fold higher risk of ischemic stroke. There were similar results in gender, age, CCI, hypertension, and hyperlipidemia stratified analyses. In complicated peptic ulcer patients, those who received

Effect of proximal vagotomy and Roux-en-Y diversion on gastric emptying kinetics in asymptomatic patients.

PubMed

Urbain, J L; Penninckx, F; Siegel, J A; Vandenborre, P; Van Cutsem, E; Vandenmaegdenbergh, V; De Roo, M

1990-10-01

The role of the distal stomach in gastric emptying was studied. Ten patients with proximal gastric vagotomy (PV) and 10 age-matched patients with Roux-en-Y gastro-jejunostomy (R-Y) were compared with 10 healthy controls. Gastric emptying of solids and liquids was determined by the use of Tc-99m SC scrambled eggs and In-111 DTPA. In PV, gastric emptying of both solids and liquids was delayed; the prolongation with solids was mainly accounted for by an abnormal lag phase. In R-Y patients, no lag phase was observed, and the solid emptying curve pattern was characterized by early rapid emptying followed by very slow emptying. Both the solid and liquid phases were prolonged. The lag phase is affected by proximal vagotomy and is mainly determined by the distal stomach, which appears to be essential for normal emptying.

Effect of vagotomy and vagal cooling on bronchoconstrictor response to substance P in sheep.

PubMed

Corcoran, B M; Haigh, A L

1995-10-01

The bronchoconstrictor effect of intravenous substance P can be antagonised by atropine pre-treatment in several species, and we have previously reported this finding in anaesthetised sheep. In the present study, we have assessed the effect of cooling the right vagus after sectioning the left vagus (n = 6), and bilateral vagotomy (n = 7) on the bronchoconstrictor response to a single intravenous dose of substance P (SP) (0.3-1.0 mumol/kg) in anaesthetized female sheep aged 6 to 12 months. Respiratory parameters including tidal volume, flow and transpulmonary pressure pressure were measured, from which pulmonary resistance (RL; cmH2O.1(-1).s) and dynamic compliance (CDyn; ml.cmH2O(-1) were calculated. Systemic arterial pressures were also measured. Vagal cooling significantly attenuated the bronchoconstrictor response to SP at 7 degrees C (RL P < 0.01; Cdyn P < 0.001). A further reduction in the response to SP occurred at 3 degrees C, but this was not statistically significantly different from the response at 7 degrees C. Vagotomy abolished the response to SP. SP caused mild, but statistically insignificant, hypotension (119.7 vs. 107.7 mmHg). These results suggest SP causes bronchoconstriction in the anaesthetised sheep by vagal reflex mechanisms, involving stimulation of myelinated nerve fibre endings.

The effect of vagotomy and drainage on the small bowel flora

PubMed Central

Browning, G. G.; Buchan, K. A.; Mackay, C.

1974-01-01

The incidence of small intestinal colonization in unoperated duodenal ulcer patients was low and similar to that in the normal population. The majority of patients seven to 10 days following truncal vagotomy and drainage were colonized whereas none of a control group of patients following simple closure of a perforated duodenal ulcer was colonized. In patients with pyloroplasty, this high incidence fell to control levels on average 18 months postoperatively, but in patients with a gastro-jejunostomy, the incidence remained raised probably due to the presence of the afferent loop. Only two patients developed episodic diarrhoea and there was no obvious association with small bowel colonization. PMID:4820640

Bilateral vagotomy inhibits apnea and attenuates other physiological responses after blunt chest trauma.

PubMed

Gryth, Dan; Rocksén, David; Arborelius, Ulf P; Drobin, Dan; Persson, Jonas K E; Sondén, Anders; Bursell, Jenny; Olsson, Lars-Gunnar; Kjellström, B Thomas

2008-06-01

Behind armor blunt trauma (BABT) is defined as the nonpenetrating injury resulting from a ballistic impact on body armor. Some of the kinetic energy is transferred to the body, causing internal injuries and, occasionally, death. The aim of this study was to investigate if apnea and other pathophysiological effects after BABT is a vagally mediated reflex. Sixteen anesthetized pigs wearing body armor, of which five were vagotomized, were shot with a standard 7.62 mm assault rifle. These animals were compared with control animals (n = 8), shot with blank ammunition. We performed bilateral vagotomy before the shot and assessed the outcome on the apnea period, respiration, circulation, and brain function. Animals were monitored during a 2-hour period after the shot. Nonvagotomized animals had a mean apnea period of 22 (6-44) seconds. This group also showed a significant decrease in oxygen saturation compared with control animals. Furthermore, electroencephalogram-changes were more pronounced in nonvagotomized animals. In contrast, vagotomized animals were protected from apnea and showed only a minor decrease in oxygen saturation. All exposed animals showed impaired circulation, and postmortem examination revealed a pulmonary contusion. This study shows that apnea after BABT is a vagally mediated reflex that can be inhibited by bilateral vagotomy. Our results indicate that the initial apnea period is an important factor for hypoxia after BABT. Supported ventilation should begin immediately if the affected person is unconscious and suffers from apnea. It should continue until the neurologic paralysis disappears and sufficient spontaneous breathing begins.

Fos-like immunoreactivity and thirst following hyperosmotic loading in rats with subdiaphragmatic vagotomy.

PubMed

Starbuck, Elizabeth M; Wilson, Wendy L; Fitts, Douglas A

2002-03-29

If receptors in the gut relay information about increases in local osmolality to the brain via the vagus nerve, then vagotomy should diminish this signaling and reduce both thirst and brain Fos-like immunoreactivity (Fos-ir). Water intake in response to hypertonic saline (i.p. or i.g., 1 M NaCl, 1% BW; i.g., 0.6 M NaCl, 0.5% BW) was reduced during 120 min in rats with subdiaphragmatic vagotomy (VGX) compared to sham-VGX rats. Brain Fos-ir was examined in response to both i.g. loads. After the smaller load, VGX greatly reduced Fos-ir in the supraoptic nucleus (SON) and the magnocellular and parvocellular areas of the paraventricular nucleus (PVN). Fos-ir in the subfornical organ (SFO) and nucleus of the solitary tract (NTS) was not affected. After the larger load, VGX significantly reduced Fos-ir in the parvocellular PVN and in the NTS, but not in the other regions. Thus, decreased water intake by VGX rats was accompanied by decreased Fos-ir in the parvocellular PVN after the same treatments, indicating a role for the abdominal vagus in thirst in response to signaling from gut osmoreceptors. The decreased water intake in the VGX group was not reflected as a decrease in Fos-ir in the SFO. Absorption of the larger i.g. load may have activated Fos-ir through more rapidly increasing systemic osmolality, thereby obscuring a role for the vagus at this dose in the SON and magnocellular PVN.

Laparotomy and proximal gastric vagotomy in Zollinger-Ellison syndrome: results of a 16-year prospective study.

PubMed

McArthur, K E; Richardson, C T; Barnett, C C; Eshaghi, N; Smerud, M J; McClelland, R N; Feldman, M

1996-06-01

Pharmacological control of gastric acid hypersecretion in the Zollinger-Ellison syndrome has steadily improved, but medical treatment does not address the underlying tumor. The objective of this study was to evaluate the long-term effectiveness of a surgical approach to both tumor and acid hypersecretion in 22 patients with the Zollinger-Ellison syndrome. Patients underwent laparotomy to resect tumors, combined with vagotomy to reduce acid secretion, followed by postoperative antisecretory therapy, if necessary. No surgical mortality or serious morbidity occurred. Tumor was found at laparotomy in nine patients (41%) and during long-term follow-up in an additional two patients (9%). Ten-year survival is 81%, with a long-term cure rate of at least 14%. Most patients (86%) have had long-term inhibition of acid secretion. Eight patients have discontinued regular use of acid-inhibiting medications. Patients requiring medication need less of it, and they have an improved acid inhibitory response to medication for up to 16 yr after surgery. Cure of the Zollinger-Ellison syndrome is possible in a minority of patients. Acid secretion can be safely reduced in almost all patients with laparotomy/vagotomy, usually allowing discontinuation, or reduced dose, of acid-inhibiting drugs. Long-term survival and quality of life are generally excellent.

Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Mckenna, Susan

1991-01-01

The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

Four-year to Eight-year Results of Vagotomy and Simple Drainage for Benign Lesser Curve Gastric Ulcer

PubMed Central

Burge, H.; Gill, A. Morton; Maclean, C.; Stedeford, R.

1970-01-01

The results of vagotomy and simple drainage for recurrent benign lesser curve gastric ulcer are recorded. Seventy-two consecutive cases were treated from 1962 to 1965. The follow-up is therefore from five to eight years. In only two cases did the ulcer fail to heal and remain healed. Four years after operation both these had persistent ulceration and persistent gastric retention. Both have apparently been cured by gastrojejunostomy done to improve gastric drainage. ImagesFIG. 1FIG. 2FIG. 3 PMID:5451588

Technique of laparoscopic posterior truncal vagotomy and anterior seromyotomy using endoscopic esophogeal transillumination

NASA Astrophysics Data System (ADS)

Reed, David M.; Tortella, Bartholomew J.; Dolan, William V.; Pennino, Ralph P.; Treat, Michael R.

1993-05-01

The unprecedented rapid and successful adoption of laparoscopic cholecystectomy has prompted the evaluation of converting other standard open surgical procedures to a laparoscopic technique. A wide variety of laparoscopic acid reduction procedures have been successfully accomplished by groups in this country and abroad. Our group reviewed the literature on the many types of open peptic ulcer operations, as well as the ones performed laparoscopically. We elected to perfect the technique of posterior truncal vagotomy and anterior seromyotomy (PTVAS). After extensive animal laboratory work, we performed PTVAS on four patients with documented recurrent peptic ulcer disease. We describe our technique as it evolved and in particular note the usefulness of endoscopic esophageal transillumination. In addition, we report our results and discuss their implications.

[Recurrent ulcers following selective proximal vagotomy (10 years' results)].

PubMed

Saenko, V F; Dikusarov, A V; Polinkevich, B S; Vashchenko, A E; Pustovit, A A

1989-01-01

The results of selective proximal vagotomy (SPV) in 1266 patients were studied. In 778 (61.5%) SPV alone was performed, in 488 (38.5%)--SPV with drainage operation: Finney pyloroplasty--in 249 (51%), Heineke-Mikulicz pyloroplasty--in 77 (15.8%), Jaboulay gastroduodenostomy--in 75 (15.4%), anterior hemipylorectomy--in 49 (10%), other drainage operations--in 38 (7.8%). After isolated SPV, excellent and good results were noted in 81.5% of the patients, satisfactory--in 11.1%, unsatisfactory--in 7.4%; after SPV with drainage operation--in 87.7%, 9.6% and 2.7%, respectively. An ulcer recurrence after SPV was revealed in 58 (7.4%), after SPV with drainage operation--in 13 (2.7%) of the patients examined. In 90% of cases, an ulcer recurrence developed at the pyloroduodenal zone, in 10%--in the stomach. The incidence of ulcer recurrence was 8.7% after operations performed by surgeons, who had not enough experience with the SPV performance, and 4.4%--by experienced surgeons. In 46.5% of cases, in recurrent ulcer, the conservative treatment was performed, and the remaining patients underwent surgery (antrumectomy, revagotomy etc.).

Treatment of severe peptic esophageal stricture with Roux-en-Y partial gastrectomy, vagotomy, and endoscopic dilation. A follow-up study.

PubMed

Salo, J A; Ala-Kulju, K V; Heikkinen, L O; Kivilaakso, E O

1991-04-01

Eleven patients with dysphagia caused by severe esophageal stricture (length 2 to 10 cm) resulting from reflux esophagitis were treated with fibroendoscopic dilation (Eder-Puestow) and Roux-en-Y partial gastrectomy with vagotomy during 10 years (1979 to 1988). There was no operative mortality, but complications developed in three patients: One patient had a mediastinal abscess demanding thoracotomy as a result of esophageal perforation after dilatation; one had postoperative pneumonia; and one patient had ileus. After a mean follow-up of 4 years (range 1 to 10 years) esophagitis healed in all cases, as judged by endoscopy. Eight patients were asymptomatic, but three had slight transient dysphagia. Postoperatively one to eight dilations (average three to four) were needed to relieve dysphagia in the first postoperative year, but later the stricture healed in every case. Postoperative pH measurement was performed in six latest patients and showed complete absence of reflux in all cases. It is concluded that Roux-en-Y partial gastrectomy with vagotomy and endoscopic dilation is an effective, simple, and safe procedure in the management of severe peptic esophageal (acid or alkaline esophagitis) stricture. However, occasional postoperative dilations at the outpatient clinic are often needed in severe cases in the first postoperative year.

The centenary of Lester Dragstedt--fifty years of therapeutic vagotomy.

PubMed Central

Modlin, I. M.; Darr, U.

1994-01-01

Lester Reynolds Dragstedt was trained initially as a physiologist and subsequently became a surgeon. He achieved renown not only because of his intellectual and technical skills, but because he was able to utilize physiological principles to define the development of surgical procedures. A humble upbringing in Anaconda, Montana was followed by a scientific education in Chicago. His brief background in surgery was obtained during a two year period spent mostly in Vienna and Budapest. At the University of Chicago, he pioneered the development of therapeutic vagotomy in the treatment of peptic ulcer disease. His research interests were many and varied, ranging from the toxemia of intestinal obstruction to the quest for a pancreatic hormone which might regulate fat metabolism. After retiring as Chairman of Surgery at the University of Chicago, he assumed a research position in surgery at the University of Florida in Gainesville. Dragstedt was a creative scientist, a superlative clinical surgeon, and a teacher honored by his pupils. The example of his life confirms the benefit of scientific inquiry when applied to clinical and surgical practice. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:7502534

Towards selecting the vagotomy and avoiding diarrhoea.

PubMed

Milewski, P J

1990-02-01

A retrospective review was carried out of 148 consecutive personal truncal vagotomies and anterior pylorectomies (TV + P), median follow-up 5.0 years. The recurrent ulcer rate was 6/148 (4.1%) for suspected (SRU) and 5/148 (3.4%) for proven ones (RU). This led to one death from RU. Thirty-six patients (24.3%) developed postvagotomy diarrhoea (PVD). Two of these were graded Visick IV because their occupations made PVD particularly inconvenient. These results are similar to those for TV and pyloroplasty, despite the slightly more destructive nature of pylorectomy. There were nine patients in whom evidence of associated bowel disease had been documented before or during operation. The occurrence of such evidence was significantly more frequent in the PVD group (6/36 vs. 3/112 patients, P = 0.014), suggesting either a summation of effects due to the bowel disease and the operation or that the diagnosis of PVD was sometimes incorrect. Of the six in the PVD group, two were in Visick Grade II because of their PVD, and four in Visick grade III or IV, but in one of these SRU was the main cause of the poor result, and in two the PVD was subsidiary to vomiting or dumping. One further patient in Visick III due to PVD had diverticular disease diagnosed after operation. Thus there were identifiable factors (occupation, associated bowel disorder) which could have been used to predict seven of the unsatisfactory results due partly or completely to PVD. TV + P is an effective operation for duodenal ulcer but, as with TV + pyloroplasty (though to no greater an extent), severe diarrhoea may occasionally mar the result.(ABSTRACT TRUNCATED AT 250 WORDS)

Revision with Totally Hand-Sewn Gastrojejunostomy and Vagotomy for Refractory Marginal Ulcer after Laparoscopic Roux-en-Y Gastric Bypass.

PubMed

Chang, Po-Chih; Huang, Chih-Kun; Rajan, Mahendra; Hsin, Ming-Che

2016-05-01

Marginal ulcer is not infrequent after laparoscopic Roux-en-Y gastric bypass and could result in undesirable complications, such as intractability, bleeding, or perforation. Those patients who failed medical therapy, regarded as refractory marginal ulcers, may be considered as candidates for revisional surgery. Herein, we make a video presentation of a laparoscopic revisional procedure for refractory marginal ulcer. A 29-year-old morbidly obese woman (initial body mass index 37.1 kg/m(2)), a non-smoker, presented with persistent epigastric pain 3 months after initial laparoscopic Roux-en-Y gastric bypass at another institution. After an exhaustive work-up there, only the gastroendoscopy revealed a marginal ulcer and she underwent medical treatment (proton pump inhibitor and sucralfate) for 3 months, but the patient's symptom aggravated and the serial gastroendoscopies still confirmed the marginal ulcer without obvious resolution after a total of 4 months proton pump inhibitor therapy, suggesting failure of medical treatment and intractability. Laparoscopic revisional procedure with totally hand-sewn gastrojejunostomy and vagotomy was performed to relieve her intractable condition. The procedure took 130 min, without any intra-operative complications. Blood loss was 80 mL. The patient had an uneventful postoperative course, and the postoperative hospital stay was 3 days. She was relieved of her symptoms after this revisional surgery, and a subsequent gastroendoscopy 15 months later showed no marginal ulcers. Though long-term follow-up is needed to draw a definite conclusion, totally hand-sewn gastrojejunostomy and vagotomy remains a practicable revisional procedure to relieve refractory marginal ulcers.

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

PubMed Central

Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy E

2016-01-01

Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/- mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/- mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. PMID:27341335

[Automated morphometric evaluation of the chromatin structure of liver cell nuclei after vagotomy].

PubMed

Butusova, N N; Zhukotskiĭ, A V; Sherbo, I V; Gribkov, E N; Dubovaia, T K

1989-05-01

The morphometric analysis of the interphase chromatine structure of the hepatic cells nuclei was carried out on the automated TV installation for the quantitative analysis of images "IBAS-2" (by the OPTON firm, the FRG) according to 50 optical and geometric parameters during various periods (1.2 and 4 weeks) after the vagotomy operation. It is determined that upper-molecular organisation of chromatine undergoes the biggest changes one week after operation, and changes of granular component are more informative than changes of the nongranular component (with the difference 15-20%). It was also revealed that chromatine components differ in tinctorial properties, which are evidently dependent on physicochemical characteristics of the chromatine under various functional conditions of the cell. As a result of the correlation analysis the group of morphometric indices of chromatine structure was revealed, which are highly correlated with level of transcription activity of chromatine during various terms after denervation. The correlation quotient of these parameters is 0.85-0.97. The summing up: vagus denervation of the liver causes changes in the morphofunctional organisation of the chromatine.

Stimulation of gastrin release and gastric secretion: effect of bombesin and a nonapeptide in fistula dogs with and without fundic vagotomy.

PubMed

Hirschowitz, B I; Gibson, R G

1978-01-01

Bombesin and a synthetic bombesin nonapeptide were studied by intravenous infusion at a dose of 0.5 microgram.kg-1.h-1 for 4 h in 7 dogs with esophagostomy and gastric fistula. In 3 of the dogs who had highly selective (fundic) vagotomy, mean integrated gastrin output over 4 h was double that in the 4 dogs with vagi intact during both nonapeptide (1,554 vs. 700 pg.ml-1.4 h-1) and bombesin infusion (2,442 vs. 1,440 pg.ml-1.4 h-1). Peak concentrations of serum gastrin reached during bombesin (490 +/- 100 vs. 320 +/- 90) were higher than those during nonapeptide infusion (270 +/- 40 vs. 160 +/- 28 pg/ml) in the vagotomized and intact dogs, respectively. The difference between vagotomized and vagally intact dogs suggests that the fundic vagotomy removed an inhibitor of gastrin release from the innervated antrum. Despite these differences in gastrin release, gastric acid output with the two peptides was the same (49--52 mEq/4 h) whether the fundus was denervated or innervated. This suggests that bombesin may stimulate gastric acid secretion by the release of an additional secretagogue which is not measured by the gastrin assay. Neither of the two inhibitors of gastrin release--antral acidification to pH 1.4 or less or atropine (100 microgram/kg)-- inhibited gastrin release by bombesin, even though the atropine reduced acid output by 80%. Bombesin is a potent gastric stimulus whose action is only partly explained by the measured gastrin release.

[Postbular duodenal ulcer. Problems of diagnosis and treatment. Role of vagotomy in surgical treatment].

PubMed

Juvara, I; Rădulescu, D; Păcescu, E; Dragomirescu, C; Gavrilescu, S

1977-01-01

A number of 43 cases is presented, of post-bulbar duodenal ulcers in which surgery has been performed between 1965 and 1974, of which 30 were located in the first portion of the duodenum, in the postbulbar area, and 15 in the second portion, above the ampula of Vater. Problems of terminology and pathological anatomy are discussed, especially in connection with the symptomatology, complications, methodology of investigations and treatment of post-bulbar ulcers. The particular frequency is stressed, of complicated clinical forms, with stenosis and hemorrhagies, and a detailed description is made of atypical forms, with misleading, predominantly biliary or pancreatic symptomatology. Conditions are stressed, of the radiologic gastroduodenal exploration, of major importance in the diagnosis preceding surgery, as well as of pre- and intra-surgery cholangiography. The risk must be carefully evaluated, in the choice of the surgical method, and exeresis of the ulcer must be balanced with the risk of its continued presence. Priority should be given to th risks entailed by surgery. The choice solution in many cases is vagotomy associated to exclusion resection or to gastric derivation.

Morphological effects of chronic bilateral phrenectomy or vagotomy in the fetal lamb lung.

PubMed Central

Alcorn, D; Adamson, T M; Maloney, J E; Robinson, P M

1980-01-01

The relationship between fetal espiratory activity and fetal lung development has been studied at the cellular level using two experimental models. Chronic bilateral phrenectomy over a period of 20-28 days during the last trimester of the fetal lamb resulted in hypoplastic lungs, although cellular maturity, as indicated by the presence of alveolar epithelial Type II cells, was present. In the lungs from fetal lambs undergoing sham operations for a similar time course there was evidence of enhanced alveolar proliferation when compared with lungs from normal fetal sheep of a similar gastational age, most probably as a result of operative stress. Following chronic bilateral vagotomy no changes in size or histology of the fetal lamb lungs were detected. At an ultrastructural level, however, inclusions of Type II cells consistently showed the loss of the typical osmiophilic lamellated appearance. These results indicate the importance of the fetal breathing apparatus in maintaining a volume of lung liquid which is adequate for normal pulmonary development, particularly during the phase in which alveoli are formed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:7429961

Effect of antisecretory agents and vagotomy on healing of chronic cysteamine-induced duodenal ulcers in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulsen, S.S.; Raaberg, L.; Therkelsen, K.

1986-07-01

Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphologymore » of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.« less

[Anterior seromyotomy of the body and the functional part of the stomach combined with posterior truncal vagotomy and ulcer excision in the surgical treatment of complicated stomach ulcer].

PubMed

Petrov, V I; Sytnik, A P; Gorbunov, V N; KOrenev, N N; Naumov, B A; Gordeev, S A

1990-07-01

Anterior seromyotomy of the body and fundus of the stomach was combined with posterior truncal vagotomy and excision of the ulcer in 23 patients with gastric ulcer complicated by bleeding or perforation. Seventeen patients had chronic ulcers of the body of the stomach (type I), 3 patients had concurrent ulcers (type II), and 3 more patients had acute ulcers of the body of the stomach. Operation was undertaken for active bleeding from the ulcer in 20 patients and for perforating ulcer in 3 patients. One patient died. Mild disorders of evacuation of an aqueous barium sulfate suspension from the stomach were noted in 4 patients.

The effect of vagotomy on sodium reabsorption and renin release in anaesthetized dogs subjected to 60 degrees head-up tilt.

PubMed Central

DiBona, G F; Johns, E J; Osborn, J L

1981-01-01

1. Anaesthetized dogs were subjected to two 15 min periods of 60 degrees head-up tilt. Renal perfusion pressure was regulated to minimize changes during tilting. 2. In both intact and vagotomized animals there was a fall in systemic arterial pressure and a rise in heart rate. In both intact and vagotomized animals glomerular filtration rate fell slightly during the first tilt but remained unchanged in the second tilt period. Renal blood flow was unchanged throughout. 3. Both absolute and fractional excretions of sodium were reduced in intact animals subjected to the two consecutive periods of tilt. Following vagotomy these responses were as large as those observed in intact animals. 4. Tilting caused an increase in renin secretion from the kidney in both tilting periods to which the intact animals were subjected. In the vagotomized animals the increase in renin secretion was as large as that observed in intact animals. 5. The results of the present study show that, under the experimental conditions used, vagal afferent activity had no measurable effect on the decreases in sodium excretion or increases in renin secretion mediated by the renal nerves during short periods of 60 degrees head-up tilt. PMID:7033504

In vitro motility changes in Roux limb after Roux-en-Y reconstruction.

PubMed

Dogan, N; Gokakin, A K; Koyuncu, A; Bagcivan, I; Aydin, C; Topcu, O; Yildirim, S

2014-01-01

The aim of this study is to compare the motility of Roux limb with that of normal segment. Rats were divided into 3 equal groups as control, Roux-en-Y (Group A) and Roux-en-Y with vagotomy (Group B). Only midline incision and manipulations were applied in control group. Following distal gastrectomy, Roux-en-Y reconstruction was applied in Group A, while vagotomy Roux-en-Y gastrojejunostomy was applied in Group B. Rats were sacrificed 1 month later by cervical dislocations under anesthesia. The obtained jejunal segments were cut into four equal parts. The bath was 37 °C warm while 95 % O2 and 5 % CO2 gases were supplied in 10 ml bicarbonate Krebs' solution. KCl responses were similar in all three groups. Acetylcholine contraction responses in the vagotomy and non-vagotomy Roux-en-Y groups was higher than in those in control group significantly (p < 0.05). This response in vagotomy Roux-en-Y group was also higher than that in non-vagotomy group (p < 0.05). The induced electrical field stimulation contraction response in the vagotomy + Roux-en-Y group was lower than those in control group and non-vagotomy group (p < 0.05). These results show that muscarinic receptor density and/or function may increase after vagotomy and non-vagotomy group operation, and vagotomy may contribute to this increase. The decrease in electrical signal response in vagotomy Roux-en-Y group may depend on the decrease in acetylcholine oscillation from the cholinergic nerve ending (Tab. 1, Fig. 5, Ref. 25).

Abnormal oral glucose tolerance and glucose malabsorption after vagotomy and pyloroplasty. A tracer method for measuring glucose absorption rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radziuk, J.; Bondy, D.C.

1982-11-01

The mechanisms underlying the abnormal glucose tolerance in patients who had undergone vagotomy and pyloroplasty were investigated by measuring the rates of absorption of ingested glucose and the clearance rate of glucose using tracer methods. These methods are based on labeling a 100-g oral glucose load with (1-/sup 14/C)glucose and measuring glucose clearance using plasma levels of infused (3-/sup 3/H)glucose. The rate of appearance of both ingested and total glucose is then calculated continuously using a two-compartment model of glucose kinetics. It was found that about 30% of the ingested glucose (100 g) failed to appear in the systemic circulation.more » That this was due to malabsorption was confirmed using breath-hydrogen analysis. The absorption period is short (101 +/- 11 min) compared with normal values but the clearance of glucose is identical to that in control subjects, and it peaks 132 +/- 7 min after glucose loading. The peak plasma insulin values were more than four times higher in patients than in normal subjects, and this may afford an explanation of rates of glucose clearance that are inappropriate for the short absorption period. The combination of glucose malabsorption and this clearance pattern could yield the hypoglycemia that may be observed in patients after gastric surgery.« less

Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats.

PubMed

LeSagE, G; Alvaro, D; Benedetti, A; Glaser, S; Marucci, L; Baiocchi, L; Eisel, W; Caligiuri, A; Phinizy, J L; Rodgers, R; Francis, H; Alpini, G

1999-07-01

To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats). After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels. Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin. Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.

[Surgical treatment of anastomosis ulcers. 1. Short-term results].

PubMed

Lüders, K; Fellmann, E; März, E

1980-02-14

Records of 151 patients from the years 1964--1979 with anastomotic ulcers including relapses of ulcers after vagotomy reveal a total lethality of 3.3 per cent after reoperation. Re-gastrectomy with or without additional vagotomy shows a lethality of 5.7 per cent. If vagotomy alone is carried out there were no lethality and nearly no serious complications. Gastrectomy because of recurrent peptic ulcer after primary vagotomy has also no lethality. With regard to less serious postoperative complications including lethality after vagotomy instead of re-gastrectomy we should favour vagotomy for re-operation. Our further examinations will show whether this attitude is justified by long-term results after re-operation of the stomach in consequence of recurrent pepti ulcer.

Endoscopic Obliteration for Bleeding Peptic Ulcer

PubMed Central

Zawadzki, J.J. J.; Gajda, A.G. G.; Kamiński, P. Ł.; Lembas, L.; Bielecki, K.

1997-01-01

A group of 133 patients treated for bleeding peptic ulcer in our Department, is reviewed. Within several hours of admission, all patients underwent upper gastrointestinal tract gastroscopy and obliteration of the bleeding ulcer. Bleeding gastric ulcers were found in 41 patients, and duodenal ulcers in 92 patients. Patients were classified according to the Forrest scale: IA – 11 patients, IB – 49 patients, IIA – 35 patients, lIB – 40 patients. In 126 (94.7%) patients the bleeding was stopped, and 7 required urgent surgery: 3 patients with gastric ulcer underwent gastrectomy, and 4 with duodenal ulcer – truncal vagotomy with pyloroplasty and had the bleeding site underpinned. Fifty-five patients underwent elective surgery: gastrectomy and vagotomy (18 patients with gastric ulcer), highly selective vagotomy (25 patients with duodenal ulcer) and truncal vagotomy and pyloroplasty (12 patients with duodenal ulcer). None of the patients was observed to have recurrent bleeding. PMID:18493453

[Comparative results of surgical treatment for perforating and bleeding pyloroduodenal ulcers].

PubMed

Gorbunov, V N; Sytnik, A P; Korenev, N N; Gordeev, S A; Stoliarchuk, E V; Urzhumtseva, G A

1998-01-01

Results of treatment of 1309 patients with perforated and bleeding pyloroduodenal ulcers for 20-years period have been analysed. Resection of the stomach performed in 85 cases resulted in high postoperative lethality which made up in bleeding ulcers 14.8%. Drainage operations of the stomach with excision or suturing of ulcer combined with bilateral truncal vagotomy was performed in 60 patients, postoperative lethality rate being 8.4%. 128 patients underwent selective proximal vagotomy together with pyloro- and duodenoplasty, lethality rate being 1.6%. Combined vagotomy (posterior truncal and anterior sero-muscular) with excision of ulcer, transversal pyloroplasty and duodenoplasty was carried out in 1036 patients (postoperative lethality--2.4%). Excellent and good functional results were achieved in 79.6% of the patients.

The influence of autonomic interventions on the sleep-wake-related changes in gastric myoelectrical activity in rats.

PubMed

Huang, Y M; Yang, C C H; Lai, C J; Kuo, T B J

2011-06-01

Significant changes in autonomic activity occur at sleep-wake transitions and constitute an ideal setting for investigating the modulatory role of the autonomic nervous system on gastric myoelectrical activity (GMA). Using continuous power spectral analysis of electroencephalogram, electromyogram, and electrogastromyogram (EGMG) data from freely moving rats that had undergone chemical sympathetomy and/or truncal vagotomy, sleep-wake-related fluctuations in GMA were compared among the intervention groups. The pattern and extent of fluctuations in EGMG power across the sleep-wake states was blunted most significantly in rats undergoing both chemical sympathectomy and truncal vagotomy. The effect of these interventions also varied with respect to the transition between different sleep-wake states. The most prominent influences were observed between active waking and quiet sleep and between paradoxical sleep and quiet sleep. The sleep-wake-related fluctuations in EGMG power are a result of joint contributions from both sympathetic and vagal innervation. Vagotomy mainly resulted in a reduction in EGMG power, while the role of sympathetic innervation was unveiled by vagotomy and this was reflected most obviously in the extent of the fluctuations in EGMG power. © 2011 Blackwell Publishing Ltd.

Modulation of gastric contractions in response to tachykinins and bethanechol by extrinsic nerves.

PubMed Central

Holzer-Petsche, U.

1991-01-01

1. Extrinsic reflexes elicited by changes in gastric wall tension play an important role in regulating gastric tone. The present study investigated whether such reflexes modulate gastric contractions induced by close arterially administered neurokinin A (NKA), substance P (SP), SP-methylester and bethancehol in anaesthetized rats. 2. Reflex pathways were acutely interrupted by either subdiaphragmatic vagotomy or prevertebral ganglionectomy. C-fibre afferent nerve activity was abolished by pretreating rats with capsaicin 10 to 16 days before the experiments. 3. The order of potency in inducing gastric contractions was NKA greater than SP greater than bethanechol. SP-methylester was markedly less effective than SP and its effects did not fit sigmoid dose-response curves (DRCs). The maximal responses to NKA, SP, and bethanechol were similar, whilst the DRC for SP was significantly flatter than those for NKA or bethanechol. Pretreatment of the rats with the peptidase inhibitors phosphoramidon or captopril did not increase the contractile response to SP. 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left. 5. Capsaicin pretreatment did not change the DRC for NKA in rats with intact vagus but shifted that for bethanechol to the left. The leftward of the DRC for NKA caused by vagotomy was prevented in capsaicin-pretreated rats whereas the vagotomy-induced shift of the DRC for bethanechol remained unaltered. The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment. 6. These data may be interpreted as demonstrating two neuronal mechanisms for modulating drug-induced gastric contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1717093

Modulation of gastric contractions in response to tachykinins and bethanechol by extrinsic nerves.

PubMed

Holzer-Petsche, U

1991-08-01

1. Extrinsic reflexes elicited by changes in gastric wall tension play an important role in regulating gastric tone. The present study investigated whether such reflexes modulate gastric contractions induced by close arterially administered neurokinin A (NKA), substance P (SP), SP-methylester and bethancehol in anaesthetized rats. 2. Reflex pathways were acutely interrupted by either subdiaphragmatic vagotomy or prevertebral ganglionectomy. C-fibre afferent nerve activity was abolished by pretreating rats with capsaicin 10 to 16 days before the experiments. 3. The order of potency in inducing gastric contractions was NKA greater than SP greater than bethanechol. SP-methylester was markedly less effective than SP and its effects did not fit sigmoid dose-response curves (DRCs). The maximal responses to NKA, SP, and bethanechol were similar, whilst the DRC for SP was significantly flatter than those for NKA or bethanechol. Pretreatment of the rats with the peptidase inhibitors phosphoramidon or captopril did not increase the contractile response to SP. 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left. 5. Capsaicin pretreatment did not change the DRC for NKA in rats with intact vagus but shifted that for bethanechol to the left. The leftward of the DRC for NKA caused by vagotomy was prevented in capsaicin-pretreated rats whereas the vagotomy-induced shift of the DRC for bethanechol remained unaltered. The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment. 6. These data may be interpreted as demonstrating two neuronal mechanisms for modulating drug-induced gastric contractions. First, the contractions themselves activate a vago-vagal negative feedback involving capsaicin-sensitive afferents. Second, NKA, and to a lesser degree SP, seem to induce a nonvagal non-splanchnic mechanism which via capsaicin

Effects of gastric pacing on gastric emptying and plasma motilin

PubMed Central

Yang, Min; Fang, Dian-Chun; Li, Qian-Wei; Sun, Nian-Xu; Long, Qing-Lin; Sui, Jian-Feng; Gan, Lu

2004-01-01

AIM: To investigate the effects of gastric pacing on gastric emptying and plasma motilin level in a canine model of gastric motility disorders and the correlation between gastric emptying and plasma motilin level. METHODS: Ten healthy Mongrel dogs were divided into: experimental group of six dogs and control group of four dogs. A model of gastric motility disorders was established in the experimental group undergone truncal vagotomy combined with injection of glucagon. Gastric half-emptying time (GEt1/2) was monitored with single photon emission computerized tomography (SPECT), and the half-solid test meal was labeled with an isotope 99mTc sulfur colloid. Plasma motilin concentration was measured with radioimmunoassay (RIA) kit. Surface gastric pacing at 1.1-1.2 times the intrinsic slow-wave frequency and a superimposed series of high frequency pulses (10-30 Hz) was performed for 45 min daily for a month in conscious dogs. RESULTS: After surgery, GEt1/2 in dogs undergone truncal vagotomy was increased significantly from 56.35 ± 2.99 min to 79.42 ± 1.91 min (P < 0.001), but surface gastric pacing markedly accelerated gastric emptying and significantly decreased GEt1/2 to 64.94 ± 1.75 min (P < 0.001) in animals undergone vagotomy. There was a significant increase of plasma level of motilin at the phase of IMCIII (interdigestive myoelectrical complex, IMCIII) in the dogs undergone bilateral truncal vagotomy (baseline vs vagotomy, 184.29 ± 9.81 pg/ml vs 242.09 ± 17.22 pg/ml; P < 0.01). But plasma motilin concentration (212.55 ± 11.20 pg/ml; P < 0.02) was decreased significantly after a long-term treatment with gastric pacing. Before gastric pacing, GEt1/2 and plasma motilin concentration of the dogs undergone vagotomy showed a positive correlation (r = 0.867, P < 0.01), but after a long-term gastric pacing, GEt1/2 and motilin level showed a negative correlation (r = -0.733, P < 0.04). CONCLUSION: Surface gastric pacing with optimal pacing parameters can improve

Gastric vagus mediates immobilization-induced hypocalcemia in rats.

PubMed

Ma, J; Aou, S; Matsui, H; Hori, T

1993-09-01

The involvement of the parasympathetic nervous system in the etiology of stress-induced hypocalcemia was investigated in the rat. Atropine methyl bromide (0.1 and 0.6 mg/kg ip) given 20 min before immobilization (IMB) was observed to suppress the induction of hypocalcemia in a dose-dependent manner. A vagotomy of the bilateral cervical trunks also abolished the IMB-induced hypocalcemia. A vagotomy on either the thyroid/parathyroid branches or the celiac branches had no effect on the IMB-induced hypocalcemia, but a vagotomy on the gastric branches completely abolished it. Pretreatment with either secretin (2 and 6 micrograms/kg ip), an inhibitor of gastrin release, or cimetidine (5 and 10 mg/kg ip), a histamine H2-receptor antagonist, diminished the IMB-induced hypocalcemia. The concentration of serum gastrin increased significantly during IMB. It is thus concluded that the decreased levels of plasma calcium caused by IMB are due to the activation of the vagus innervating the stomach. Gastrin and histamine are also involved as a consequence of the activation of the vagus.

Association of vagus nerve severance and decreased risk of subsequent type 2 diabetes in peptic ulcer patients: An Asian population cohort study.

PubMed

Wu, Shih-Chi; Chen, William Tzu-Liang; Fang, Chu-Wen; Muo, Chih-Hsin; Sung, Fung-Chang; Hsu, Chung Y

2016-12-01

Vagus nerve may play a role in serum glucose modulation. The complicated peptic ulcer patients (with perforation or/and bleeding) who received surgical procedures with or without vagotomy provided 2 patient populations for studying the impact of vagus nerve integrity. We assessed the risk of developing type 2 diabetes in peptic ulcer patients without and with complications by surgical treatment received in a retrospective population study using the National Health Insurance database in Taiwan.A cohort of 163,385 patients with peptic ulcer and without Helicobacter pylori infection in 2000 to 2003 was established. A randomly selected cohort of 163,385 persons without peptic ulcer matched by age, sex, hypertension, hyperlipidemia, Charlson comorbidity index score, and index year was utilized for comparison. The risks of developing diabetes in both cohorts and in the complicated peptic ulcer patients who received truncal vagotomy or simple suture/hemostasis (SSH) were assessed at the end of 2011.The overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 (95% confidence interval [CI] = 1.40-1.47) based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and SSH or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41-0.56).Peptic ulcer patients have an elevated risk of developing type 2 diabetes. Moreover, there were associations of vagus nerve severance and decreased risk of subsequent type 2 diabetes in complicated peptic ulcer patients.

Association of vagus nerve severance and decreased risk of subsequent type 2 diabetes in peptic ulcer patients

PubMed Central

Wu, Shih-Chi; Chen, William Tzu-Liang; Fang, Chu-Wen; Muo, Chih-Hsin; Sung, Fung-Chang; Hsu, Chung Y.

2016-01-01

Abstract Vagus nerve may play a role in serum glucose modulation. The complicated peptic ulcer patients (with perforation or/and bleeding) who received surgical procedures with or without vagotomy provided 2 patient populations for studying the impact of vagus nerve integrity. We assessed the risk of developing type 2 diabetes in peptic ulcer patients without and with complications by surgical treatment received in a retrospective population study using the National Health Insurance database in Taiwan. A cohort of 163,385 patients with peptic ulcer and without Helicobacter pylori infection in 2000 to 2003 was established. A randomly selected cohort of 163,385 persons without peptic ulcer matched by age, sex, hypertension, hyperlipidemia, Charlson comorbidity index score, and index year was utilized for comparison. The risks of developing diabetes in both cohorts and in the complicated peptic ulcer patients who received truncal vagotomy or simple suture/hemostasis (SSH) were assessed at the end of 2011. The overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 (95% confidence interval [CI] = 1.40–1.47) based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and SSH or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41–0.56). Peptic ulcer patients have an elevated risk of developing type 2 diabetes. Moreover, there were associations of vagus nerve severance and decreased risk of subsequent type 2 diabetes in complicated peptic ulcer patients. PMID:27930533

Mechanism of pancreatic polypeptide release in man.

PubMed

Adrian, T E; Besterman, H S; Cooke, T J; Bloom, S R; Barnes, A J; Russell, R C

1977-01-22

Pancreatic polypeptide (P.P.) is a potent hormonal peptide which has been isolated from the pancreas. Its role in human physiology and pathology is not yet established. After a standard hospital lunch the plasma concentration of P.P. showed a rapid and identical rise in 10 healthy controls, 11 duodenal-ulcer patients, and 6 post-vagotomy patients but remained undetectable in 4 totally pancreatectomised subjects. In contrast plasma-P.P. was unaffected by intravenous administration of glucose, aminoacids, or fat. However, during intravenous infusion of caerulein, a cholecystokinin analogue, P.P. rose by nearly five-fold, and an even greater rise was seen after intravenous injection of Boots secretin. In 19 duodenal-ulcer patients insulin hypoglycaemia produced a rapid rise in plasma-P.P. but this did not occur in any of the 17 patients studied after a truncal vagotomy. Thus P.P. is released by oral but not intravenous nutriments and the existence of an entero-P.P. axis is postulated. One component of this axis may be the vagal innervation but the normal postprandial rise seen after vagotomy suggests that other control mechanisms, such as the intestinal hormones, are more important.

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

PubMed Central

Watt, P C; Sloan, J M; Donaldson, J; Campbell, G; Kennedy, T L

1984-01-01

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes. PMID:6725597

Peripheral functional organisation of vagally evoked gastric motor responses in the ferret.

PubMed Central

Andrews, P L; Lawes, I N; Bower, A J

1980-01-01

The aims of the present study were to determine the relative amplitudes of intragastric motor responses evoked by different vagal branches and to establish whether the effects of acute or chronic vagotomy could be predicted from these data. Intragastric pressure responses to electrical stimulation of the vagus were measured in urethane-anaesthetised ferrets and acute or chronic vagotomies were performed. The results show that the left and right cervical vagi were equipotential and fully overlaped each other. Their contributions to the dorsal trunk were equipotential and fully overlapping and so were their contributions to the ventral trunk. The dorsal trunk was more effective than the ventral trunk and there was total functional overlap between these two trunks. Vagal evoked gastric motor responses of the ferret are apparently organised in a different way from vagally induced acid secretion or hormone release in the cat. Acute removal of a trunk led to a reduction in evoked responses that was not linear function of the effect of stimulation of that trunk. In contrast, chronic removal caused a relative increase in evoked responses that ws inversely related to the decrease caused by acute removal. The implications of total functional overlap and neuromuscular reorganisation after chronic vagotomy are discussed. PMID:7439800

Denervation suppresses gastric tumorigenesis

PubMed Central

Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B.; Andersen, Gøran T.; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A.; Renz, Bernhard W.; Sandvik, Arne K.; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D.; Kaneko, Kazuhiro; Fox, James G.; Wang, Timothy C.; Chen, Duan

2015-01-01

The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor–mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and adult rats.

PubMed

Barella, Luiz F; Miranda, Rosiane A; Franco, Claudinéia C S; Alves, Vander S; Malta, Ananda; Ribeiro, Tatiane A S; Gravena, Clarice; Mathias, Paulo C F; de Oliveira, Júlio C

2015-01-01

What is the central question of this study? Different nerve contributes periods of life are known for their differential sensitivity to interventions, and increased parasympathetic activity affects the development and maintenance of obesity. Thus, we evaluated the involvement of the vagus nerve by performing a vagotomy in young or adult rats that were offered an obesogenic high-fat diet. What is the main finding and its importance? Although the accumulation of adipose tissue decreased in both younger and older groups, the younger rats showed a greater response to the effects of vagotomy in general. In addition to the important role of the parasympathetic activity, we suggest that the vagus nerve contributes to the condition of obesity. Obesity has become a global problem, and this condition develops primarily because of an imbalance between energy intake and expenditure. The high complexity involved in the regulation of energy metabolism results from several factors besides endocrine factors. It has been suggested that obesity could be caused by an imbalance in the autonomous nervous system, which could lead to a condition of high parasympathetic activity in counterpart to low sympathetic tonus. High-fat (HF) diets have been used to induce obesity in experimental animals, and their use in animals leads to insulin resistance, hyperinsulinaemia and high parasympathetic activity, among other disorders. The aim of this work was to evaluate the effects of a vagotomy performed at the initiation of a HF diet at two different stages of life, weaning and adulthood. The vagotomy reduced parasympathetic activity (-32 and -51% in normal fat-fed rats and -43 and -55% in HF diet-fed rats; P < 0.05) and fat depots (-17 and -33%, only in HF diet-fed rats; P < 0.05). High-fat diet-fed rats exhibited fasting hyperinsulinaemia (fivefold higher in young rats and threefold higher in older rats; P < 0.05); however, vagotomy corrected it in younger rats only, and a similar effect was

Neutrophil Recruitment and Articular Hyperalgesia in Antigen-Induced Arthritis are Modulated by the Cholinergic Anti-Inflammatory Pathway.

PubMed

Kanashiro, Alexandre; Talbot, Jhimmy; Peres, Raphael S; Pinto, Larissa G; Bassi, Gabriel S; Cunha, Thiago M; Cunha, Fernando Q

2016-11-01

The cholinergic anti-inflammatory pathway (CAP) is a complex neuroimmune mechanism triggered by the central nervous system to regulate peripheral inflammatory responses. Understanding the role of CAP in the pathogenesis of rheumatoid arthritis (RA) could help develop new therapeutic strategies for this disease. Therefore, we investigated the participation of this neuroimmune pathway on the progression of experimental arthritis. Using antigen-induced arthritis (AIA) model, we investigated in mice the effects of vagotomy or the pharmacological treatments with hexamethonium (peripheral nicotinic receptor antagonist), methylatropine (peripheral muscarinic receptor antagonist) or neostigmine (peripheral acetylcholinesterase inhibitor) on AIA progression. Unilateral cervical vagotomy was performed 1 week before the immunization protocol with methylated bovine serum albumin (mBSA), while drug administration was conducted during the period of immunization. On day 21, 6 hr after the challenge with mBSA injection in the femur-tibial joint, the local neutrophil migration and articular mechanical hyperalgesia were assessed. Herein, we observed that vagotomy or blockade of peripheral nicotinic (but not muscarinic) receptors exacerbated the clinical parameters of this disease. Moreover, peripheral acetylcholinesterase inhibition by neostigmine treatment promoted a reduction of neutrophil recruitment in the knee joint and articular hyperalgesia. Our results demonstrated that peripheral activation of CAP modulates experimental arthritis, providing a pre-clinical evidence of a potential therapeutic strategy for RA. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model.

PubMed

Koopman, F A; Vosters, J L; Roescher, N; Broekstra, N; Tak, P P; Vervoordeldonk, M J

2015-10-01

Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's syndrome and type 1 diabetes. The alpha-7 nicotinic acetylcholine receptor (α7nAChR) was stimulated with AR-R17779 or nicotine in NOD mice. In a second study, unilateral cervical vagotomy was performed. α7nAChR expression, focus scores, and salivary flow were evaluated in salivary glands (SG) and insulitis score in the pancreas. Cytokines were measured in serum and SG. α7nAChR was expressed on myoepithelial cells in SG. Monocyte chemotactic protein-1 levels were reduced in SG after AR-R17779 treatment and tumor necrosis factor production was increased in the SG of the vagotomy group compared to controls. Focus score and salivary flow were unaffected. NOD mice developed diabetes more rapidly after vagotomy, but at completion of the study there were no statistically significant differences in number of mice that developed diabetes or in insulitis scores. Intervention of the CAP in NOD mice leads to minimal changes in inflammatory cytokines, but did not affect overall inflammation and function of SG or development of diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit.

PubMed

Delpierre, S; Pugnat, C; Duté, N; Jammes, Y

1995-02-15

It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition.

Are the islets of Langerhans neuro-paraneuronal control centers of the exocrine pancreas?

PubMed

Radke, R; Stach, W

1986-10-01

The authors investigate whether the islets of Langerhans can actually be regarded as "neuro-paraneuronal control centers of the exocrine pancreas" as was first suggested by Fujita and Kobayashi (1979). The question is discussed on the basis of the authors' electron microscopic findings regarding pancreatic innervation before and after truncular vagotomy. The results do not seem to support the above hypothesis which advocates that the intrainsular axons are principally engaged in the release of their transmitters into the capillaries in order to regulate, via the insuloacinar portal vessels, the exocrine function of the pancreas. On the contrary, the present data draw attention to the unambiguous assignation of intrainsular axons to endocrine cells, a point of question in line with several findings published in the literature including papers by the first supporters of this hypothesis. No change was observed in the innervation pattern of the effector cells after vagotomy.

Activated cranial cervical cord neurons affect left ventricular infarct size and the potential for sudden cardiac death

PubMed Central

Southerland, E. Marie; Gibbons, David D.; Smith, S. Brooks; Sipe, Adam; Williams, Carole Ann; Beaumont, Eric; Armour, J. Andrew; Foreman, Robert D.; Ardell, Jeffrey L.

2012-01-01

To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30 min of LAD coronary arterial occlusion (CAO) were studied 3 hours after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50 Hz; 0.2 ms; 90% of motor threshold, starting 15 min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis. PMID:22502863

The effect of vagal afferent on total vascular compliance in rats.

PubMed

Kinoshita, T

1993-04-01

This study was designed to investigate the effect of vagal afferent stimulation on total vascular compliance (TVC). Rats were anesthetized with sodium pentobarbital and artificially ventilated, TVC was determined together with stressed and unstressed blood volumes by measuring mean circulatory filling pressure (Pmcf) at three different levels of circulating blood volume. Measurements was repeated with the intact vagus, after vagotomy and during stimulation of vagal afferents. Vagotomy caused no change in TVC, Pmcf, and stressed and unstressed blood volumes. On the other hand, electrical stimulation of the vagal afferents for 30 sec increased TVC from 3.03 +/- 0.51 to 3.39 +/- 0.44 ml.mmHg(-1).kg(-1) (P < 0.05) and decreased Pmcf from 7.83 +/- 1.40 to 7.22 +/- 1.21 mmHg (P < 0.05). Neither stressed nor unstressed blood volume was changed by vagal stimulation. These results indicate that excitation of vagal afferent causes venodilation and increases TVC without changing stressed and unstressed blood volumes.

Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge

PubMed Central

Schelegle, Edward S.; Walby, William F.

2012-01-01

Brown-Norway rats (n = 113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O3) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0 ppm O3 for 8 hours. There were three groups: 1) control; 2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and 3) vagotomy. O3 inhalation resulted in a significant increase in lung resistance (RL) and an exaggerated response to subsequent allergen challenge. PCT abolished the O3-induced increase in RL and significantly reduced the increase in RL induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O3 inhalation and subsequent challenge with allergen. In this model of O3 exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. PMID:22525484

76 FR 39159 - Schedule for Rating Disabilities; The Digestive System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... commenter suggested that we evaluate gastrectomy and vagotomy- pyloroplasty under the same criteria. The... in order to evaluate it. This material is unnecessary, since there are separate diagnostic codes for....113. We propose to direct the rater to separately evaluate two or more conditions in Sec. 4.114 only...

Differential Activation of Pontomedullary Nuclei by Acid Perfusion of Different Regions of the Esophagus

PubMed Central

Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

2010-01-01

The objective of this study was to determine the brain stem nuclei and physiological responses activated by esophageal acidification. The effects of perfusion of the cervical (ESOc), or thoracic (ESOt) esophagus with PBS or HCl on c-fos immunoreactivity of the brain stem or on physiological variables, and the effects of vagotomy were examined in anesthetized cats. We found that acidification of the ESOc increased the number of c-fos positive neurons in the area postrema (AP), vestibular nucleus (VN), parabrachial nucleus (PBN), nucleus ambiguus (NA), dorsal motor nucleus (DMN), and all subnuclei of the nucleus tractus solitarius (NTS), but one. Acidification of the ESOt activated neurons in the central (CE), caudal (CD), dorsomedial (DM), dorsolateral (DL), ventromedial (VM) subnuclei of NTS, and the DMN. Vagotomy blocked all c-fos responses to acid perfusion of the whole esophagus (ESOw). Perfusion of the ESOc or ESOt with PBS activated secondary peristalsis (2P), but had no effect on blood pressure, heart rate, or respiratory rate. Perfusion of the ESOc, but not ESOt, with HCL activated pharyngeal swallowing (PS), profuse salivation, or physiological correlates of emesis. Vagotomy blocked all physiological effects of ESOw perfusion. We conclude that acidification of the ESOc and ESOt activate different sets of pontomedullary nuclei and different physiological responses. The NTSce, NTScom, NTSdm, and DMN are associated with activation of 2P, the NTSim and NTSis, are associated with activation of PS, and the AP, VN, and PBN are associated with activation of emesis and perhaps nausea. All responses to esophageal fluid perfusion or acidification are mediated by the vagus nerves. PMID:20655885

Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

PubMed Central

Meyers, Kelly; Lim, Audrey; Dye, Matthew; Pak, Diana; Rinaman, Linda; Yates, Bill J.

2014-01-01

Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew. PMID:24430885

Medical versus surgical treatment for refractory or recurrent peptic ulcer.

PubMed

Gurusamy, Kurinchi Selvan; Pallari, Elena

2016-03-29

authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality). We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the

Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.; Landauer, M.R.

1990-06-01

The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated thatmore » BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways.« less

Capsaicin and regulation of respiration: interaction with central substance P mechanisms.

PubMed

Hedner, J; Hedner, T; Jonason, J

1985-01-01

The neuropharmacological effects of capsaicin (CAPS) (8-methyl-N-vanillyl-6-nonenamide) have been closely linked to the peptide neurotransmitter substance P (SP). In order to elucidate SP mechanisms in peripheral and central control of breathing we have studied the respiratory effects of CAPS and SP administration to neonatal and adult rats using a whole body plethysmographic method. CAPS (3 and 30 micrograms) induced an immediate apnea after intravenous injection. This effect could be reduced by vagotomy but not further changed by combined vagotomy and glossopharyngectomy. The apnoic periods were followed by periods of tachypnea. Intracerebroventricular (i.c.v.) administration of CAPS resulted in an increased tidal volume (VT) and a decreased respiratory frequency (f), i.e. a respiratory response similar to that seen after i.c.v. SP. No apnoic episodes were seen after i.c.v. injection. The respiratory pattern after acute i.c.v. CAPS administration was not significantly changed by neonatal CAPS pretreatment. However, while saline pretreated control animals responded to an i.c.v. injection of SP with an increase in VT and inspiratory drive (VT/TI), animals pretreated with CAPS responded with a shortening of inspiratory and expiratory time in combination with an increase in VT. Similar changes have been observed in vagotomized animals after SP administration. It is concluded that CAPS elicits apnea via mechanisms located outside the CNS, which cannot be fully deafferented by combined vagotomy and glossopharyngectomy. Furthermore, CAPS i.c.v. induces a stimulation of respiration by a central mechanism of action, possibly due to a release of SP. Neonatal pretreatment with CAPS modifies the respiratory response to i.c.v. SP. This effect might be due to an impairment in tonical afferent SP mechanisms to the central respiratory regulating system and possibly also to an impairment of central SP mechanisms involved in respiration.

Treatment of hemorrhagic gastritis by antacid.

PubMed

Simonian, S J; Curtis, L E

1976-10-01

A simple and safe method of nonsurgical treatment for the control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrocloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleeding had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89% control of hemorrhage compare favorably with those in the literature.

Treatment of hemorrhagic gastritis by antacid.

PubMed Central

Simonian, S J; Curtis, L E

1976-01-01

A simple and safe method of nonsurgical treatment for the control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrocloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleeding had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89% control of hemorrhage compare favorably with those in the literature. PMID:13746

Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge.

PubMed

Schelegle, Edward S; Walby, William F

2012-05-31

Brown-Norway rats (n=113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O(3)) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0ppm O(3) for 8h. There were three groups: (1) control; (2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and (3) vagotomy. O(3) inhalation resulted in a significant increase in lung resistance (R(L)) and an exaggerated response to subsequent allergen challenge. PCT abolished the O(3)-induced increase in R(L) and significantly reduced the increase in R(L) induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O(3) inhalation and subsequent challenge with allergen. In this model of O(3) exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. Copyright © 2012 Elsevier B.V. All rights reserved.

[The choice of resection volume by the combination of perforative duodenal ulcer with other complications of the ulcer disease].

PubMed

Vachev, A N; Korytsev, V K; Antropov, I V

2013-01-01

Treatment results of 59 patients with the complicated ulcer disease were analyzed. Authors prove, that in cases of perforative duodenal ulcer, the operation should aim the treatment of all the complications. The use of 2/3 gaster resection in combination with Jadd pyloroplasty and trunk vagotomy led to the decrease of the lethality rate on 21%.

Reflex changes in breathing pattern evoked by inhalation of wood smoke in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Y.R.; Lai, C.J.

1994-06-01

The acute ventilatory response to inhalation of wood smoke was studied in 58 anesthetized Sprague-Dawley rats. Wood smoke ([approximately]6 ml) was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, either a slowing of respiration (SR) (n=39) or an augmented inspiration (AI) (n=19) was elicited consistently in each rat. The SR was primarily due to a prolongation of expiratory duration, whereas the AI was characterized by a two-step inspiratory flow leading to an exceedingly large tidal volume. Both initial responses, usually accompanied by bradycardia and hypotension, were reduced by inhaling smoke at a decreased concentration.more » After these initial responses, a delayed tachypnea developed and reached its peak 6-10 breaths after inhalation of smoke. Both the SR and AI were completely abolished by bilateral cervical vagotomy. In contrast, the delayed tachypneic response was not prevented by vagotomy but was significantly attenuated by denervation of peripheral chemoreceptors. The authors conclude that the initial responses to inhalation of several tidal breaths of wood smoke are mediated through vagal bronchopulmonary afferents, whereas the delayed tachypnea may involve nonvagal mechanisms that include a stimulation of peripheral chemoreceptors.« less

Lung reflexes in rabbits during pulmonary stretch receptor block by sulphur dioxide.

PubMed

Davies, A; Dixon, M; Callanan, D; Huszczuk, A; Widdicombe, J G; Wise, J C

1978-07-01

Anaesthetized rabbits were given 200 ppm sulphur dioxide to breathe for 10 min. This abolished activity in 23 of 26 pulmonary stretch receptors, while leaving that of lung irritant receptors unimpaired. The Breuer-Hering reflex was abolished and breathing became deeper and slower. Inspiratory time (tI) was increased and expiratory time (tE) decreased. Subsequent vagotomy increased tidal volume (VT), tI and tE. In animals with stretch receptors blocked, injections of phenyl diguanide and histamine still increased breathing frequency and decreased VT, indicating that reflexes from lung irritant and J-receptors were intact. Inhalation of 8% CO2 caused a bigger increase in frequency and tidal volume in rabbits with stretch receptor block compared with controls or those after vagotomy. Induction of pneumothorax with stretch receptor block transiently prolonged tI and shortened tE; removal of the pneumothorax also transiently shortened tE and usually also decreased tI. The results suggest that lung irritant receptors reflexly shorten tE in all our experimental conditions, but have various effects on tI which may depend on the timing of the irritant receptor discharge and refractoriness of the inspiratory response.

Reflex control of discharge in motor fibres to the larynx

PubMed Central

Głogowska, Maria; Stransky, A.; Widdicombe, J. G.

1974-01-01

1. Action potentials have been recorded from single laryngeal motor fibres, with expiratory or inspiratory phases, in cats anaesthetized with pentobarbitone and breathing through a tracheal cannula. 2. Pneumothorax increased the discharge of both inspiratory and expiratory units, the inspiratory response being greatly reduced by bilateral vagotomy below the origin of the recurrent laryngeal nerves. 3. Addition of a `viscous' resistance to breathing, or asphyxial rebreathing through an added dead space, increased the activity of inspiratory units and decreased that of expiratory units. 4. Induction of pulmonary oedema decreased the discharge of inspiratory units and increased that of expiratory units. After vagotomy the response of inspiratory units was reversed. 5. Intravenous injections of potassium cyanide increased the activity of both types of unit. 6. Chemical irritation of the laryngeal mucosa decreased the discharge of inspiratory units and increased that of expiratory units, whether the vagi were intact or cut. 7. It is concluded that expiratory unit discharge can be correlated with expiratory laryngeal resistance, but that inspiratory unit discharge does not correlate so well with inspiratory laryngeal resistance. 8. The relationship between laryngeal motor-fibre activity and the contractions of the inspiratory and expiratory muscles of breathing is discussed. PMID:4415512

Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.

PubMed

Kanamori, Hiroyuki; Nakade, Yukiomi; Yamauchi, Taeko; Sakamoto, Kazumasa; Inoue, Tadahisa; Yamamoto, Takaya; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sumida, Yoshio; Nakao, Haruhisa; Fukuzawa, Yoshitaka; Yoneda, Masashi

2017-01-01

Nicotine, a major compound in cigarette smoke, decreases food intake and body weight gain in mammals; however, the influence of nicotine on the progression of non-alcoholic steatohepatitis (NASH) remains controversial. This study aimed to investigate the effect of nicotine on NASH in rat models. Male Wistar rats were fed choline-deficient, l-amino acid-defined (CDAA) diet and treated with nicotine or saline. Food intake, body weight gain, presence of hepatic steatosis, inflammation, and fibrosis were assessed 6 weeks after the rats were fed CDAA diet. Hepatic branch vagotomy was performed to elucidate the mechanism through which nicotine affected steatohepatitis. CDAA diet induced hepatic steatosis, inflammation, and fibrosis, as well as increased the expression of inflammation-related genes. Conversely, nicotine significantly attenuated food intake, body weight gain, and inhibited the CDAA-diet-induced hepatic steatosis, inflammation, and fibrosis, together with increased expression of inflammation-related genes. Hepatic branch vagotomy by itself decreased food intake, body weight gain, and attenuated the CDAA-diet-induced hepatic steatosis, but not inflammation. However, nicotine did not change the food intake, body weight gain, and CDAA diet-induced hepatic steatosis and inflammation in vagotomized rats. These results suggest that nicotine attenuates the CDAA-diet-induced hepatic steatosis and inflammation through the hepatic branch of the vagus nerve in rats.

Clinical and laboratory study of postvagotomy diarrhoea

PubMed Central

Browning, G. G.; Buchan, K. A.; Mackay, C.

1974-01-01

Thirty-two patients with diarrhoea, on average four years following truncal vagotomy and drainage, were studied. A comparison was made with 24 patients without postvagotomy diarrhoea. The incidence of bacterial colonization of the upper small intestine was no different in the two groups, though patients with a gastroenterostomy had a significantly higher incidence than those with a pyloroplasty. There was a higher incidence of `anaerobic colonization' in patients with diarrhoea, but statistical significance was not reached. Colonization was associated with significantly lower levels of gastric acid secretion. Though 13 patients with diarrhoea had an abnormal faecal fat excretion, no correlation could be found between this and the severity of the diarrhoea or bacterial colonization, either with an anaerobic or a coliform type flora. In patients with diarrhoea, no small intestinal mucosal abnormality was detected, the mean haematological and serum biochemistry values were within normal limits, and the body weight was similar to that before operation. Two patients with diarrhoea had abnormal haematological values five years following vagotomy and gastroenterostomy in association with `anaerobic colonization' of the upper small intestine. As the incidence of haematological abnormalities after gastric surgery increases with time, colonized patients might merit particularly close clinical observation. PMID:4608280

Dietary 2’-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents

PubMed Central

Vazquez, Enrique; Barranco, Alejandro; Ramirez, Maria; Gruart, Agnes; Delgado-Garcia, Jose M.; Jimenez, Maria L.; Buck, Rachael; Rueda, Ricardo

2016-01-01

2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits. PMID:27851789

[Supra-vaterian duodenal ulcer perforated into the transverse colon. Severe state of cachexia].

PubMed

Ionescu, A; Moisa, V; Sciuca, S; Hamburda, M

1976-01-01

In connection with a clinical observation the authors refer on this rare complication of duodenal ulcer situated above the Vater ampula. Fistulization in the transverse colon led to a short-circulting of the small bowel and an advanced cachectic condition. Surgery consisted in the suppression of the fistula that had developed between the duodenum and the colon, associated with anterior duodeno-papillo-antrectomy, Judo piloroplastia and bilateral, sub-diaphragmatic troncular vagotomy, and resulted in the recovery of the patient.

Arterial gastroduodenal infusion of cholecystokinin-33 stimulates the exocrine pancreatic enzyme release via an enteropancreatic reflex, without affecting the endocrine insulin secretion in pigs.

PubMed

Rengman, Sofia; Weström, Björn; Ahrén, Bo; Pierzynowski, Stefan G

2009-03-01

Cholecystokinin (CCK)-dependent exocrine pancreatic regulation seems to involve different pathways in different species. The aims were to explore the enteropancreatic reflex in the CCK-mediated regulation of the exocrine pancreas and to evaluate a possible involvement of this reflex in the endocrine insulin release. In anesthetized pigs, CCK-33 in increasing doses (4-130 pmol kg 10 min) was infused locally to the gastroduodenal artery, or systemically via the jugular vein. Also, a low CCK-33 dose (13 pmol kg) was injected to the duodenum/antrum area before and after a bilateral truncal vagotomy. Cholecystokinin-33 in the physiological dose range 4 to 32 pmol kg 10 min increased protein and trypsin outputs after local infusion to the antral-duodenal area, whereas it had no effect after systemic infusion. Cholecystokinin-33 in the pharmacological dose range 64 to 130 pmol kg 10 min further increased the secretion after both local and systemic infusions. Only CCK-33 infusions in the pharmacological dose range were able to elevate the plasma insulin levels. Vagotomy had no effect on CCK-33-mediated stimulation of the enzyme release, whereas it had a significant effect on the plasma insulin level. Cholecystokinin-33 in the physiological dose range 4 to 32 pmol kg 10 min stimulates the enzyme secretion but had no effect on the insulin release via a short enteropancreatic pathway in pigs.

Potential of intestinal electrical stimulation for obesity: a preliminary canine study.

PubMed

Yin, Jieyun; Ouyang, Hui; Chen, Jiande D Z

2007-05-01

The aims of this study were to investigate the therapeutic potential of intestinal electrical stimulation (IES) for obesity. Experiments were performed to investigate the effects of IES on food intake, gastric tone, gastric accommodation, and its possible pathway. Ten normal dogs and six dogs with truncal vagotomy were used in this study. Each dog was equipped with a gastric cannula for the measurement of gastric tone and accommodation by barostat and one pair of duodenal serosal electrodes for IES. The experiment on food intake was composed of both control session without IES and IES session after a 28-hour fast. The experiment on gastric tone and accommodation was performed in the fasting and fed states and composed of three sessions: control, IES, and IES with N(G)-nitro-l-arginine. IES significantly reduced food intake in the normal dogs (459.0 vs. 312.6 grams, p < 0.001). The food intake was negatively correlated with the fasting gastric volume during IES. IES significantly decreased fasting gastric tone in the normal dogs reflected as a decrease in gastric volume (89.1 vs. 261.3 mL, p < 0.01), which was abolished by vagotomy and N(G)-nitro-l-arginine. IES reduces food intake and inhibits gastric tone in the fasting state. The inhibitory effect of IES on gastric tone is mediated by both vagal and nitrergic pathway.

Chronic Deep Brain Stimulation of the Hypothalamic Nucleus in Wistar Rats Alters Circulatory Levels of Corticosterone and Proinflammatory Cytokines

PubMed Central

Calleja-Castillo, Juan Manuel; De La Cruz-Aguilera, Dora Luz; Manjarrez, Joaquín; Velasco-Velázquez, Marco Antonio; Morales-Espinoza, Gabriel; Moreno-Aguilar, Julia; Hernández, Maria Eugenia; Aguirre-Cruz, Lucinda

2013-01-01

Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-α (120%; P < 0.01) and IFN-γ (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1β (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication. PMID:24235973

Perforated peptic ulcer disease: mid-term outcome among Iranian population.

PubMed

Kamani, Freshteh; Moghimi, Mehrdad; Marashi, Seyed Ali; Peyrovi, Habibollah; Sheikhvatan, Mehrdad

2010-06-01

The aim of this study was to evaluate midterm outcome of patients with perforated peptic ulcer disease and to determine the main predictors of mid-term mortality. Demographic and clinical characteristics of 56 patients with the diagnosis of perforated peptic ulcer who were hospitalized in Taleghani Hospital over a 10-year period (19962005) were retrospectively collected, and in-hospital mortality and morbidity were determined. Patients were also followed for one month, one year and five years after the operation. Among these patients, 85.5% were treated with omental patch closure, 7.1% underwent vagotomy pyloroplasty, 5.3% underwent concurrent vagotomy and gastrojejunostomy, and 1.8% underwent antrectomy. In-hospital mortality and morbidity were 5.3% and 48.2%, respectively. Survival rates at one month, one year and five years after the operation were 92.9%, 89.3% and 78.6%, respectively. Advanced age (p=0.001), preoperative shock (p=0.003), history of malignancy before surgery (p=0.001), treatment delay (p=0.028), intensive care unit admission (p=0.032), and size of ulcer >5 cm (p=0.043) were the main predictors of five-year mortality in the followed patients. Mid-term mortality of treated perforated peptic ulcer disease among our population was notable, and the main predictors of mortality included advanced age, history of malignancy, treatment delay, intensive care unit admission, and ulcer size.

Stress Ulcer Disease in the Burned Patient

DTIC Science & Technology

1981-03-01

8 ia o World J. Sunt. 5, 209.222, 1981 o Wurkl Journal (rf Skirgpry /■’ Stress Ulcer Disease in the Burned Patient Basil A.\\Priiitt.Jr.yM.D...andCleon W.^oodwin, Jr|. M.D. U.S. Army Institute ofSurgical Research. Brooke Army Medical Center. Fort Sam Houston. Stress -induced ulcers of the...has occurred, these compli- cations of Curling’s ulcer appear to be best treated by gas- tric resection combined with vagotomy. The stress caused hy

[Selective proximal vagotomy in duodenal ulcer complicated by decompensated pyloroduodenal stenosis].

PubMed

Saenko, V F; Pustovit, A A; Shchitov, A V

1999-01-01

The result of surgical treatment of 281 patient with duodenal ulcer disease, complicated by decompensated pyloroduodenal stenosis, was presented. Analysis of compensational possibilities of stomach motility and application of elaborated method of diagnosis and preoperative preparation have permitted to perform in 243 (86.6%) of patients the organ-preserving operation. Operative interventions of resectional type are done in 38 (13.4%) of the patients. Late follow-up result of treatment was studied up in 172 patients in terms from 1 year to 5 years. Postresectional syndrome have occurred in 15 (8.5%), recurrency--in 10 (6%) of patients. Mortality was 1.2%.

GLP-1 Elicits an Intrinsic Gut-Liver Metabolic Signal to Ameliorate Diet-Induced VLDL Overproduction and Insulin Resistance.

PubMed

Khound, Rituraj; Taher, Jennifer; Baker, Christopher; Adeli, Khosrow; Su, Qiaozhu

2017-12-01

Perturbations in hepatic lipid and very-low-density lipoprotein (VLDL) metabolism are involved in the pathogenesis of obesity and hepatic insulin resistance. The objective of this study is to delineate the mechanism of subdiaphragmatic vagotomy in preventing obesity, hyperlipidemia, and insulin resistance. By subjecting the complete subdiaphragmatic vagotomized mice to various nutritional conditions and investigating hepatic de novo lipogenesis pathway, we found that complete disruption of subdiaphragmatic vagal signaling resulted in a significant decrease of circulating VLDL-triglyceride compared with the mice obtained sham procedure. Vagotomy further prevented overproduction of VLDL-triglyceride induced by an acute fat load and a high-fat diet-induced obesity, hyperlipidemia, hepatic steatosis, and glucose intolerance. Mechanistic studies revealed that plasma glucagon-like peptide-1 was significantly raised in the vagotomized mice, which was associated with significant reductions in mRNA and protein expression of SREBP-1c (sterol regulatory element-binding protein 1c), SCD-1 (stearoyl-CoA desaturase-1), and FASN (fatty acid synthase), as well as enhanced hepatic insulin sensitivity. In vitro, treating mouse primary hepatocytes with a glucagon-like peptide-1 receptor agonist, exendin-4, for 48 hours inhibited free fatty acid, palmitic acid treatment induced de novo lipid synthesis, and VLDL secretion from hepatocytes. Elevation of glucagon-like peptide-1 in vagotomized mice may prevent VLDL overproduction and insulin resistance induced by high-fat diet. These novel findings, for the first time, delineate an intrinsic gut-liver regulatory circuit that is mediated by glucagon-like peptide-1 in regulating hepatic energy metabolism. © 2017 American Heart Association, Inc.

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

PubMed

Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang

2013-01-15

Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

Neural mechanisms and delayed gastric emptying of liquid induced through acute myocardial infarction in rats.

PubMed

Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de

2015-02-01

In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1 mA/10 s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Importance of brain-gut axis in the gastroprotection induced by gastric and remote preconditioning.

PubMed

Brzozowski, T; Konturek, P C; Pajdo, R; Kwiecień, S; Sliwowski, Z; Drozdowicz, D; Ptak-Belowska, A; Pawlik, M; Konturek, S J; Pawlik, W W; Hahn, G G

2004-03-01

Limitation of the damage to the organs such as heart, liver, intestine, stomach and brain by an earlier brief complete occlusion of their arteries is defined as ischemic preconditioning (IP). No study so for has been undertaken to check whether brain-gut axis is involved in the gastroprotection exhibited by gastric IP or in that induced by repeated brief episodes of ischemia of remote organs such as heart and liver. This study was designed to determine the possible involvement of vagal and sensory afferent nerves, in the mechanism of gastric and remote organ IP on the gastric mucosa in rats exposed to prolonged ischemia-reperfusion with or without functional ablation of sensory nerves by capsaicin or in those with removed vagal innervation by vagotomy. This gastric IP was induced by short ischemia episodes (occlusion of celiac artery 1-5 times for 5 min) applied 30 min before subsequent ischemia followed by 3 h of reperfusion (I/R) and compared with remote IP induced by occlusion of left descending coronary artery or hepatic artery plus portal vein. The area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured by H(2)-gas clearance method and mucosal biopsy samples were taken for the assessment of calcitonin gene-related peptide (CGRP) by RIA. Exposure of gastric mucosa to standard 3 h of I/R produced numerous gastric lesions and significant fall in the GBF and mucosal CGRP content. Two 5 min short ischemic episodes by occlusion of coronary or hepatic arteries, significantly reduced gastric damage induced by I/R with the extent similar to that exhibited by two short (5 min) episodes of gastric ischemia. These protective effects of gastric and remote IPs were accompanied by a restoration of the fall in the CGRP content caused by I/R alone. Protection and hyperemia induced by gastric IP were significantly attenuated in capsaicin-denervated or vagotomized animals and completely removed in those exposed to the combination of vagotomy

Vagotomy Reverses Established Allergen-Induced Airway Hyperreactivity to Methacholine in the Mouse

EPA Science Inventory

We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate ma...

Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

PubMed

Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

2010-12-01

Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

Vagal-dependent nonlinear variability in the respiratory pattern of anesthetized, spontaneously breathing rats

PubMed Central

Dhingra, R. R.; Jacono, F. J.; Fishman, M.; Loparo, K. A.; Rybak, I. A.

2011-01-01

Physiological rhythms, including respiration, exhibit endogenous variability associated with health, and deviations from this are associated with disease. Specific changes in the linear and nonlinear sources of breathing variability have not been investigated. In this study, we used information theory-based techniques, combined with surrogate data testing, to quantify and characterize the vagal-dependent nonlinear pattern variability in urethane-anesthetized, spontaneously breathing adult rats. Surrogate data sets preserved the amplitude distribution and linear correlations of the original data set, but nonlinear correlation structure in the data was removed. Differences in mutual information and sample entropy between original and surrogate data sets indicated the presence of deterministic nonlinear or stochastic non-Gaussian variability. With vagi intact (n = 11), the respiratory cycle exhibited significant nonlinear behavior in templates of points separated by time delays ranging from one sample to one cycle length. After vagotomy (n = 6), even though nonlinear variability was reduced significantly, nonlinear properties were still evident at various time delays. Nonlinear deterministic variability did not change further after subsequent bilateral microinjection of MK-801, an N-methyl-d-aspartate receptor antagonist, in the Kölliker-Fuse nuclei. Reversing the sequence (n = 5), blocking N-methyl-d-aspartate receptors bilaterally in the dorsolateral pons significantly decreased nonlinear variability in the respiratory pattern, even with the vagi intact, and subsequent vagotomy did not change nonlinear variability. Thus both vagal and dorsolateral pontine influences contribute to nonlinear respiratory pattern variability. Furthermore, breathing dynamics of the intact system are mutually dependent on vagal and pontine sources of nonlinear complexity. Understanding the structure and modulation of variability provides insight into disease effects on respiratory

[Gas embolism in the rat].

PubMed

Lagneaux, D; Bodson, L; Remacle, R

1982-11-01

Gaseous carbon dioxide was used to produce experimental pulmonary embolism in anaesthetized rats, the vagal nerves of which were either intact or severed. 1. Within seconds following intravenous CO2 injection, pulmonary hypertension, moderate systemic hypotension and bradycardia occurred. After a short hyperventilation period, intact rats showed a brief and transient apnea. Vagotomy suppresses (1) apnea presumably by interruption of reflexes from J pulmonary receptors (Paintal, 1967) and (2) bradycardia by the same token or by suppression of a reflex from auricular origin (Thorén, 1976). 2. Following that initial phase, the events were totally dependent on the right ventricular ability to overcome the pulmonary vascular resistance. If it failed, left and right pressures fell and a secondary apnea followed systemic hypotension. Vagotomy had no effect at this stage. Only half of all animals showed these features. 3. Pulmonary hypertension and hyperventilation lasted twenty minutes at least in intact rats, while vagotomized ones showed an evolution toward acute pulmonary oedema and death. 4. With the same amount of CO2/kg, the dogs of Verstappen et al. (1977) showed only minimal cardio-vascular alterations. The mode of effective embolization in the two species was probably different, as a function of the respective circulation times. But this geometrical point of view is not the only one to be considered: in rats, the rise of pulmonary arterial blood pressure remains even when mechanical obstruction by bubbles has dissipated and a local prolonged vasospasm could be advocated. 5. Acute pulmonary oedema rapidly occurring in vagotomized rats seems to be related to the hyperinflation (very large tidal volume) as also seen in this species with other intensive respiratory drives.

Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats

PubMed Central

Kirkup, Anthony J; Jiang, Wen; Bunnett, Nigel W; Grundy, David

2003-01-01

Proteinase-activated receptor 2 (PAR2) is a receptor for mast cell tryptase and trypsins and might participate in brain-gut communication. However, evidence that PAR2 activation can lead to afferent impulse generation is lacking. To address this issue, we examined the sensitivity of jejunal afferent nerves to a hexapeptide agonist of PAR2, SLIGRL-NH2, and the modulation of the resulting response to treatment with drugs and vagotomy. Multiunit recordings of jejunal afferent activity were made using extracellular recording techniques in anaesthetised male rats. SLIGRL-NH2 (0.001–1 mg kg−1, I.V.) increased jejunal afferent firing and intrajejunal pressure. The reverse peptide sequence (1 mg kg−1, I.V.), which does not stimulate PAR2, was inactive. Naproxen (10 mg kg−1, I.V.), but not a cocktail of ω-conotoxins GVIA and SVIB (each at 25 μg kg−1, I.V.), curtailed both the afferent response and the intrajejunal pressure rise elicited by the PAR2 agonist. Although neither treatment modulated the peak magnitude of the afferent firing, they each altered the intestinal motor response, unmasking an initial inhibitory component. Nifedipine (1 mg kg−1, I.V.) reduced the peak magnitude of the afferent nerve discharge and abolished the initial rise in intrajejunal pressure produced by SLIGRL-NH2. Vagotomy did not significantly influence the magnitude of the afferent response to the PAR2 agonist, which involves a contribution from capsaicin-sensitive fibres. In conclusion, intravenous administration of SLIGRL-NH2 evokes complex activation of predominantly spinally projecting extrinsic intestinal afferent nerves, an effect that involves both direct and indirect mechanisms. PMID:14561839

Surgery for gastrinoma.

PubMed

Cisco, Robin M; Norton, Jeffrey A

2007-01-01

Surgery has been demonstrated to offer potential for cure in patients who have sporadic ZES and improved tumor-related survival in all patients who have ZES with gastrinomas larger than 2.5 cm. Techniques such as preoperative localization with SRS and intraoperative localization with duodenotomy have improved the effectiveness of surgical intervention for ZES. Future directions for investigation should include better defining the role of preoperative EUS and developing new, more sensitive techniques for preoperative localization. More research also is needed to define the appropriate indications for pancreaticoduodenectomy in ZES and to determine whether proximal vagotomy should be performed at the time of surgical exploration.

Activation of anorexigenic pro-opiomelanocortin neurones during refeeding is independent of vagal and brainstem inputs.

PubMed

Fekete, C; Zséli, G; Singru, P S; Kádár, A; Wittmann, G; Füzesi, T; El-Bermani, W; Lechan, R M

2012-11-01

After fasting, satiety is observed within 2 h after reintroducing food, accompanied by activation of anorexigenic, pro-opiomelanocortin (POMC)-synthesising neurones in the arcuate nucleus (ARC), indicative of the critical role that α-melanocyte-stimulating hormone has in the regulation of meal size during refeeding. To determine whether refeeding-induced activation of POMC neurones in the arcuate is dependent upon the vagus nerve and/or ascending brainstem pathways, bilateral subdiaphragmatic vagotomy or transection of the afferent brainstem input to one side of the ARC was performed. One day after vagotomy or 2 weeks after brain surgery, animals were fasted and then refed for 2 h. Sections containing the ARC from vagotomised animals or animals with effective transection were immunostained for c-Fos and POMC to detect refeeding-induced activation of POMC neurones. Quantitative analyses of double-labelled preparations demonstrated that sham-operated and vagotomised animals markedly increased the number of c-Fos-immunoreactive (-IR) POMC neurones with refeeding. Furthermore, transection of the ascending brainstem pathway had no effect on diminishing c-Fos-immunoreactivity in POMC neurones on either side of the ARC, although it did diminish activation in a separate, subpopulation of neurones in the dorsomedial posterior ARC (dmpARC) on the transected side. We conclude that inputs mediated via the vagus nerve and/or arising from the brainstem do not have a primary role in refeeding-induced activation of POMC neurones in the ARC, and propose that these neurones may be activated solely by direct effects of circulating hormones/metabolites during refeeding. Activation of the dmpARC by refeeding indicates a previously unrecognised role for these neurones in appetite regulation in the rat. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis-Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway.

PubMed

Zhai, Qian; Lai, Dengming; Cui, Ping; Zhou, Rui; Chen, Qixing; Hou, Jinchao; Su, Yunting; Pan, Libiao; Ye, Hui; Zhao, Jing-Wei; Fang, Xiangming

2017-10-01

Basal forebrain cholinergic neurons are proposed as a major neuromodulatory system in inflammatory modulation. However, the function of basal forebrain cholinergic neurons in sepsis is unknown, and the neural pathways underlying cholinergic anti-inflammation remain unexplored. Animal research. University research laboratory. Male wild-type C57BL/6 mice and ChAT-ChR2-EYFP (ChAT) transgenic mice. The cholinergic neuronal activity of the basal forebrain was manipulated optogenetically. Cecal ligation and puncture was produced to induce sepsis. Left cervical vagotomy and 6-hydroxydopamine injection to the spleen were used. Photostimulation of basal forebrain cholinergic neurons induced a significant decrease in the levels of tumor necrosis factor-α and interleukin-6 in the serum and spleen. When cecal ligation and puncture was combined with left cervical vagotomy in photostimulated ChAT mice, these reductions in tumor necrosis factor-α and interleukin-6 were partly reversed. Furthermore, photostimulating basal forebrain cholinergic neurons induced a large increase in c-Fos expression in the basal forebrain, the dorsal motor nucleus of the vagus, and the ventral part of the solitary nucleus. Among them, 35.2% were tyrosine hydroxylase positive neurons. Furthermore, chemical denervation showed that dopaminergic neurotransmission to the spleen is indispensable for the anti-inflammation. These results are the first to demonstrate that selectively activating basal forebrain cholinergic neurons is sufficient to attenuate systemic inflammation in sepsis. Specifically, photostimulation of basal forebrain cholinergic neurons activated dopaminergic neurons in dorsal motor nucleus of the vagus/ventral part of the solitary nucleus, and this dopaminergic efferent signal was further transmitted by the vagus nerve to the spleen. This cholinergic-to-dopaminergic neural circuitry, connecting central cholinergic neurons to the peripheral organ, might have mediated the anti

Electroacupuncture at LI11 promotes jejunal motility via the parasympathetic pathway.

PubMed

Hu, Xuanming; Yuan, Mengqian; Yin, Yin; Wang, Yidan; Li, Yuqin; Zhang, Na; Sun, Xueyi; Yu, Zhi; Xu, Bin

2017-06-21

Gastrointestinal motility disorder has been demonstrated to be regulated by acupuncture treatment. The mechanisms underlying the effects of acupuncture stimulation of abdominal and lower limb acupoints on gastrointestinal motility have been thoroughly studied; however, the physiology underlying the effects of acupuncture on the forelimbs to mediate gastrointestinal motility requires further exploration. The aim of this study was to determine whether electroacupuncture (EA) at LI11 promotes jejunal motility, whether the parasympathetic pathway participates in this effect, and if so, which somatic afferent nerve fibres are involved. A manometric balloon was used to observe jejunal motility. The effects and mechanisms of EA at LI11 were explored in male Sprague-Dawley rats with or without drug administration (propranolol, clenbuterol, acetylcholine, and atropine) and with or without vagotomy. Three types of male mice (β 1 β 2 receptor-knockout [β 1 β 2 -/- ] mice, M 2 M 3 receptor-knockout [M 2 M 3 -/- ] mice and wild-type [WT] mice) were also studied by using different EA intensities (1, 2, 4, 6, and 8 mA). A total of 72 rats and 56 mice were included in the study. EA at LI11 increased the contractile amplitude of jejunal motility in the majority of both rats and mice. However, EA at LI11 did not enhance jejunal motility in rats administered atropine, rats that underwent vagotomy, and M 2 M 3 -‍‍/- mice (at all intensities). In WT mice, EA at LI11 significantly increased jejunal motility at all intensities except 1 mA, and a plateau was reached at intensities greater than 4 mA. Our results suggest that EA at LI11 promotes jejunal motility primarily by exciting the parasympathetic pathway, and that Aδ-fibres and C-fibres may play important roles in the process.

Disrupting vagal feedback affects birdsong motor control.

PubMed

Méndez, Jorge M; Dall'asén, Analía G; Goller, Franz

2010-12-15

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.

Disrupting vagal feedback affects birdsong motor control

PubMed Central

Méndez, Jorge M.; Dall'Asén, Analía G.; Goller, Franz

2010-01-01

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback. PMID:21113000

Reflex regulation of airway sympathetic nerves in guinea-pigs

PubMed Central

Oh, Eun Joo; Mazzone, Stuart B; Canning, Brendan J; Weinreich, Daniel

2006-01-01

Sympathetic nerves innervate the airways of most species but their reflex regulation has been essentially unstudied. Here we demonstrate sympathetic nerve-mediated reflex relaxation of airway smooth muscle measured in situ in the guinea-pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological analysis identified a population of substance P-containing capsaicin-sensitive spinal afferent neurones in the upper thoracic (T1–T4) dorsal root ganglia (DRG) that innervate the airways and lung. After bilateral vagotomy, atropine pretreatment and precontraction of the trachealis with histamine, nebulized capsaicin (10–60 μm) evoked a 63 ± 7% reversal of the histamine-induced contraction of the trachealis. Either the β-adrenoceptor antagonist propranolol (2 μm, administered directly to the trachea) or bilateral sympathetic nerve denervation of the trachea essentially abolished these reflexes (10 ± 9% and 6 ± 4% relaxations, respectively), suggesting that they were mediated primarily, if not exclusively, by sympathetic adrenergic nerve activation. Cutting the upper thoracic dorsal roots carrying the central processes of airway spinal afferents also markedly blocked the relaxations (9 ± 5% relaxation). Comparable inhibitory effects were observed following intravenous pretreatment with neurokinin receptor antagonists (3 ± 7% relaxations). These reflexes were not accompanied by consistent changes in heart rate or blood pressure. By contrast, stimulating the rostral cut ends of the cervical vagus nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were accompanied by marked alterations in blood pressure. The results indicate that the capsaicin-induced reflex-mediated relaxation of airway smooth muscle following vagotomy is mediated by sequential activation of tachykinin-containing spinal afferent and sympathetic efferent nerves innervating airways. This sympathetic nerve-mediated response may serve to oppose airway

Surgical perspectives in peptic ulcer disease and gastritis.

PubMed

Lipof, Tamar; Shapiro, David; Kozol, Robert-A

2006-05-28

For much of the twentieth century, surgery was frequently the solution for peptic ulcer disease. Our understanding of the pathophysiology of ulcers paralleled the development of potent pharmaceutical therapy. As the surgical world developed parietal cell vagotomy which would minimize the complications of surgery, patients failing medical therapy became rare. Emergent surgery for complicated peptic ulcers has not declined however. The development of proton pump inhibitors and the full understanding of the impact of H pylori has led to a trend towards minimalism in surgical therapy for complicated peptic ulcer disease. In addition to the changes in patient care, these developments have had an impact on the training of surgeons. This article outlines these trends and developments.

Gastroduodenal complications in kidney transplant recipients.

PubMed Central

Stuart, F P; Reckard, C R; Schulak, J A; Ketel, B L

1981-01-01

Oral antacids taken every two hours while awake provided the only prophylaxis against gastroduodenal ulceration for 167 kidney transplant recipients between 1968 and July 1978. Either perforation or major hemorrhage occurred in eight patients within 30 days after transplantation. Between July 1978 and January 1981, bleeding occurred within 30 days in two of 147 recipients who were treated with both antacids and cimetidine. Of the 147 patients, eleven with a history of ulcers had undergone pretransplant vagotomy; neither perforation nor hemorrhage occurred in any of the eleven patients. Despite reports that cimetidine enhances certain types of immune responses, we observed slightly greater graft survival in the group treated with cimetidine. PMID:7023396

Resection of terminal vagal branches to parietal cell mass in the treatment of duodenal ulcer.

PubMed Central

Sun, J M; Zhang, P; Shang, H

1984-01-01

In order to completely denervate the parietal cell mass and to prevent the undesirable side effects of highly selective vagotomy, the authors devised a new and simpler modified operative procedure. First, the anterior and posterior leaves of the lesser omentum are divided from the stomach at their attachment 6 cm proximal to the pylorus to the level 2 to 2.5 cm below the esophagogastric junction. Second, a circular seromuscular incision is made at the anterior and posterior wall of the stomach from the lesser curve 2 to 2.5 cm below the cardia to the highest short gastric artery at the greater curve. Forty cases followed for an average period of 21.8 months with satisfactory postoperative results reported. PMID:6486908

H1- and H2-receptor characterization in the tracheal circulation of sheep.

PubMed Central

Webber, S. E.; Salonen, R. O.; Widdicombe, J. G.

1988-01-01

1. The effects of histamine, the specific H1-agonist SKF 71481-A2 and the H2-agonist dimaprit were examined on tracheal vascular resistance in sheep anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. Changes in tracheal smooth muscle tone were also measured. 2. Histamine and SKF 71481-A2 contracted the tracheal smooth muscle and this effect was blocked by the H1-antagonist mepyramine. Stimulation of H2-receptors with dimaprit had no effect on tracheal smooth muscle tone. 3. Histamine had a complex action on the tracheal vasculature producing either a triphasic change (early dilatation then constriction followed by late dilatation) or just a constriction. SKF 71481-A2 always produced a biphasic change in vascular resistance (dilatation followed by constriction). Dimaprit dilated the tracheal vasculature. 4. The late dilatation produced by histamine in some sheep was blocked by bilateral cervical vagotomy but the mechanism for this effect is not known. No other responses to histamine, SKF 71481-A2 or dimaprit were affected by vagotomy. 5. The vasoconstriction produced by histamine and SKF 71481-A2 was antagonized by mepyramine indicating a H1-receptor-mediated effect. Cimetidine had no effect on the vasoconstriction to histamine suggesting a lack of involvement of H2-receptors. 6. The vasodilatation produced by histamine and SKF 71481-A2 was also antagonized by mepyramine, again suggesting a H1-receptor-mediated action. Cimetidine had no effect on the vasodilator response to histamine indicating no involvement of H2-receptors in this response. 7. The dilator effect of dimaprit was antagonized by cimetidine suggesting this effect was mediated by H2-receptors. 8. We conclude that H1-receptors in the various parts of the sheep tracheal vasculature can cause increases and decreases in total tracheal vascular resistance; that H2-receptors decrease

The herbal medicine, Dai-Kenchu-to, accelerates delayed gastrointestinal transit after the operation in rats.

PubMed

Fukuda, Hiroyuki; Chen, Cindy; Mantyh, Christopher; Ludwig, Kirk; Pappas, Theodore N; Takahashi, Toku

2006-04-01

Post-operative ileus (POI) is a transient bowel dysmotility after operation. We have previously shown that laparotomy alone significantly delayed gastrointestinal (GI) transit, compared to anesthesia alone. The GI transit was further delayed after laparotomy plus intestinal manipulation. Dai-Kenchu-to (DKT), an herbal medicine, has been used for treating adhesive bowel obstruction in Japan. We studied whether DKT improves delayed GI transit after the operation, with or without morphine administration in rats. Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the operation, the rats received 51Cr by gavage. Three hours after the operation, the rats were sacrificed and GI transit was estimated by calculating the geometric center (GC). DKT (120, 360, and 1,200 mg/kg) were administered by gavage after the operation, with or without morphine administration (1 mg/kg s.c.). A muscarinic receptor antagonist (atropine; 50 mug/kg), a 5HT3 receptor antagonist (ondansetron; 1 mg/kg) and a 5HT4 receptor antagonist (GR113,808; 3 mg/kg) were administered before the operation. Truncal vagotomy was performed preceding the operation. Laparotomy with intestinal manipulation produced a significant delay in GI transit (GC = 2.93 +/- 0.16), compared to that of anesthesia alone (9.51 +/- 0.45). DKT at the dose of 360 mg/kg (GC = 3.77 +/- 0.10, P < 0.01) and 1,200 mg/kg (GC = 3.77 +/- 0.20, P < 0.01) significantly accelerated delayed GI transit induced by operation. Ondansetron, GR113,808, atropine, and truncal vagotomy abolished the stimulatory effect of DKT (360 mg/kg). When morphine was administered, GI transit was further reduced (GC = 1.97 +/- 0.10). DKT at the dose of 360 mg/kg (GC = 2.81 +/- 0.22, P < 0.05) and 1,200 mg/kg (GC = 2.87 +/- 0.23, P < 0.05) significantly improved delayed GI transit in morphine treated rats. DKT accelerates delayed GI transit induced by intestinal manipulation with and without concomitant morphine

Orexigenic Hormone Ghrelin Attenuates Local and Remote Organ Injury after Intestinal Ischemia-Reperfusion

PubMed Central

Wu, Rongqian; Dong, Weifeng; Ji, Youxin; Zhou, Mian; Marini, Corrado P.; Ravikumar, Thanjavur S.; Wang, Ping

2008-01-01

Background Gut ischemia/reperfusion (I/R) injury is a serious condition in intensive care patients. Activation of immune cells adjacent to the huge endothelial cell surface area of the intestinal microvasculature produces initially local and then systemic inflammatory responses. Stimulation of the vagus nerve can rapidly attenuate systemic inflammatory responses through inhibiting the activation of macrophages and endothelial cells. Ghrelin, a novel orexigenic hormone, is produced predominately in the gastrointestinal system. Ghrelin receptors are expressed at a high density in the dorsal vagal complex of the brain stem. In this study, we investigated the regulation of the cholinergic anti-inflammatory pathway by the novel gastrointestinal hormone, ghrelin, after gut I/R. Methods and Findings Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 90 min in male adult rats. Our results showed that ghrelin levels were significantly reduced after gut I/R and that ghrelin administration inhibited pro-inflammatory cytokine release, reduced neutrophil infiltration, ameliorated intestinal barrier dysfunction, attenuated organ injury, and improved survival after gut I/R. Administration of a specific ghrelin receptor antagonist worsened gut I/R-induced organ injury and mortality. To determine whether ghrelin's beneficial effects after gut I/R require the intact vagus nerve, vagotomy was performed in sham and gut I/R animals immediately prior to the induction of gut ischemia. Our result showed that vagotomy completely eliminated ghrelin's beneficial effect after gut I/R. To further confirm that ghrelin's beneficial effects after gut I/R are mediated through the central nervous system, intracerebroventricular administration of ghrelin was performed at the beginning of reperfusion after 90-min gut ischemia. Our result showed that intracerebroventricular injection of ghrelin also protected the rats from gut I/R injury. Conclusions

Cholinergic aspects of cyanide intoxication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Von Bredow, J.D.; Vick, J.A.

1993-05-13

The acute exposure of pentobarbital anesthetized dogs to cyanide leads to a rapid increase and sudden halt in respiration accompanied by cardiovascular irregularities and extreme bradycardia which ultimately lead to cardiac arrest and death. Cardiac irregularities and cardiac arrest in the presence of cyanide induced respiratory arrest are assumed to be due to anoxia and therefore unresponsive to cardiotonic agents. Pretreatment or treatment with atropine sulfate or methyl atropine nitrate provides a marked reduction in the cardiovascular irregularities, bradycardia and hypotension. The cyanide induced cardiovascular effect can also be prevented by bilateral vagotomy. An intramuscularly injected combination of 20 mg/kgmore » sodium nitrite and 1 mg/kg of atropine sulfate ensured recovery of pentobarbital anesthetized dogs exposed to lethal concentrations (2.5 mg/kg i.v.) of sodium cyanide.« less

Use of the SeHCAT test in the investigation of diarrhoea.

PubMed Central

Ford, G. A.; Preece, J. D.; Davies, I. H.; Wilkinson, S. P.

1992-01-01

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea. PMID:1409191

Use of the SeHCAT test in the investigation of diarrhoea.

PubMed

Ford, G A; Preece, J D; Davies, I H; Wilkinson, S P

1992-04-01

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea.

Management of post-gastrectomy anastomosis site obstruction with a self-expandable metallic stent.

PubMed

Cha, Ra Ri; Lee, Sang Soo; Kim, Hyunjin; Kim, Hong Jun; Kim, Tae-Hyo; Jung, Woon Tae; Lee, Ok Jae; Bae, Kyung Soo; Jeong, Sang-Ho; Ha, Chang Yoon

2015-04-28

Post-gastrectomy anastomosis site obstruction is a relatively rare complication after a subtotal gastrectomy. We present a case of a 75-year-old man who underwent a truncal vagotomy, omental patch, gastrojejunostomy, and Braun anastomosis for duodenal ulcer perforation and a gastric outlet obstruction. Following the 10(th) postoperative day, the patient complained of abdominal discomfort and vomiting. We diagnosed post-gastrectomy anastomosis site obstruction by an upper gastrointestinal series and an upper endoscopic examination. We inserted a self-expandable metallic stent (SEMS) at the anastomosis site. The stent was fully expanded after deployment. On the day following the stent insertion, the patient began to eat, and his abdominal discomfort was resolved. This paper describes the successful management of post-gastrectomy anastomosis site obstruction with temporary placement of a SEMS.

Efferent limb of gastrojejunostomy obstruction by a whole okra phytobezoar: Case report and brief review

PubMed Central

Zin, Thant; Maw, Myat; Pai, Dinker Ramananda; Paijan, Rosaini Binti; Kyi, Myo

2012-01-01

A phytobezoar is one of the intraluminal causes of gastric outlet obstruction, especially in patients with previous gastric surgery and/or gastric motility disorders. Before the proton pump inhibitor era, vagotomy, pyloroplasty, gastrectomy and gastrojejunostomy were commonly performed procedures in peptic ulcer patients. One of the sequelae of gastrojejunostomy is phytobezoar formation. However, a bezoar causing gastric outlet obstruction is rare even with giant gastric bezoars. We report a rare case of gastric outlet obstruction due to a phytobezoar obstructing the efferent limb of the gastrojejunostomy site. This phytobezoar which consisted of a whole piece of okra (lady finger vegetable) was successfully removed by endoscopic snare. To the best of our knowledge, this is the first case of okra bezoar-related gastrojejunostomy efferent limb obstruction reported in the literature. PMID:22624073

The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Sutton, R. L.; Mckenna, Susan

1991-01-01

Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

Stimulatory effect of harmane and other beta-carbolines on locus coeruleus neurons in anaesthetized rats.

PubMed

Ruiz-Durántez, E; Ruiz-Ortega JA; Pineda, J; Ugedo, L

2001-08-10

Harmane, harmaline and norharmane are beta-carboline related compounds which have been proposed to be endogenous ligands for imidazoline receptors. The effect of these compounds on the activity of locus coeruleus (LC) neurons was studied by extracellular recordings techniques. Intracerebroventricular administration of harmane and harmaline increased the firing rate of LC neurons. Systemic administration of efaroxan, a mixed alpha(2)-adrenoceptor/I(1)-imidazoline antagonist or vagotomy failed to modify the harmane effect. Furthermore, local applications of harmane and harmaline increased the firing rate of LC neurons in a dose-related manner. Finally, intravenous administration of norharmane also increased the activity of LC neurons. Our results demonstrate that beta-carbolines stimulate LC neuron activity and indicate that this stimulation occurs directly in the LC by a mechanism independent of I(1)- and I(2)-imidazoline receptors.

Vection-induced gastric dysrhythmias and motion sickness

NASA Technical Reports Server (NTRS)

Koch, K. L.; Stern, R. M.

1986-01-01

Gastric electrical and mechanical activity during vection-induced motion sickness was investigated. The contractile events of the antrum and gastric myoelectric activity in healthy subjects exposed to vection were measured simultaneously. Symptomatic and myoelectric responses of subjects with vagotomy and gastric resections during vection stimuli were determined. And laboratory based computer systems for analysis of the myoelectric signal were developed. Gastric myoelectric activity was recorded from cutaneous electrodes, i.e., electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was induced by a rotating drum. gastric electromechanical activity was recorded during three periods: 15 min baseline, 15 min drum rotation (vection), and 15 to 30 min recovery. Preliminary results showed that catecholamine responses in nauseated versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias in two previously symptomatic subjects.

Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

NASA Astrophysics Data System (ADS)

Makale, Milan Theodore

This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

Cerebellar pressor response in the dog

NASA Technical Reports Server (NTRS)

Dormer, K. J.; Stone, H. L.

1976-01-01

A fastigial pressor response has been elicited in the anesthetized mongrel dog. Stimulation within the rostral portions of this nucleus results in mean arterial pressure rises up to 150 mmHg above control. A proportional tachycardia is simultaneously evoked which may rapidly attain heart rates of 190 beats/min above control levels. Peak tachycardias immediately subside and often the heart rate declines below control values during stimulation while arterial pressure remains elevated. When either the carotid sinuses were isolated by ligation or a bilateral vagotomy was performed, the fastigial tachycardia was sustained. The response could still be attained when submaximal doses of alpha-chloralose anesthesia or high levels of barbiturates (30-40 mg/kg) were given. Both portions of the response result from widespread sympathetic activation; however, buffering of the response through the baroreceptor reflexes is only demonstrated in the cardiac segment of the response.

Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs.

PubMed

Nakamura, H; Asano, T; Haruta, K; Takeda, K

1995-01-01

Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.

Role of nitric oxide in the control of the gastric motility within the nucleus ambiguus of rats.

PubMed

Sun, H-Z; Zhao, S-Z; Ai, H-B

2012-12-01

This study aims to investigate whether exogenous nitric oxide (NO) plays a role in controlling gastric motility within the nucleus ambiguus (NA). Experiments were performed on male Wistar rats anaesthetized with chloral hydrate. A latex balloon, connected to a pressure transducer, was inserted into the pylorus through the fundus for continuous recording of the change of gastric smooth muscle contractile curves. Microinjection of the NO-donor sodium nitroprusside (SNP; 5 nmol) or L-arginine (L-Arg; 5 nmol) into the NA significantly inhibited gastric motility, whereas the treatment of NO-synthase inhibitor N-nitro-L-arginine methylester (L-NAME) increased gastric motility remarkably. The negative effect of SNP or L-Arg on gastric motility was abolished by bilateral subdiaphragmatic vagotomy as well as by intravenous injection of ganglionic blocker, hexamethonium bromide (Hb). These results demonstrated that NO inhibited gastric motility by activating the cholinergic preganglionic neurons in the NA and through the mediation of vagus nerves.

Preabsorptive insulin release and hypoglycemia in rats.

PubMed

Louis-Sylvestre, J

1976-01-01

Peripheral blood glucose and immunologically reactive insulin levels were determined in freely moving normal rats which were submitted either to a free oral glucose load or to a gastric administration of the glucose load. Identical determinations were performed in ventromedial hypothalamic nucleus-(VMH) lesioned and vagotomized rats after the same oral intake. It was demonstrated that: 1) a free oral glucose intake was immediately followed by two peaks of insulun release and a resultant decrease in blood glucose; 2) a gastric glucose load resulted in a single peak of insulin release and the concomitant decline in blood glucose; 3) the recorded blood glucose level was the resultant of the insulin-induced hypoglycemia and the postabsorptive hyperglycemia; and 4) the responses were largely exaggerated in VMH-lesioned rats and abolished by vagotomy. It is concluded that the early prandial insulin release reflexly induced by food-related stimuli temporarily enhances the metabolic conditions which provoke feeding.

Electroacupuncture brain protection during ischemic stroke: A role for the parasympathetic nervous system.

PubMed

Chi, Laiting; Du, Kairong; Liu, Dongdong; Bo, Yulong; Li, Wenzhi

2018-03-01

The demand for using parasympathetic activation for stroke therapy is unmet. In the current study, we investigated whether the neuroprotection provided by electroacupuncture (EA) in an experimental stroke model was associated with activation of the parasympathetic nervous system (PNS). The results showed that parasympathetic dysfunction (PD), performed as unilateral vagotomy combined with peripheral atropine, attenuated both the functional benefits of EA and its effects in improving cerebral perfusion, reducing infarct volume, and hindering apoptosis, neuronal and peripheral inflammation, and oxidative stress. Most importantly, EA rats showed a dramatically less reduction in the mRNA level of choline acetyltransferase, five subtypes of muscarinic receptors and α7nAChR, suggesting the inhibition of the impairment of the central cholinergic system; EA also activated dorsal motor nucleus of the vagus, the largest source of parasympathetic pre-ganglionic neurons in the lower brainstem (detected by c-fos immunohistochemistry), and PD suppressed these changes. These findings indicated EA may serve as an alternative modality of PNS activation for stroke therapy.

Cardiorespiratory activity of C-terminal pentapeptide of substance P in anaesthetized rats.

PubMed

Wojciechowski, Piotr; Szereda-Przestaszewska, Małgorzata; Lipkowski, Andrzej Wojciech

2016-11-01

Experiments were performed in anaesthetized, spontaneously breathing rats to: (1) analyse the respiratory and cardiovascular effects of C-terminal fragment of substance P (AWL2077) as referred to those exerted by the parent undecapeptide, (2) determine the involvement of lung vagal afferents to these responses. Each peptide was injected intravenously at a dose of 0.3μmol/kg into neurally intact or midcervically vagotomized rats. Administration of both compounds decreased tidal volume, minute ventilation, mean arterial blood pressure and heart rate, showing stimulatory (SP) and depressive (AWL2077) effects on the rate of breathing. Midcervical vagotomy reversed (post-SP) and precluded (post-AWL2077) respiratory rate responses and eliminated bradycardia evoked by both peptides. These findings indicate that the examined C-terminal pentapeptide was convergent with, but less potent than substance P in central depression of tidal volume and displayed divergence in the peripheral effect on respiratory timing. Copyright © 2016 Elsevier B.V. All rights reserved.

Lack of evidence in vivo for a remote effect of Escherichia coli heat stable enterotoxin on jejunal fluid absorption.

PubMed

Lucas, M L; Duncan, N W; o'reilly, N F; McIlvenny, T J; Nelson, Y B

2008-05-01

On contact with the mucosa, heat stable (STa) enterotoxin from Escherichia coli reduces fluid absorption in vivo in the perfused jejunum of the anaesthetized rat. The question of whether it also has a vagally mediated remote action on jejunal absorption, when instilled into the ileum, was re-examined, given contradictory findings in the literature. A standard perfused loop preparation was used to measure luminal uptake of fluid in vivo by means of volume recovery. STa in the ileum was found to have no effect on jejunal absorption, regardless of cervical or sub-diaphragmatic vagotomy and also regardless of the nature of the perfusate anion. The batches of toxin were shown in parallel experiments to reduce fluid absorption directly in the jejunum and also in the ileum. Similarly, vagal nerves prior to section had demonstrable in vivo physiological function. There was therefore no evidence for an indirect, vagally mediated ileal effect of STa on proximal fluid absorption.

Studies on gastric bicarbonate secretion in man.

PubMed

Forssell, H

1987-01-01

A method for measurement of human basal and stimulated gastric bicarbonate secretion was developed in the present investigation. The mechanisms involved in the regulation of basal, vagus nerve stimulated as well as fundic distension induced bicarbonate secretion were studied. The investigations were performed in healthy subjects and duodenal ulcer patients, the latter group before and/or after a proximal gastric vagotomy operation. Healthy subjects as well as ulcer patients were premedicated with a histamine H2-receptor antagonist and gastric bicarbonate secretion was determined by use of a gastric perfusion system in combination with computerized continuous recordings of pH and PCO2. The contribution of alkaline saliva to the measured gastric bicarbonate secretion was minimized by continuous salivary suction and correction was made for swallowed saliva by measurement of amylase in the gastric aspirate. A high rate of gastric perfusion facilitated the identification of alkaline duodenogastric reflux and also eliminated its influence on the measurement of gastric bicarbonate secretion. Validation of the measuring system by instillation of small amounts of bicarbonate showed a satisfactory correlation between added and recovered bicarbonate in the range of bicarbonate determinations usually recorded. Decreasing intragastric pH to between 3 and 4 converted all secreted bicarbonate into CO2, but did not affect the measured value of bicarbonate secretion. Vagal stimulation accomplished by sham feeding increased gastric bicarbonate secretion in sixteen healthy subjects from 410 +/- 39 mumol/h to 692 +/- 67 mumol/h (mean +/- SEM, p less than 0.001). This response was independent of intragastric pH in the range of 2 to 7. The muscarinic receptor antagonist, benzilonium bromide, almost abolished the sham feeding response while indomethacin left it nearly unchanged. Nine duodenal ulcer patients had identical basal and vagally stimulated bicarbonate output as healthy subjects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amaral, H.; Palma, R.; Pfau, J.

Bile acid malabsorption has been recognized as an important cause of chronic diarrhea. Se-75HCAT, a bile acid, is absorbed in the terminal ileum. Therefore, measurement of its body retention indicate ileal function not requiring fecal collections. The authors studied 8 normal volunteers presenting with chronic recurrent diarrhea for more than 2 years. Each received orally a 10 ..mu..Ci capsule of SeHCAT (Amersham Intl.) and 3 hours later anterior and posterior whole body activity was measured using a digital camera without collimator. Measurements were repeated daily for 7 days and expressed as % of retention. Three patients had normal retention (1more » celiac disease, 1 inactive Crohn disease and 1 functional diarrhea), another was borderline (an immunodeficiency) and 4 patients presented abnormal bile acid absorption (2 had vagotomy, 1 Crohn disease and 1 idiopathic diarrhea). This last group was treated with cholestyramine showing improvement of the diarrhea, and relapse on drug withdrawal. These findings demonstrate that this technique can identify bile acid malabsorption as the cause of chronic diarrhea by external counting.« less

[Mannheim peritonitis index as a surgical criterion for perforative duodenal ulcer].

PubMed

Krylov, N N; Babkin, O V; Babkin, D O

to define the correlation between Mannheim peritonitis index scores and outcomes of different radical and palliative interventions for perforative duodenal ulcer. Treatment of 386 patients with perforative duodenal ulcer is presented. Different surgical techniques were analyzed including stomach resection, various methods of vagotomy with/without drainage, ulcer suturing and ulcerative edges excision with suturing in patients with Mannheim index scores <21, 21-29 and over 29. Clavien-Dindo classification was used to analyze postoperative complications. In 64.3% of cases mortality was caused by peritonitis and peritonitis-associated complications. Surgical features resulted unfavorable outcome only in 35.7% of cases. Severe complications requiring re-operation were predominantly observed after stomach resection. Mannheim peritonitis index is sensitive method allowing prognosis the outcomes in patients with perforative duodenal ulcer. Radical interventions are advisable in Mannheim index scores <21, in other cases palliative surgery for example suturing or edges excision with suturing is preferred. If radical surgery is performed with strict indications (Mannheim index scores <21) volume and type of surgery do not significantly influence on mortality rate.

Central effects of humanin on hepatic triglyceride secretion.

PubMed

Gong, Zhenwei; Su, Kai; Cui, Lingguang; Tas, Emir; Zhang, Ting; Dong, H Henry; Yakar, Shoshana; Muzumdar, Radhika H

2015-08-01

Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism. Copyright © 2015 the American Physiological Society.

Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.

PubMed Central

Houghton, P. W.; Leach, S.; Owen, R. W.; McC Mortensen, N. J.; Hill, M. J.; Williamson, R. C.

1989-01-01

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds. PMID:2765371

Duodenal GLP-1 signaling regulates hepatic glucose production through a PKC-δ-dependent neurocircuitry

PubMed Central

Yang, Mengliu; Wang, Jinzhi; Wu, Shaobo; Yuan, Lei; Zhao, Xiaodong; Liu, Chaohong; Xie, Jing; Jia, Yanjun; Lai, Yerui; Zhao, Allan Zijian; Boden, Guenther; Li, Ling; Yang, Gangyi

2017-01-01

Intestinal glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion and acts as a neuropeptide to control glucose homeostasis, but little is known whether intestinal GLP-1 has any effect in the control of hepatic glucose production (HGP). Here we found that intraduodenal infusion of GLP-1 activated duodenal PKC-δ, lowered HGP and was accompanied by a decrease in hepatic expression of gluconeogenic enzymes and an increase in hepatic insulin signaling in rats. However, gut co-infusion of either the GLP-1 receptor antagonist Ex-9, or the PKC-δ inhibitor rottlerin with GLP-1, negated the ability of gut GLP-1 to lower HGP and to increase hepatic insulin signaling during clamps. The metabolic and molecular signal effects of duodenal GLP-1 were also negated by co-infusion with tetracaine, pharmacologic inhibition of N-methyl-d-aspartate receptors within the dorsalvagal complex, or hepatic vagotomy in rats. In summary, we identified a neural glucoregulatory function of gut GLP-1 signaling. PMID:28182013

Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.

PubMed

Furuta, Sadayoshi; Watanabe, Lisa; Doi, Seira; Horiuchi, Hiroshi; Matsumoto, Kenjiro; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2012-02-01

Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Copyright © 2011 Wiley Periodicals, Inc.

[Results of the 75selenium homotaurocholic acid retention test (SeHCAT test) in diagnosis of diarrhea].

PubMed

Balzer, K; Schmitt, G; Reiners, C; Goebell, H

1995-01-15

For that reason absorption of bile acids was investigated using the 75Se-homotaurocholate (SeHCAT) in 239 patients with diarrhoea. SeHCAT retention time was measured as 7 day retention time in a whole body counter. An intact bile acid absorption (negative SeHCAT test) was confirmed in 23 healthy volunteers within the range of 11 to 50% (mean +/- double standard deviation). In 135 patients with a possible type I bile salt malabsorption the SeHCAT test was positive in 78%, thus indicating bile salt malabsorption. The test is very sensitive detecting bile salt malabsorption in Crohn's disease, identifying ileal disease more precisely than radiology. The SeHCAT test ascertained type II primary bile salt malabsorption in 7 patients, as well as type III bile salt malabsorption in patients (9 out of 28) with cholecystectomy, vagotomy, partial gastrectomy and chronic pancreatitis. In addition, a positive SeHCAT test indicating bile acid malabsorption was found in 5 out of 11 patients with irritable syndrome, diarrhoeic form, and in 4 out of 12 patients with lactose intolerance. SeHCAT retention should be measured routinely in patients with chronic diarrhoea for which the cause is not obvious.

Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.

PubMed

Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

2015-10-26

Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.

Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury

PubMed Central

Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

2015-01-01

Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion. PMID:26499847

Endogenous acetylcholine increases alveolar epithelial fluid transport via activation of alveolar epithelial Na,K-ATPase in mice.

PubMed

Li, Xia; Yan, Xi Xin; Li, Hong Lin; Li, Rong Qin

2015-10-01

The contribution of endogenous acetylcholine to alveolar fluid clearance (AFC) and related molecular mechanisms were explored. AFC was measured in Balb/c mice after vagotomy and vagus nerve stimulation. Effects of acetylcholine chloride on AFC in Kunming mice and Na,K-ATPase function in A549 alveolar epithelial cells also were determined. AFC significantly decreased in mice with left cervical vagus nerve transection compared with controls (48.69 ± 2.57 vs. 66.88 ± 2.64, P ≤ 0.01), which was reversed by stimulation of the peripheral (60.81 ± 1.96, P ≤ 0.01). Compared with control, acetylcholine chloride dose-dependently increased AFC and elevated Na,K-ATPase activity, and these increases were blocked or reversed by atropine. These effects were accompanied by recruitment of Na,K-ATPase α1 to the cell membrane. Thus, vagus nerves participate in alveolar epithelial fluid transport by releasing endogenous acetylcholine in the infusion-induced pulmonary edema mouse model. Effects of endogenous acetylcholine on AFC are likely mediated by Na,K-ATPase function through activation of muscarinic acetylcholine receptors on alveolar epithelia. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute increases in arterial blood pressure produced by occlusion of the abdominal aorta induces antinociception: peripheral and central substrates.

PubMed

Thurston, C L; Randich, A

1990-06-11

Occlusion of the abdominal aorta proximal to the renal arteries results in an increase in arterial blood pressure, inhibition of forepaw and hindpaw withdrawal to a noxious mechanical stimulus, and inhibition of the tail-flick reflex to noxious heat. Occlusion of the abdominal aorta distal to the renal arteries does not elevate arterial blood pressure and produces no antinociceptive effects. Occlusion of the vena cava lowers arterial blood pressure and produces no antinociception. The inhibitory effects of occlusion of the abdominal aorta depend upon activation of high pressure baroreceptors since bilateral sinoaortic denervation, but not bilateral vagotomy, eliminates the inhibition with respect to all behavioral measures. The inhibitory effects with respect to the tail-flick reflex also depend upon activation of a descending inhibitory system since reversible cold block of the spinal cord at the level of the second thoracic vertebra eliminates the antinociception. This antinociception is also eliminated following intrathecal administration of the noradrenergic receptor antagonist phentolamine, but not by intrathecal administration of either methysergide or naloxone. These data support the view that activation of high pressure baroreceptors by increases in arterial blood pressure produces antinociception via activation of a spinopetal noradrenergic system.

[The effects of caffeine on the respiratory depression by morphine].

PubMed

Kasaba, T; Takeshita, M; Takasaki, M

1997-12-01

The effects of intravenous administration of caffeine on the discharge of the phrenic nerve were studied following vagotomy in 7 pentobarbital anesthetized mechanically ventilated rats. Morphine (0.4 mg.kg-1.min-1) was administered until the respiratory rate decreased to about half of the baseline respiratory rate. In those state, we first administered caffeine (20 mg.kg-1), intravenously and then administered naloxone (0.02 mg) intravenously. The increase of inspiratory time from 0.49 +/- 0.16 to 2.01 +/- 0.47 s by morphine recovered to 0.86 +/- 0.38 s by caffeine and 0.50 +/- 0.22 s by naloxone. Expiratory time did not change during each drug administration. The decrease of respiratory rate from 46.6 +/- 5.9 to 20.6 +/- 4.1 breaths.min-1 by morphine recovered to 39.6 +/- 6.1 breaths.min-1 by caffeine and 47.6 +/- 4.6 breaths.min-1 by naloxone. Amplitude of integrated phrenic nerve discharge increased to 117 +/- 32% by caffeine and 156 +/- 39% by naloxone compared to the baseline. These results suggest that caffeine acts as a respiratory stimulant on the respiratory depression by morphine.

Gastric mucosal damage in water immersion stress: mechanism and prevention with GHRP-6.

PubMed

Guo, Shu; Gao, Qian; Jiao, Qing; Hao, Wei; Gao, Xue; Cao, Ji-Min

2012-06-28

To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress (WRS) and its prevention by growth hormone releasing peptide-6 (GHRP-6). Male Wistar rats were subjected to conscious or unconscious (anesthetized) WRS, simple restraint (SR), free swimming (FS), non-water fluid immersion, immersion without water contact, or rats were placed in a cage surrounded by sand. To explore the sensitivity structures that influence the stress reaction besides skin stimuli, a group the rats had their eyes occluded. Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage. Gastric mucosal lesions, acid output and heart rate variability were measured. Plasma renin, endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed. GHRP-6 was injected [intraperitoneal (IP) or intracerebroventricular (ICV)] 2 h before the onset of stress to observe its potential prevention of the mucosal lesion. WRS for 6 h induced serious gastric mucosal lesion [lesion area, WRS 81.8 ± 6.4 mm² vs normal control 0.0 ± 0.0 mm², P < 0.01], decreased the heart rate, and increased the heart rate variability and gastric acid secretion, suggesting an increase in vagal nerve-carrying stimuli. The mucosal injury was inversely correlated with water temperature (lesion area, WRS at 35 °C 56.4 ± 5.2 mm² vs WRS at 23 °C 81.8 ± 6.4 mm², P < 0.01) and was consciousness-dependent. The injury could not be prevented by eye occlusion, but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit. When water was replaced by vegetable oil or liquid paraffin, there were gastric lesions in the same grade of water immersion. When rat were placed in a cage surrounded by sand, there were no gastric lesions. All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by

Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats.

PubMed

Kawada, Toru; Akiyama, Tsuyoshi; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

2017-07-01

Desipramine (DMI) is a blocker of neuronal norepinephrine (NE) uptake transporter. Although intravenous DMI has been shown to cause centrally-mediated sympathoinhibition and peripheral NE accumulation, its parasympathetic effect remains to be elucidated. We hypothesized that intravenous DMI activates the cardiac vagal nerve via an α 2 -adrenergic mechanism. Using a cardiac microdialysis technique, changes in myocardial interstitial acetylcholine (ACh) levels in the left ventricular free wall in response to intravenous DMI (1mg·kg -1 ) were examined in anesthetized rats. In rats with intact vagi (n=7), intravenous DMI increased ACh from 1.67±0.43 to 2.48±0.66nM (P<0.01). In rats with vagotomy (n=5), DMI did not significantly change ACh (from 0.92±0.16 to 0.85±0.23nM). In rats with intact vagi pretreated with intravenous yohimbine (2mg·kg -1 ), DMI did not significantly change ACh (from 1.25±0.23 to 1.13±0.15nM). In conclusion, while DMI is generally considered to be an agent that predominantly affects sympathetic neurotransmission, it can activate the cardiac vagal nerve via α 2 -adrenergic stimulation in experimental settings in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy.

PubMed

Nguyen, Sheila; Hojjati, Mehrnaz

2011-01-01

Hypertrophic osteoarthropathy (HOA) is a disabling condition that may occur secondarily to primary lung cancer. It is characterized by digital clubbing, arthralgia/arthritis, and periostosis of the tubular bones. The pain associated with HOA can be disabling and often refractory to conventional analgesics. We performed a comprehensive review of the literature using the PubMed database on treatment modalities available for HOA. We found 52 relevant articles-40 case reports, six case series, two review papers, and four combined case series and review papers. There were no randomized controlled trials reported. We then classified treatments used for HOA into two categories: (1) treatment of primary cause (i.e., resection of tumor, chemotherapy, radiotherapy, treatment of infection, etc.) and (2) symptomatic treatments (i.e., bisphosphonates, octreotide, NSAIDs, vagotomy, etc.). Subsequently, we summarized the main findings for each treatment. Although the clinical diagnosis of HOA has existed for over 100 years, the pathogenesis mechanism has not yet been elucidated, and treatment options for this condition remain experimental. Primary treatment is the most widely reported modality to be efficacious. In cases which primary therapy is not possible, several symptomatic treatment modalities are suggested, with various degree of success. Further research is needed to clarify the pathophysiological mechanism of HOA as to appropriately direct therapy.

The effect of (+)-lysergic acid diethylamide and other drugs on the carotid sinus reflex

PubMed Central

Ginzel, K. H.

1958-01-01

In cats, lysergic acid diethylamide (LSD) selectively blocked the reflex blood pressure rise following carotid chemoreceptor stimulation. It also reduced or abolished the chemoreceptor component of the pressor response to occlusion of the common carotid arteries. It did not inhibit the respiratory reflexes arising from the carotid chemoreceptors, unless spontaneous respiration was interfered with as a whole. The site of action was central, probably below the intercollicular level, regardless of whether the drug was administered by the intravenous route or into the lateral ventricle of the brain. LSD did not block the baroreceptor depressor reflex elicited by stimulation of one carotid sinus nerve. LSD frequently caused the systemic pressure to fall, even after vagotomy and atropine, and this effect might account for the occasional reduction of the baroreceptor component of the carotid occlusion response. On the other hand, no relationship was found between the action of LSD on vasomotor tone and its blocking effect on the chemoreceptor pressor reflex. Some derivatives of LSD produced effects similar to those described for LSD, whether or not they possessed a psychotropic action in man, and independently of their efficiency as antagonists to 5-hydroxytryptamine. Of a series of compounds chemically unrelated to LSD, chlorpromazine was found to block the chemoreceptor pressor rise after intracerebroventricular injection. PMID:13584725

Intraportal infusion of ghrelin could inhibit glucose-stimulated GLP-1 secretion by enteric neural net in Wistar rat.

PubMed

Zhang, Xiyao; Li, Wensong; Li, Ping; Chang, Manli; Huang, Xu; Li, Qiang; Cui, Can

2014-01-01

As a regulator of food intake and energy metabolism, the role of ghrelin in glucose metabolism is still not fully understood. In this study, we determined the in vivo effect of ghrelin on incretin effect. We demonstrated that ghrelin inhibited the glucose-stimulated release of glucagon-like peptide-1 (GLP-1) when infused into the portal vein of Wistar rat. Hepatic vagotomy diminished the inhibitory effect of ghrelin on glucose-stimulated GLP-1 secretion. In addition, phentolamine, a nonselective α receptor antagonist, could recover the decrease of GLP-1 release induced by ghrelin infusion. Pralmorelin (an artificial growth hormone release peptide) infusion into the portal vein could also inhibit the glucose-stimulated release of GLP-1. And growth hormone secretagogue receptor antagonist, [D-lys3]-GHRP-6, infusion showed comparable increases of glucose stimulated GLP-1 release compared to ghrelin infusion into the portal vein. The data showed that intraportal infusion of ghrelin exerted an inhibitory effect on GLP-1 secretion through growth hormone secretagogue receptor 1α (GHS1α receptor), which indicated that the downregulation of ghrelin secretion after food intake was necessary for incretin effect. Furthermore, our results suggested that the enteric neural net involved hepatic vagal nerve and sympathetic nerve mediated inhibition effect of ghrelin on incretin effect.

The effect of (+)-lysergic acid diethylamide and other drugs on the carotid sinus reflex.

PubMed

GINZEL, K H

1958-09-01

In cats, lysergic acid diethylamide (LSD) selectively blocked the reflex blood pressure rise following carotid chemoreceptor stimulation. It also reduced or abolished the chemoreceptor component of the pressor response to occlusion of the common carotid arteries. It did not inhibit the respiratory reflexes arising from the carotid chemoreceptors, unless spontaneous respiration was interfered with as a whole. The site of action was central, probably below the intercollicular level, regardless of whether the drug was administered by the intravenous route or into the lateral ventricle of the brain.LSD did not block the baroreceptor depressor reflex elicited by stimulation of one carotid sinus nerve. LSD frequently caused the systemic pressure to fall, even after vagotomy and atropine, and this effect might account for the occasional reduction of the baroreceptor component of the carotid occlusion response. On the other hand, no relationship was found between the action of LSD on vasomotor tone and its blocking effect on the chemoreceptor pressor reflex.Some derivatives of LSD produced effects similar to those described for LSD, whether or not they possessed a psychotropic action in man, and independently of their efficiency as antagonists to 5-hydroxytryptamine. Of a series of compounds chemically unrelated to LSD, chlorpromazine was found to block the chemoreceptor pressor rise after intracerebroventricular injection.

[Modulation of the cholinergic system during inflammation].

PubMed

Nezhinskaia, G I; Vladykin, A L; Sapronov, N S

2008-01-01

This review describes the effects of realization of the central and peripheral "cholinergic antiinflammatory pathway" in a model of endotoxic and anaphylactic shock. Under endotoxic shock conditions, a pharmacological correction by means of the central m-cholinomimetic action (electrical stimulation of the distal ends of nervus vagus after bilateral cervical vagotomy, surgical implantation of the stimulant devise, activation of efferent vagal neurons by means of muscarinic agonist) is directed toward the elimination of LPS-induced hypotension. During the anaphylaxis, peripheral effects of the cholinergic system induced by blocking m-AChR on the target cells (neuronal and non-neuronal lung cells) and acetylcholinesterase inhibition are related to suppression of the bronchoconstrictor response. The role of immune system in the pathogenesis of endotoxic shock is associated with the production of proinflammatory cytokines by macrophages, increase in IgM concentration, and complement activation, while the role in the pathogenesis of anaphylactic shock is associated with IgE, IgG1 augmentation. Effects of B cell stimulation may be important in hypoxia and in the prophylaxis of stress ulcers and other diseases. Plasma proteins can influence the effects of the muscarinic antagonist methacine: IgG enhance its action while albumin and CRP abolish it.

One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

PubMed

Waise, T M Zaved; Toshinai, Koji; Naznin, Farhana; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu

2015-09-04

A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Glucagon-like peptide-1 reduces pancreatic β-cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats.

PubMed

Ando, Hisae; Gotoh, Koro; Fujiwara, Kansuke; Anai, Manabu; Chiba, Seiichi; Masaki, Takayuki; Kakuma, Tetsuya; Shibata, Hirotaka

2017-07-17

We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese rats elevated c-fos expression and BDNF content in the hypothalamus, followed by a reduction in pancreatic β-cell hyperplasia and insulin content, thus resulting in improved glucose tolerance. These responses were abolished by VgX and SpX. Moreover, administration of liraglutide similarly activated the hypothalamic neural pathways, thus resulting in a more profound amelioration of glucose tolerance than native GLP-1 (7-36). These data suggest that GLP-1 normalizes the obesity-induced compensatory increase in β-cell mass and glucose intolerance through a neuronal relay system consisting of hepatic afferent nerves, the hypothalamus, and pancreatic efferent nerves.

Surgery for Peptic Ulcer Disease in sub-Saharan Africa: Systematic Review of Published Data.

PubMed

Rickard, Jennifer

2016-04-01

Peptic ulcer disease is a significant cause of morbidity and mortality worldwide, with a significant burden in low- and middle-income countries. However, there is limited information regarding management of peptic ulcer disease in these countries. This study describes surgical interventions for peptic ulcer disease in sub-Saharan Africa. A systematic review was performed using PubMed, EMBASE, and African Index Medicus for studies describing surgical management of peptic ulcer disease in sub-Saharan Africa. From 55 published reports, 6594 patients underwent surgery for peptic ulcer disease. Most ulcers (86%) were duodenal with the remainder gastric (14%). Thirty-five percent of operations were performed for perforation, 7% for bleeding, 30% for obstruction, and 28% for chronic disease. Common operations included vagotomy (60%) and primary repair (31%). The overall case fatality rate for peptic ulcer disease was 5.7% and varied with indication for operation: 13.6% for perforation, 11.5% for bleeding, 0.5% for obstruction, and 0.3% for chronic disease. Peptic ulcer disease remains a significant indication for surgery in sub-Saharan Africa. Recognizing the continued role of surgery for peptic ulcer disease in sub-Saharan Africa is important for strengthening surgical training programs and optimizing allocation of resources.

An overview of history, pathogenesis and treatment of perforated peptic ulcer disease with evaluation of prognostic scoring in adults.

PubMed

Prabhu, V; Shivani, A

2014-01-01

Peptic ulcer disease including both gastric and duodenal ulcer form a substantial part of patients seeking surgical opinion world-wide. The concept of acid in peptic ulcer disease, which was the basis of treatment of peptic ulcer was revolutionized by the discovery of H2-receptor antagonists, that led to the principle of acid suppression therapy for duodenal ulcer which followed decades of preference for surgical interventions in the form of gastric resections, vagotomy etc., After the discovery of Helicobacter pylori organism as the causative factor a triple drug regime was identified to treat peptic disease which was further modified to sequential therapy to avoid antibiotic resistance. This recognition has not concluded the chapter on peptic ulcers. The management of ulcer disease and its complications remain a surgical challenge. All the materials for this review have been accessed from various internet search engines. The references have been narrowed down to 34 by excluding cross references, duplicated citations, pediatric studies, case reports, iatrogenic and malignant perforations and including microbiological, immunohistochemistry references and studies with more than a sample size of ten. Case control, cohort studies, prospective/retrospective, metaanalytical studies were preferred in that order. This article attempts to take an overview of all aspects of the management of peptic ulcer.

Model of a training program in robotic surgery and its initial results.

PubMed

Madureira, Fernando Athayde Veloso; Varela, José Luís Souza; Madureira, Delta; D'Almeida, Luis Alfredo Vieira; Madureira, Fábio Athayde Veloso; Duarte, Alexandre Miranda; Vaz, Otávio Pires; Ramos, José Reinan

2017-01-01

to describe the implementation of a training program in robotic surgery and to point the General Surgery procedures that can be performed with advantages using the robotic platform. we conducted a retrospective analysis of data collected prospectively from the robotic surgery group in General and Colo-Retal Surgery at the Samaritan Hospital (Rio de Janeiro, Brazil), from October 2012 to December 2015. We describe the training stages and particularities. two hundred and ninety three robotic operations were performed in general surgery: 108 procedures for morbid obesity, 59 colorectal surgeries, 55 procedures in the esophago-gastric transition area, 16 cholecystectomies, 27 abdominal wall hernioplasties, 13 inguinal hernioplasties, two gastrectomies with D2 lymphadenectomy, one vagotomy, two diaphragmatic hernioplasties, four liver surgeries, two adrenalectomies, two splenectomies, one pancreatectomy and one bilio-digestive anastomosis. The complication rate was 2.4%, with no major complications. the robotic surgery program of the Samaritan Hospital was safely implemented and with initial results better than the ones described in the current literature. There seems to be benefits in using the robotic platform in super-obese patients, re-operations of obesity surgery and hiatus hernias, giant and paraesophageal hiatus hernias, ventral hernias with multiple defects and rectal resections.

Perforated peptic ulcer following gastric bypass for obesity.

PubMed

Macgregor, A M; Pickens, N E; Thoburn, E K

1999-03-01

Peptic ulcer in the excluded segment of a gastric bypass performed in the management of morbid obesity has only rarely been reported in the literature. The purpose of this study is to review our experience with the condition in a series of 4300 patients who underwent gastric-restrictive surgery between 1978 and 1997. Eleven patients presented with acute perforation of a peptic ulcer in the excluded gastric segment. Nine ulcers were duodenal, one was gastric, and one patient had both gastric and duodenal perforations. The time between primary gastric-restrictive surgery and ulcer perforation varied from 20 days to 12 years. All patients presented with upper abdominal pain. The classical radiological sign of perforated peptic ulcer, free air under the diaphragm, did not occur in any patient. Nine patients were initially treated by primary closure of the perforation with subsequent definitive ulcer therapy by vagotomy, pyloroplasty, or gastrectomy. One case, initially treated elsewhere, was managed by placement of a Malecot catheter through the duodenal perforation, gastrostomy, and peritoneal drainage. One recent case remains symptom-free on H2 blockers after simple closure. There was no mortality. Six cases were previously reported in the literature with a 33 per cent mortality rate.

The role of arterial chemoreceptors in the breath-by-breath augmentation of inspiratory effort in rabbits during airway occlusion or elastic loading.

PubMed

Callanan, D; Read, D J

1974-08-01

1. The breath-by-breath augmentation of inspiratory effort in the five breaths following airway occlusion or elastic loading was assessed in anaesthetized rabbits from changes of airway pressure, diaphragm e.m.g. and lung volume.2. When the airway was occluded in animals breathing air, arterial O(2) tension fell by 20 mmHg and CO(2) tension rose by 7 mmHg within the time of the first five loaded breaths.3. Inhalation of 100% O(2) or carotid denervation markedly reduced the breath-by-breath progression but had little or no effect on the responses at the first loaded breath.4. These results indicate that the breath-by-breath augmentation of inspiratory effort following addition of a load is mainly due to asphyxial stimulation of the carotid bodies, rather than to the gradual emergence of a powerful load-compensating reflex originating in the chest-wall, as postulated by some workers.5. The small residual progression seen in animals breathing 100% O(2) or following carotid denervation was not eliminated (a) by combining these procedures or (b) by addition of gas to the lungs to prevent the progressive lung deflation which occurred during airway occlusion.6. Bilateral vagotomy, when combined with carotid denervation, abolished the residual breath-by-breath progression of inspiratory effort.

An Overview of History, Pathogenesis and Treatment of Perforated Peptic Ulcer Disease with Evaluation of Prognostic Scoring in Adults

PubMed Central

Prabhu, V; Shivani, A

2014-01-01

Peptic ulcer disease including both gastric and duodenal ulcer form a substantial part of patients seeking surgical opinion world-wide. The concept of acid in peptic ulcer disease, which was the basis of treatment of peptic ulcer was revolutionized by the discovery of H2-receptor antagonists, that led to the principle of acid suppression therapy for duodenal ulcer which followed decades of preference for surgical interventions in the form of gastric resections, vagotomy etc., After the discovery of Helicobacter pylori organism as the causative factor a triple drug regime was identified to treat peptic disease which was further modified to sequential therapy to avoid antibiotic resistance. This recognition has not concluded the chapter on peptic ulcers. The management of ulcer disease and its complications remain a surgical challenge. All the materials for this review have been accessed from various internet search engines. The references have been narrowed down to 34 by excluding cross references, duplicated citations, pediatric studies, case reports, iatrogenic and malignant perforations and including microbiological, immunohistochemistry references and studies with more than a sample size of ten. Case control, cohort studies, prospective/retrospective, metaanalytical studies were preferred in that order. This article attempts to take an overview of all aspects of the management of peptic ulcer. PMID:24669326

The role of substance P release in the lung with esophageal acid.

PubMed

Kohrogi, H; Hamamoto, J; Kawano, O; Iwagoe, H; Fujii, K; Hirata, N; Ando, M

2001-12-03

To investigate whether tachykinins are released in the airways by stimulating the esophagus, airway plasma extravasation induced by intraesophageal hydrochloric acid (HCl) in the presence or absence of the neutral endopeptidase (NEP) inhibitor phosphoramidon and the neurokinin-1-receptor antagonist FK888 was studied in anesthetized guinea pigs. Airway plasma extravasation also was studied in the presence of the NEP inhibitor in guinea pigs pretreated with capsaicin or bilateral vagotomy. Propranolol and atropine were used in all animals to block adrenergic and cholinergic nerve effects. Airway plasma leakage was evaluated by measuring extravasated Evans blue dye. One normal HCl infusion into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation induced by HCl infusion into the esophagus in the trachea and main bronchi, and FK888 significantly inhibited extravasation in a dose-related manner. In capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilaterally vagotomized animals. These results suggest that locally acting substances are released by intraesophageal HCl stimulation that cause airway plasma extravasation. These substances are generated through activation of neural pathways, including some that traffic through the vagus nerves that link the esophagus or airways.

Low back pain caused by a duodenal ulcer.

PubMed

Weiss, D J; Conliffe, T; Tata, N

1998-09-01

The common diagnoses in low back pain are lumbar strain, lumbosacral radiculopathy, osteoarthritis, degenerative disc disease, spinal stenosis, and sacroiliac joint dysfunction. Unusual causes of low back pain that have been previously identified include abdominal aortic aneurysms, pelvic neoplasms, and retroperitoneal hemorrhages. This report describes a case of back pain that was apparently caused by a duodenal ulcer. A 54-year-old man with no significant medical history presented with a complaint of mid to low back pain (T10-L2), which was diagnosed as joint dysfunction. A comprehensive treatment program was prescribed and the patient was instructed to return to clinic in 4 weeks. Three weeks later, he experienced a syncopal episode followed by coffee ground emesis. He immediately sought medical attention at an emergency room, where he was admitted to the hospital with a diagnosis of upper gastrointestinal bleed. Esophagogastroduodenoscopy showed a large duodenal ulcer, and the patient underwent vagotomy and pyloroplasty. He returned to his physiatrist's office 3 weeks after hospital discharge with minimal back pain. The cause of the back pain proved to be referred visceral pain from his duodenal ulcer. This case is presented to reemphasize the need to include the uncommon phenomena in the differential diagnosis of low back pain.

Inhibition of neutral endopeptidase increases airway responsiveness to ACh in nonsensitized normal rats.

PubMed

Chiba, Y; Misawa, M

1995-02-01

The effects of sensory neuropeptides on the airway responsiveness to acetylcholine (ACh) were investigated in normal nonsensitized rats. The airway responsiveness to inhaled ACh was significantly increased after treatment with neurokinin A (NKA; 0.001%) or substance P (SP; 0.01%) aerosol in the presence of the neutral endopeptidase (NEP) inhibitor. NKA had a more potent effect than SP. Interestingly, the intravenous treatment with NEP inhibitor alone also induced airway hyperresponsiveness (AHR) to inhaled ACh. This AHR was significantly attenuated by pretreatment with a nonselective NK-receptor antagonist, [D-Pro2,D-Trp7,9]SP, systemic capsaicin, or bilateral cervical vagotomy, indicating that decreased NEP activity results in accumulation of endogenous sensory neuropeptide(s) and enhancement of vagal reflex to cause AHR. The airway responsiveness to ACh of isolated left main bronchus was also increased after treatment with 10(-6) M NKA, but not SP, together with 10(-6) M phosphoramidon. This in vitro AHR to ACh induced by phosphoramidon plus NKA was significantly attenuated by pretreatment with 10(-6) M tetrodotoxin. These findings suggest that overaccumulated sensory neuropeptides, especially NKA, may enhance the probability of transmitter release, probably via NK2 receptors, and that the enhanced transmitter release might be involved in AHR in rats.

Ca2+-Dependent Cytoprotective Effects of Ursodeoxycholic and Tauroursodeoxycholic Acid on the Biliary Epithelium in a Rat Model of Cholestasis and Loss of Bile Ducts

PubMed Central

Marzioni, Marco; Francis, Heather; Benedetti, Antonio; Ueno, Yoshiyuki; Fava, Giammarco; Venter, Juliet; Reichenbach, Ramona; Mancino, Maria Grazia; Summers, Ryun; Alpini, Gianfranco; Glaser, Shannon

2006-01-01

Chronic cholestatic liver diseases are characterized by impaired balance between proliferation and death of cholangiocytes, as well as vanishing of bile ducts and liver failure. Ursodeoxycholic acid (UDCA) is a bile acid widely used for the therapy of cholangiopathies. However, little is known of the cytoprotective effects of UDCA on cholangiocytes. Therefore, UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) were administered in vivo to rats simultaneously subjected to bile duct ligation and vagotomy, a model that induces cholestasis and loss of bile ducts by apoptosis of cholangiocytes. Because these two bile acids act through Ca2+ signaling, animals were also treated with BAPTA/AM (an intracellular Ca2+ chelator) or Gö6976 (a Ca2+-dependent protein kinase C-α inhibitor). The administration of UDCA or TUDCA prevented the induction of apoptosis and the loss of proliferative and functional responses observed in the bile duct ligation-vagotomized rats. These effects were neutralized by the simultaneous administration of BAPTA/AM or Gö6976. UDCA and TUDCA enhanced intracellular Ca2+ and IP3 levels, together with increased phosphorylation of protein kinase C-α. Parallel changes were observed regarding the activation of the MAPK and PI3K pathways, changes that were abolished by addition of BAPTA/AM or Gö6976. These studies provide information that may improve the response of cholangiopathies to medical therapy. PMID:16436655

Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

PubMed

Thomas, G R; Thibodeaux, H; Margolius, H S; Webb, J G; Privitera, P J

1987-07-01

The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

Baroreceptors mask sympathetic responses to high intraocular pressure in dogs.

PubMed

Yahagi, Toru; Koyama, Shozo; Osaka, Kazumasa; Koyama, Haruhide

2008-05-30

These experiments were designed to investigate whether increasing intraocular pressure (IOP) in anesthetized dogs produces differential control of sympathetic nerve activities to various organs (heart, kidney, liver, and spleen) and if these sympathetic responses are modified by baroreceptors. We performed simultaneous multi-recordings of cardiac, renal, hepatic and splenic sympathetic nerve activities (CNA, RNA, HNA and SpNA, respectively) during 2 min of increasing IOP to a mean pressure of 30 mmHg. After increasing IOP in dogs with the intact baroreceptors, all of measured nerve activities did not change significantly throughout the experiment. In dogs with denervation of baroreceptors (cervical vagotomy with denervation of the carotid sinus and aortic nerves), only RNA and CNA showed significant increases in response to the increased IOP. However, time course changes in HNA and SpNA did not show any significant differences as compared with the baseline or that of the control group. These results indicate that systemic sympathetic nerve responses to increasing IOP are masked by systemic baroreceptors. As animals were denervated of their systemic baroreceptors, the unidirectional sympathoexcitatory responses to increased IOP were observed on CNA and RNA, but not on HNA and SpNA. These sympathetic outflow, when systemic baroreceptors are impaired as observed in old age, may play an important role in management of glaucoma attack with the use of adrenolytic drugs.

The Vagal Nerve Stimulates Activation of the Hepatic Progenitor Cell Compartment via Muscarinic Acetylcholine Receptor Type 3

PubMed Central

Cassiman, David; Libbrecht, Louis; Sinelli, Nicoletta; Desmet, Valeer; Denef, Carl; Roskams, Tania

2002-01-01

In the rat the hepatic branch of the nervus vagus stimulates proliferation of hepatocytes after partial hepatectomy and growth of bile duct epithelial cells after bile duct ligation. We studied the effect of hepatic vagotomy on the activation of the hepatic progenitor cell compartment in human and rat liver. The number of hepatic progenitor cells and atypical reactive ductular cells in transplanted (denervated) human livers with hepatitis was significantly lower than in innervated matched control livers and the number of oval cells in vagotomized rat livers with galactosamine hepatitis was significantly lower than in livers of sham-operated rats with galactosamine hepatitis. The expression of muscarinic acetylcholine receptors (M1-M5 receptor) was studied by immunohistochemistry and reverse transcriptase-polymerase chain reaction. In human liver, immunoreactivity for M3 receptor was observed in hepatic progenitor cells, atypical reactive ductules, intermediate hepatocyte-like cells, and bile duct epithelial cells. mRNA for the M1-M3 and the M5 receptor, but not the M4 receptor, was detected in human liver homogenates. In conclusion, the hepatic vagus branch stimulates activation of the hepatic progenitor cell compartment in diseased liver, most likely through binding of acetylcholine to the M3 receptor expressed on these cells. These findings may be of clinical importance for patients with a transplant liver. PMID:12163377

The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

PubMed

Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

2014-07-01

It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." © FASEB.

Hypopnea consequent to reduced pulmonary blood flow in the dog.

PubMed

Stremel, R W; Whipp, B J; Casaburi, R; Huntsman, D J; Wasserman, K

1979-06-01

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

PubMed

Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

2012-11-10

Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. Copyright © 2012 Elsevier B.V. All rights reserved.

Nonuniformity in the von Bezold-Jarisch reflex.

PubMed

Salo, Lauren M; Woods, Robyn L; Anderson, Colin R; McAllen, Robin M

2007-08-01

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.

Electroacupuncture improves burn-induced impairment in gastric motility mediated via the vagal mechanism in rats.

PubMed

Song, J; Yin, J; Sallam, H S; Bai, T; Chen, Y; Chen, J D Z

2013-10-01

Delayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns. Male rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24 h post severe burns. (i) Burn delayed GE (P < 0.001). Electroacupuncture improved GE 6 and 24 h post burn (P < 0.001). Vagotomy blocked the EA effect on GE. (ii) Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24 h post burn (P = 0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P = 0.004) and 24 h post burn (P = 0.03, vs sham-EA). (iv) Electroacupuncture attenuated burn-induced increase in plasma IL-6 at both 6 (P = 0.03) and 24 h post burn (P = 0.003). Electroacupuncture at ST-36 improves gastric dysrhythmia and accelerates GE in rats with burns. The improvement seems to be mediated via the vagal pathway involving the inflammatory cytokine IL-6. © 2013 John Wiley & Sons Ltd.

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

PubMed

Sawada, Yoshikazu; Izumida, Yoshihiko; Takeuchi, Yoshinori; Aita, Yuichi; Wada, Nobuhiro; Li, EnXu; Murayama, Yuki; Piao, Xianying; Shikama, Akito; Masuda, Yukari; Nishi-Tatsumi, Makiko; Kubota, Midori; Sekiya, Motohiro; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sugano, Yoko; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yatoh, Shigeru; Suzuki, Hiroaki; Yagyu, Hiroaki; Kawakami, Yasushi; Kadowaki, Takashi; Shimano, Hitoshi; Yahagi, Naoya

2017-11-04

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

Atrial stretch delays gastric emptying of liquids in awake rats.

PubMed

Palheta, R C; Silva, M T B; Barbosa, H L G; Pinheiro, A D N; Cardoso, K V V; Graça, J R V; Magalhães, P J C; Oliveira, R B; Santos, A A

2013-03-21

We previously reported that mechanical atrial stretch (AS) by balloon distention increased gastric tonus in anesthetized rats. The present study evaluated the effect of AS on the gastric emptying of a liquid test meal in awake rats and its underlying neural mechanisms. Anesthetized male rats received a balloon catheter into the right atrium and a gastrostomy cannula. The next day, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and cardiac output (CO) were continuously monitored. After the first 20min of monitoring (basal interval), the balloon was either distended or not (control) with 30, 50, or 70μl saline for 5min. Fifteen minutes later, the rats received the test meal (glucose solution with phenol red), and fractional gastric dye retention was determined 10, 20, or 30min later. Heart rate and CVP values were transiently increased by 50 or 70μl AS but not 30μl AS, whereas gastric emptying was slower after 30, 50, or 70μl AS than after sham distention. Subdiaphragmatic vagotomy or splanchnicotomy+celiac ganglionectomy and capsaicin, ondansetron, hexamethonium, L-NAME, and glibenclamide treatment prevented the AS-induced delay in gastric emptying, whereas atropine and guanethidine treatment failed to prevent it. Atrial stretch inhibited the gastric emptying of liquid via non-adrenergic and non-cholinergic pathways that activate nitric oxide-K(+)ATP channels. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute baroreflex resetting and its control of blood pressure in an open loop model.

PubMed

Tan, W; Panzenbeck, M J; Zucker, I H

1989-01-01

Acute baroreflex resetting has been quantitatively studied in anesthetized dogs. Carotid sinuses were isolated bilaterally and carotid sinus conditioning pressure (CPcsp) was set at nine different levels for 20 min over a range of from 40 to 200 mm Hg. Over this range of 160 mm Hg in CPcsp, the magnitude of baroreflex resetting of set point pressure (Psp), threshold pressure (Pth) and BP50 was 32.0 +/- 5, 43.3 +/- 6 and 39.6 +/- 6 mm Hg, respectively. The extent of resetting was a non-linear function of the level of CPcsp. There is less resetting at high CPcsp. The average extent of resetting is only about 25%. In contrast to this small degree of resetting, a profound inverse relationship between the baseline pressure and the conditioning pressure was observed at the end of the conditioning period for each CPcsp. In addition, we also observed an attenuation in the buffering capacity of the baroreflex at very high or very low CPcsp. Vagotomy and aortic section did not alter baroreflex resetting. This data indicates that the baroreflex is capable of monitoring the absolute level of blood pressure during acute resetting in addition to buffering transient disturbances in arterial pressure. Based upon the results of the present experiments, the concept that acute baroreflex resetting results in an inability of the baroreflex to monitor the absolute level of arterial pressure does not appear to be valid.

Therapeutic management of perforated gastro-duodenal ulcer: literature review.

PubMed

Mouly, C; Chati, R; Scotté, M; Regimbeau, J-M

2013-11-01

Management of perforated gastro-duodenal ulcer (GDU) is not consensual, from no operative treatment to surgery by simple closure, gastrectomy and vagotomy. The purpose of this study is to report results of the literature concerning management of perforated GDU. Two authors, identified in the databases Pubmed and Embase studies, related to the therapeutic management of perforated GDU. The data were extracted from articles published between 1940 and 2012. Non-operative treatment is feasible for patients in good general condition and in good local circumstances without evolved peritonitis with a success rate more than 50%. Simple closure is the standard method. Laparoscopy is a safe and feasible method for patient with delay of treatment less than 24 hours and without associated complications with a success (meaning non conversion) of 80% and a mortality less than 1%. Rate of conversion is 7.9%, and increases in case of ulcer size >6 mm, frail ulcer edges, bleeding associated, unusual location and septic shock. Helicobacter pylori eradication is essential. Gastric tube, abdominal irrigation and drainage are still debated. Two-stage treatment for perforated gastric carcinoma, which represents 10 to 16% of gastric perforation, is a good option for frail patients with resectable tumors. Management of perforated GDU is still a subject of debate without guidelines but with several possibilities of treatment depending of local circumstances of peritonitis and size of defect >20 mm, general conditions, surgeon patterns and experience. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The visceromotor responses to colorectal distension and skin pinch are inhibited by simultaneous jejunal distension.

PubMed

Shafton, Anthony D; Furness, John B; Ferens, Dorota; Bogeski, Goce; Koh, Shir Lin; Lean, Nicholas P; Kitchener, Peter D

2006-07-01

Noxious stimuli that are applied to different somatic sites interact; often one stimulus diminishes the sensation elicited from another site. By contrast, inhibitory interactions between visceral stimuli are not well documented. We investigated the interaction between the effects of noxious distension of the colorectum and noxious stimuli applied to the jejunum, in the rat. Colorectal distension elicited a visceromotor reflex, which was quantified using electromyographic (EMG) recordings from the external oblique muscle of the upper abdomen. The same motor units were activated when a strong pinch was applied to the flank skin. Distension of the jejunum did not provoke an EMG response at this site, but when it was applied during colorectal distension it blocked the EMG response. Jejunal distension also inhibited the response to noxious skin pinch. The inhibition of the visceromotor response to colorectal distension was prevented by local application of tetrodotoxin to the jejunum, and was markedly reduced when nicardipine was infused into the local jejunal circulation. Chronic sub-diaphragmatic vagotomy had no effect on the colorectal distension-induced EMG activity or its inhibition by jejunal distension. The nicotinic antagonist hexamethonium suppressed phasic contractile activity in the jejunum, had only a small effect on the inhibition of visceromotor response by jejunal distension. It is concluded that signals that arise from skin pinch and colorectal distension converge in the central nervous system with pathways that are activated by jejunal spinal afferents; the jejunal signals strongly inhibit the abdominal motor activity evoked by noxious stimuli.

Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels.

PubMed

Mizuno, Masaki; Kamiya, Atsunori; Kawada, Toru; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru

2008-12-01

Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity.

PubMed

Iwasaki, Yusaku; Maejima, Yuko; Suyama, Shigetomo; Yoshida, Masashi; Arai, Takeshi; Katsurada, Kenichi; Kumari, Parmila; Nakabayashi, Hajime; Kakei, Masafumi; Yada, Toshihiko

2015-03-01

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity. Copyright © 2015 the American Physiological Society.

Gastric electrical stimulation with short pulses reduces vomiting but not dysrhythmias in dogs.

PubMed

Chen, Jiande D Z; Qian, Liwei; Ouyang, Hui; Yin, Jieyun

2003-02-01

The aim of this study was to investigate the acute effects of 3 different methods of electrical stimulation in the prevention of vasopressin-induced emetic response and gastric dysrhythmias. Seven female hound dogs chronically implanted with 4 pairs of electrodes on gastric serosa were used in a 5-session study. Saline and vasopressin were infused in sessions 1 and 2, respectively. In the other 3 sessions with vasopressin infusion, 3 different methods of electrical stimulation (short-pulse stimulation, long-pulse stimulation, and electroacupuncture) were applied. Gastric slow waves and vomiting and behaviors suggestive of nausea were recorded in each session. In a separate study, additional experiments were performed in 5 vagotomized dogs to investigate vagally mediated mechanisms. Vasopressin induced gastric dysrhythmias, uncoupling of slow waves, and vomiting and behaviors suggestive of nausea (P < 0.02, analysis of variance). Long-pulse stimulation, but not short-pulse stimulation or electroacupuncture, was capable of preventing vasopressin-induced gastric dysrhythmias and gastric slow wave uncoupling. Short-pulse stimulation and electroacupuncture, but not long-pulse stimulation, prevented vomiting and significantly reduced the symptom scores, which was not noted in the dogs with truncal vagotomy. Long-pulse stimulation normalizes vasopressin-induced slow wave abnormalities with no improvement in vomiting and behaviors suggestive of nausea. Short-pulse stimulation and electroacupuncture prevent vomiting and behaviors suggestive of nausea induced by vasopressin but have no effects on slow waves, and their effects are vagally mediated.

Neuroregulation of a chemosensitive afferent system in the canine distal esophagus.

PubMed

Sandler, A D; Schlegel, J F; DeSautel, M G; Maher, J W

1993-10-01

Systemic and local responses mediated by chemonociceptive receptors located in the mucosa of the canine distal esophagus were examined following stimulation with capsaicin (8-methyl-N-vanillyl-6-nonenamide). The neural pathways and neurotransmitters mediating these sensory responses were also investigated. Topical application of capsaicin solution to the distal esophageal mucosa produced significant increases in lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) (P < 0.01). Pretreatment with tetrodotoxin completely abolished this reflex activity. Following truncal vagotomy and pyloroplasty, topical capsaicin application produced an increase in LESP, but the increases in MAP, PR, and RR were blocked. The initial increase in LESP was blocked by hexamethonium, atropine, and 4-diphenylacetoxy-N-methylpiperidine, but was not inhibited by phentolamine. Excitatory cardiovascular responses were inhibited by hexamethonium. Administration of a Substance P antagonist attenuated both local and systemic responses. These studies suggest that the vagus nerves serve as the primary afferent pathways through which chemonociceptive esophageal stimuli can induce cardiovascular and respiratory reflex excitation. The increase in lower esophageal sphincter pressure in response to mucosal capsaicin stimulation is mediated via an intrinsic neural pathway that functions independently of vagal innervation, but is dependent on both cholinergic ganglionic neurotransmission and muscarinic type 2 smooth muscle receptor excitation. Substance P appears to play a role in primary sensory afferents as a chemonociceptive neurotransmitter in the canine distal esophagus.

Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism.

PubMed

Shin, Andrew C; Zheng, Huiyuan; Berthoud, Hans-Rudolf

2012-02-01

To determine the role of the common hepatic branch of the abdominal vagus on the beneficial effects of Roux-en-Y gastric bypass (RYGB) on weight loss, food intake, food choice, and energy expenditure in a rat model. Although changes in gut hormone patterns are the leading candidates in RYGB's effects on appetite, weight loss, and reversal of diabetes, a potential role for afferent signaling through the vagal hepatic branch potentially sensing glucose levels in the hepatic portal vein has recently been suggested in a mouse model of RYGB. Male Sprague-Dawley rats underwent either RYGB alone (RYGB; n = 7), RYGB + common hepatic branch vagotomy (RYGB + HV; n = 6), or sham procedure (sham; n = 9). Body weight, body composition, meal patterns, food choice, energy expenditure, and fecal energy loss were monitored up to 3 months after intervention. Both RYGB and RYGB + HV significantly reduced body weight, adiposity, meal size, and fat preference, and increased satiety, energy expenditure, and respiratory exchange rate compared with sham procedure, and there were no significant differences in these effects between RYGB and RYGB + HV rats. Integrity of vagal nerve supply to the liver, hepatic portal vein, and the proximal duodenum provided by the common hepatic branch is not necessary for RYGB to reduce food intake and body weight or increase energy expenditure. Specifically, it is unlikely that a hepatic portal vein glucose sensor signaling RYGB-induced increased intestinal gluconeogenesis to the brain depends on vagal afferent fibers.

Bile acid malabsorption in persistent diarrhoea.

PubMed

Smith, M J; Cherian, P; Raju, G S; Dawson, B F; Mahon, S; Bardhan, K D

2000-01-01

We have investigated bile acid malabsorption (BAM), and its response to treatment, in patients seen in this district general hospital with chronic continuous or recurrent diarrhoea. Seven-day retention of 75-SeHCAT was measured (normal: > 10%). Patients were initially given conventional therapy (prednisolone +/- ASA drugs in Crohn's disease, and antidiarrhoeals in the others). If this therapy failed, bile acid sequestrants (BAS) were prescribed. The definition of successful response was based on the patient's perception of sustained improvement. The 304 patients were categorised as follows: Group 1: Crohn's disease patients with ileal resection, in clinical remission (n = 37). Group 2: Crohn's disease, unoperated and in clinical remission (n = 44). Group 3: vagotomy and pyloroplasty, with/without cholecystectomy (n = 26). Group 4: diarrhoea predominant 'irritable bowel syndrome' (IBS) (n = 197). BAM was found in 97% (36/37), 54% (24/44) and 58% (15/26) of patients in groups 1, 2 and 3 respectively. One third (65/197) of patients with IBS had BAM. The outcome of treatment was available in 96 patients with BAM: of the patients with ileal resection 32% responded to antidiarrhoeals, 60% to BAS. Of the unoperated Crohn's patients 55% responded to disease-specific therapy, 40% to BAS. Of the gastric surgery patients 18% responded to conventional treatment, 64% to BAS. Of the IBS patients 15% of responded to conventional therapy, 70% to BAS. This observational study indicates that BAM is common in patients with chronic diarrhoea, and is frequently found in IBS. The results of open treatment suggest that, where antidiarrhoeal drugs fail in such patients, BAS are often effective.

Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus

PubMed Central

The, FO; Cailotto, C; van der Vliet, J; de Jonge, WJ; Bennink, RJ; Buijs, RM; Boeckxstaens, GE

2011-01-01

BACKGROUND AND PURPOSE Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. EXPERIMENTAL APPROACH Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg−1) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. KEY RESULTS Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. CONCLUSIONS AND IMPLICATIONS Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. PMID:21371006

Role of the autonomic nervous system in rat liver regeneration.

PubMed

Xu, Cunshuan; Zhang, Xinsheng; Wang, Gaiping; Chang, Cuifang; Zhang, Lianxing; Cheng, Qiuyan; Lu, Ailing

2011-05-01

To study the regulatory role of autonomic nervous system in rat regenerating liver, surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, then expression profiles of regenerating livers at 2 h after operation were detected using Rat Genome 230 2.0 array. It was shown that the expressions of 97 genes in OC, 230 genes in PH, 253 genes in SPH, 187 genes in VPH, and 177 genes in TDPH were significantly changed in biology. The relevance analysis showed that in SPH, genes involved in stimulus response, immunity response, amino acids and K(+) transport, amino acid catabolism, cell adhesion, cell proliferation mediated by JAK-STAT, Ca(+), and platelet-derived growth factor receptor, cell growth and differentiation through JAK-STAT were up-regulated, while the genes involved in chromatin assembly and disassembly, and cell apoptosis mediated by MAPK were down-regulated. In VPH, the genes associated with chromosome modification-related transcription factor, oxygen transport, and cell apoptosis mediated by MAPK pathway were up-regulated, but the genes associated with amino acid catabolism, histone acetylation-related transcription factor, and cell differentiation mediated by Wnt pathway were down-regulated. In TDPH, the genes related to immunity response, growth and development of regenerating liver, cell growth by MAPK pathway were up-regulated. Our data suggested that splanchnic and vagal nerves could regulate the expressions of liver regeneration-related genes.

Curcumin attenuates collagen-induced inflammatory response through the "gut-brain axis".

PubMed

Dou, Yannong; Luo, Jinque; Wu, Xin; Wei, Zhifeng; Tong, Bei; Yu, Juntao; Wang, Ting; Zhang, Xinyu; Yang, Yan; Yuan, Xusheng; Zhao, Peng; Xia, Yufeng; Hu, Huijuan; Dai, Yue

2018-01-06

Previous studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin. The collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund's adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording. Oral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA. Our results demonstrate that curcumin attenuates CIA through the "gut-brain axis" by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

Effect of YM-14673, an analogue of thyrotropin-releasing hormone, on duodenal bicarbonate secretion in the rat.

PubMed

Takeuchi, K; Niida, H; Ueshima, K; Okabe, S

1991-01-01

The effects of YM-14673, an analogue of thyrotropin-releasing hormone, on duodenal HCO3- secretion were characterized in comparison with those of prostaglandin E2 and carbachol in anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of the perfusate and of the transmucosal potential difference were continuously monitored, and HCO3- output was determined by back-titration of the perfusate and by pH change. YM-14673 (0.1, 0.3 and 1 mg/kg) increased these parameters in a dose-related manner; the total HCO3- output at 1 mg/kg (5.8 +/- 0.7 mumol) was about 50% of that induced by prostaglandin E2 (1 mg/kg, i.v.) and 2 times greater than that induced by carbachol (4 micrograms/kg, i.v.). These responses, induced by YM-14673, were almost completely blocked by bilateral vagotomy and significantly inhibited by atropine (0.3 mg/kg, i.v.) or cyclooxygenase inhibitors, such as indomethacin (5 mg/kg, s.c.) and acetylsalicylic acid (40 mg/kg, s.c.), but not affected by pirenzepine (1 mg/kg, i.v.), a selective M1 antagonist. None of the latter agents had any effect on the HCO3(-)-stimulating action of prostaglandin E2, while the carbachol-induced HCO3- output was significantly reduced by atropine. These results suggest that YM-14673 induces the vagal-dependent HCO3- secretion in the rat duodenum and that this mechanism is mediated by muscarinic cholinoceptors, excluding the M1-subtype, and may involve endogenous prostaglandins.

Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies.

PubMed

Adamu, Mariam Abdullahi; Weck, Melanie Nicole; Gao, Lei; Brenner, Hermann

2010-07-01

Chronic atrophic gastritis (CAG) is an important precursor lesion of intestinal gastric cancer. As it is typically asymptomatic, epidemiological data on the incidence of CAG are sparse. We aimed to provide an overview of published data on CAG incidence (overall and according to risk factors) from follow-up studies. Articles with information on incidence of CAG published in English until 26th of July 2009 were identified through a systematic MEDLINE and EMBASE search. Data extracted include study characteristics and key findings regarding the incidence of CAG. A meta-analysis was performed on the association between Helicobacter pylori infection and CAG incidence. Overall, data on CAG incidence were available from 14 studies, in 7 studies incidence could be estimated according to H. pylori infection. Most studies were conducted in symptomatic or high risk populations and the maximum number of incident cases was 284. Incidence estimates ranged from 0 to 11% per year and were consistently below 1% in patients not infected with H. pylori. The highest incidence was observed in a special study conducted on ulcer patients treated by proximal gastric vagotomy. Rate ratios for the association between H. pylori infection and CAG incidence ranged from 2.4 to 7.6 with a summary estimate of 5.0 (95% confidence interval: 3.1-8.3). Incidence of CAG is very low in the absence of H. pylori infection. There is a need for more population-based studies to provide comparable estimates of incidence and the impact of risk factors in the development of CAG.

Ingestion of dried-bonito broth (dashi) facilitates PV-parvalbumin-immunoreactive neurons in the brain, and affects emotional behaviors in mice.

PubMed

Jargalsaikhan, Undarmaa; Nishimaru, Hiroshi; Matsumoto, Jumpei; Takamura, Yusaku; Nakamura, Tomoya; Hori, Etsuro; Kondoh, Takashi; Ono, Taketoshi; Nishijo, Hisao

2017-12-01

Emerging evidence suggests that traditional diets and nutrition have a significant impact on brain development, and could contribute to the promotion of mental health and prevention of psychiatric disorders in children and adolescents. Moreover, deficits in parvalbumin (PV)-immunoreactive and/or GABAergic neurons are closely associated with various psychiatric disorders in children and adolescents. To investigate the possible neural mechanisms of diet involvement in mental health, we analyzed the effects of dried-bonito dashi (Japanese fish broth) (DBD) on PV-immunoreactive neurons and emotional behaviors in young mice. Male mice after weaning were fed DBD for 60 days, and tested with a resident-intruder test for aggressiveness and a forced swimming test for depression-like symptoms. After the behavioral testing, PV-immunoreactive neurons in the brain were immunohistochemically analyzed. The results indicated that DBD intake decreased aggressiveness and depression-like symptoms, and increased the densities of PV-immunoreactive neurons in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and superior colliculus. These behavioral changes were correlated with the densities of PV-immunoreactive neurons in the mPFC, amygdala, and hippocampus. However, subdiaphragmatic vagotomy did not affect the effects of DBD on emotional behaviors, although it nonspecifically decreased the densities of PV-immunoreactive neurons. The results suggest that DBD might modulate emotional behaviors by promoting PV-immunoreactive and/or GABAergic neuronal activity through parallel routes. The present results highlight a new mechanism for diet involvement in brain functions, and suggest that DBD might have therapeutic potential for the promotion of mental health.

Validation and characterization of a novel method for selective vagal deafferentation of the gut.

PubMed

Diepenbroek, Charlene; Quinn, Danielle; Stephens, Ricky; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; de Lartigue, Guillaume

2017-10-01

There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate models. This method provides improved tissue specificity and superior separation of afferent and efferent signaling compared with vagotomy, capsaicin, and subdiaphragmatic deafferentation. NEW & NOTEWORTHY We develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons. This reliable approach provides superior tissue specificity and selectivity for vagal afferent over efferent targeting than traditional approaches. It can be used to address questions about the role of gut to brain signaling in physiological and pathophysiological conditions. Copyright © 2017 the American Physiological Society.

Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat

PubMed Central

Zhou, Shi-Yi; Lu, Yuan-Xu; Owyang, Chung

2011-01-01

Hyperglycemia has a profound effect on gastric motility. However, little is known about site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg dL−1 had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg dL−1), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10−5 M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT3 antagonist, 0.5 g kg−1) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, NG-nitro-L-arginine methyl ester (l-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia, and in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation. PMID:18356537

Chemoreflex Activity Increases Prostaglandin Endoperoxide Synthase mRNA Expression in the Late-Gestation Fetal Sheep Brain

PubMed Central

Fraites, Melanie J. P.; Wood, Charles E.

2011-01-01

Fetal sheep defend blood pressure, blood volume, and blood gases using baro- and chemoreflexes that influence autonomic and neuroendocrine responses. The local generation of prostanoids within the fetal brain is also an important component in activating hormone responses to these stimuli, but the relationship between the reflexes and prostanoid biosynthesis is unclear. The present study was performed to test the hypothesis that the abundances of prostaglandin biosynthetic enzymes in the fetal brain are dependent upon the activity of the baro- and chemoreflex pathways. We subjected chronically catheterized fetal sheep in late gestation to a 10-minute period of brachiocephalic occlusion (BCO), a stimulus that provokes brisk cardiovascular and neuroendocrine responses. We compared the central nervous system abundance of prostaglandin endoperoxide synthases 1 and 2 (PGHS-1 and PGHS-2) after BCO to (1) fetal sheep that had been subjected to BCO after chronic sinoaortic denervation plus bilateral vagotomy and (2) fetal sheep in which the N-methyl d-aspartate (NMDA) receptor antagonist, ketamine, had been administered prior to BCO. Abundances of messenger RNA (mRNA) for PGHS-1 and of mRNA and protein for PGHS-2 in fetal hippocampus were reduced significantly by either prior denervation or ketamine administration. Prostaglandin endoperoxide synthases 1 and 2 mRNA in pituitary were decreased and increased, respectively, by ketamine pretreatment. The results of this study are consistent with the conclusion that the expression of PGHS-1 and -2 in fetal hippocampus and pituitary are influenced by the baro- and/or chemoreflex pathways within the fetal brain in late gestation. PMID:21846688

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

PubMed

Schulte, Astrid; Lichtenstern, Christoph; Henrich, Michael; Weigand, Markus A; Uhle, Florian

2014-05-15

During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion. Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

PubMed

Wehner, S; Vilz, T O; Sommer, N; Sielecki, T; Hong, G S; Lysson, M; Stoffels, B; Pantelis, D; Kalff, J C

2012-10-01

Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

Reconfiguration of the pontomedullary respiratory network: a computational modeling study with coordinated in vivo experiments.

PubMed

Rybak, I A; O'Connor, R; Ross, A; Shevtsova, N A; Nuding, S C; Segers, L S; Shannon, R; Dick, T E; Dunin-Barkowski, W L; Orem, J M; Solomon, I C; Morris, K F; Lindsey, B G

2008-10-01

A large body of data suggests that the pontine respiratory group (PRG) is involved in respiratory phase-switching and the reconfiguration of the brain stem respiratory network. However, connectivity between the PRG and ventral respiratory column (VRC) in computational models has been largely ad hoc. We developed a network model with PRG-VRC connectivity inferred from coordinated in vivo experiments. Neurons were modeled in the "integrate-and-fire" style; some neurons had pacemaker properties derived from the model of Breen et al. We recapitulated earlier modeling results, including reproduction of activity profiles of different respiratory neurons and motor outputs, and their changes under different conditions (vagotomy, pontine lesions, etc.). The model also reproduced characteristic changes in neuronal and motor patterns observed in vivo during fictive cough and during hypoxia in non-rapid eye movement sleep. Our simulations suggested possible mechanisms for respiratory pattern reorganization during these behaviors. The model predicted that network- and pacemaker-generated rhythms could be co-expressed during the transition from gasping to eupnea, producing a combined "burst-ramp" pattern of phrenic discharges. To test this prediction, phrenic activity and multiple single neuron spike trains were monitored in vagotomized, decerebrate, immobilized, thoracotomized, and artificially ventilated cats during hypoxia and recovery. In most experiments, phrenic discharge patterns during recovery from hypoxia were similar to those predicted by the model. We conclude that under certain conditions, e.g., during recovery from severe brain hypoxia, components of a distributed network activity present during eupnea can be co-expressed with gasp patterns generated by a distinct, functionally "simplified" mechanism.

[[Development of Surgical Gastroenterology in Prikamye].

PubMed

Palatova, L F; Nechaev, O I

2016-01-01

To present the history of surgical gastroenterology in Perm krai. Narrative, historical, genetic, comparative and structural. In the early 20th century the main method of surgical treatment of peptic ulcer was gastroenteroanastomosis. A significant number of recurrences resulted to distal gastrectomy implementation in the 30s in the Clinic of hospital surgery of Perm medical institute, led by professor M.V. Shats. It was also performed in major cities of the region: Lysva, Kungur, Berezniki, Kizel, Osa. Treatment of ulcer perforation and bleeding was accomplished at the department of surgical diseases of pediatric faculty, led by Professor V. N. Repin. He also developed vagotomy and methods of diagnostics and treatment of diseases of operated stomach. Comorbidity was also researched. The combination of liver and biliary tract diseases was re- searched in the Hospital surgical clinic of Perm, initially led by Professor S. Yu. Minkin and then by academician E. A. Wagner (L. F. Palatova). The results of surgical treatment of cholelithiasis, depending on morphological and biochemical abnormali- ties in liver and chemical composition of gallstones were studied (L. P. Kotelnikova). Indications for surgery in cholelithiasis in conjunction with pathology of stomach, duodenum and liver were defined (A.V. Popov). The results of surgical treatment of biliary pancreatitis and cholangitis (L. B. Guschensky), and diseases of stomach, duodenum and pancreas with cholelithiasis were obtained (D.V. Shvarev). The priority trends of research of Perm scientists were treatment of post-resection syndrome, arteriomesen- terial obstruction, pathogenesis of gallstone disease and its combination with other disorders of the digestive system.

Cardiorespiratory action of opioid/tachykinin agonist peptide hybrid in anaesthetized rats: Transduction pathways.

PubMed

Wojciechowski, Piotr; Szereda-Przestaszewska, Małgorzata; Lipkowski, Andrzej Wojciech

2017-09-05

AWL3106 composed of opioid (dermorphin) and tachykinin (substance P 7-11 ) pharmacophores is a new compound with high analgesic potency and markedly reduced ability to induce tolerance and dependence. The present study aimed to determine the respiratory and cardiovascular responses evoked by this peptide in urethane-chloralose anaesthetized, spontaneously breathing rats in the presence or absence of vagal connection. Intravenous injection of AWL3106 at a dose of 0.3μmol/kg in intact rats resulted in apnoea lasting 5.1 ± 0.7s. Breathing that followed was of diminished frequency (F) and augmented tidal volume (V T ) with no significant impact on minute ventilation. AWL3106-challenge induced biphasic fall in arterial blood pressure with no effect on heart rate. Midcervical and supranodosal sectioning the vagal nerves prevented the occurrence of the apnoea and abrogated the post-AWL3106 reduction in F but failed to eliminate the increase in V T . Hypotensive response appeared to be less profound following supranodose vagotomy. NaloxoneHCl abolished solely the occurrence of apnoea. However additional blockade of tachykinin NK 1 receptors with SR140333 was required to abolish V T increase, deceleration of breathing and to markedly suppress AWL3106-induced hypotension. The present study shows that extravagally controlled stimulation of V T maintains fairly regular ventilation by levelling the bradypnoeic effects. Although the peptide showed no cardiac effects, hypotension occurring beyond the vagal loop may limit future therapeutic benefits of this chimeric compound. Copyright © 2017 Elsevier B.V. All rights reserved.

[Comparative study on the reflex responses of carotid and aortic baroreceptors in the rabbit].

PubMed

Li, Z; Ho, S Y

1989-08-01

In 81 anesthetized rabbits, the baroreflex control of heart rate (HR), hind-limb vascular resistance (HVR) and renal sympathetic nerve activity (RSNA) was observed during arterial baroreceptor loading and unloading by intravenously injecting phenylephrine (PE) and nitroprusside (NP). The results were as follows: (1) An increase of arterial pressure with PE caused reduction in HR, HVR and RSNA, while a decrease of arterial pressure with NP evoked opposite responses. These reflex responses were reproducible. (2) By either carotid baroreceptor denervation (CBRX) or aortic baroreceptor denervation (ABRX), the reflex changes of HR induced by injecting PE and NP were impaired (P less than 0.01), while the reflex responses in HVP remained unchanged. Despite of the enhanced basal RSNA following ABRX or CBRX, the magnitude of reflex inhibition in RSNA during injecting NP was similar to that before denervation, whereas that of the reflex excitation in RSNA during injecting NP was reduced (P less than 0.05). (3) After complete sino-aortic denervation (SAD), the change of arterial pressure following PE or NP injection was enhanced, but the reflex changes in HR, HVR and RSNA were significantly diminished (P less than 0.001). (4) Vagotomy abolished the residual reflex changes observed after SAD. The results indicate that the aortic and carotid baroreceptors may regulate HR in a simple additive manner, while the aortic baroreceptor seems to be more important. Furthermore, both the aortic and carotid baroreceptors may play important roles for the reflex control of HVR and RSNA, and operate mutually by the way of inhibitory summation.

Respiratory effects of cigarette smoke, dust, and histamine in newborn rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trippenbach, T.; Kelly, G.

1988-02-01

We studied the respiratory effects of cigarette smoke, 5% histamine aerosol, and dust in unanesthetized 1- to 7-day-old rabbits in a body plethysmograph. Cigarette smoke immediately provoked the animal's arousal and irregular breathing. Histamine and dust had no effect in some of the youngest animals. In others, 5-15 s from the onset of the exposure to either of the two stimuli, respiratory rate increased and the depth of breathing decreased. These changes were more pronounced with age. The fact that effects of dust and aerosol lessened with time of exposure showed adaptation to the stimuli. The age dependence of themore » reflex response was also observed after injection of 50 micrograms of histamine per kilogram into the external jugular vein in anesthetized (50 mg ketamine + 3 mg acepromazine per kg) and tracheostomized rabbits during the 1st wk of life. In 1-day-old animals, a short-lasting excitation was followed by apnea or a prolongation of expiratory phase. Peak amplitude of the diaphragmatic EMG (EMGdi) increased in all animals, but only in the youngest was the EMGdi increase paralleled by an increase in tidal volume. In vagotomized animals or animals pretreated with H1-blocker, histamine never affected timing parameters in animals greater than 1 day old. In the youngest animals, respiratory depression due to histamine was not abolished after vagotomy or promethazine. The results imply that inputs from the upper airways and the rapidly adapting pulmonary mechanoreceptors exert their effects on the pattern of breathing immediately after birth in rabbits. The importance of those inputs increases with maturation.« less

Mediobasal Hypothalamic SIRT1 Is Essential for Resveratrol’s Effects on Insulin Action in Rats

PubMed Central

Knight, Colette M.; Gutierrez-Juarez, Roger; Lam, Tony K.T.; Arrieta-Cruz, Isabel; Huang, Loli; Schwartz, Gary; Barzilai, Nir; Rossetti, Luciano

2011-01-01

OBJECTIVE Sirtuin 1 (SIRT1) and its activator resveratrol are emerging as major regulators of metabolic processes. We investigate the site of resveratrol action on glucose metabolism and the contribution of SIRT1 to these effects. Because the arcuate nucleus in the mediobasal hypothalamus (MBH) plays a pivotal role in integrating peripheral metabolic responses to nutrients and hormones, we examined whether the actions of resveratrol are mediated at the MBH. RESEARCH DESIGN AND METHODS Sprague Dawley (SD) male rats received acute central (MBH) or systemic injections of vehicle, resveratrol, or SIRT1 inhibitor during basal pancreatic insulin clamp studies. To delineate the pathway(s) by which MBH resveratrol modulates hepatic glucose production, we silenced hypothalamic SIRT1 expression using a short hairpin RNA (shRNA) inhibited the hypothalamic ATP-sensitive potassium (KATP) channel with glibenclamide, or selectively transected the hepatic branch of the vagus nerve while infusing resveratrol centrally. RESULTS Our studies show that marked improvement in insulin sensitivity can be elicited by acute administration of resveratrol to the MBH or during acute systemic administration. Selective inhibition of hypothalamic SIRT1 using a cell-permeable SIRT1 inhibitor or SIRT1-shRNA negated the effect of central and peripheral resveratrol on glucose production. Blockade of the KATP channel and hepatic vagotomy significantly attenuated the effect of central resveratrol on hepatic glucose production. In addition, we found no evidence for hypothalamic AMPK activation after MBH resveratrol administration. CONCLUSIONS Taken together, these studies demonstrate that resveratrol improves glucose homeostasis mainly through a central SIRT1-dependent pathway and that the MBH is a major site of resveratrol action. PMID:21896928

The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.

PubMed

Bercik, P; Park, A J; Sinclair, D; Khoshdel, A; Lu, J; Huang, X; Deng, Y; Blennerhassett, P A; Fahnestock, M; Moine, D; Berger, B; Huizinga, J D; Kunze, W; McLean, P G; Bergonzelli, G E; Collins, S M; Verdu, E F

2011-12-01

The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system. © 2011 Blackwell Publishing Ltd.

Vagus nerve contributes to the development of steatohepatitis and obesity in phosphatidylethanolamine N-methyltransferase deficient mice.

PubMed

Gao, Xia; van der Veen, Jelske N; Zhu, Linfu; Chaba, Todd; Ordoñez, Marta; Lingrell, Susanne; Koonen, Debby P Y; Dyck, Jason R B; Gomez-Muñoz, Antonio; Vance, Dennis E; Jacobs, René L

2015-04-01

Phosphatidylethanolamine N-methyltransferase (PEMT), a liver enriched enzyme, is responsible for approximately one third of hepatic phosphatidylcholine biosynthesis. When fed a high-fat diet (HFD), Pemt(-/-) mice are protected from HF-induced obesity; however, they develop steatohepatitis. The vagus nerve relays signals between liver and brain that regulate peripheral adiposity and pancreas function. Here we explore a possible role of the hepatic branch of the vagus nerve in the development of diet induced obesity and steatohepatitis in Pemt(-/-) mice. 8-week old Pemt(-/-) and Pemt(+/+) mice were subjected to hepatic vagotomy (HV) or capsaicin treatment, which selectively disrupts afferent nerves, and were compared to sham-operated or vehicle-treatment, respectively. After surgery, mice were fed a HFD for 10 weeks. HV abolished the protection against the HFD-induced obesity and glucose intolerance in Pemt(-/-) mice. HV normalized phospholipid content and prevented steatohepatitis in Pemt(-/-) mice. Moreover, HV increased the hepatic anti-inflammatory cytokine interleukin-10, reduced chemokine monocyte chemotactic protein-1 and the ER stress marker C/EBP homologous protein. Furthermore, HV normalized the expression of mitochondrial electron transport chain proteins and of proteins involved in fatty acid synthesis, acetyl-CoA carboxylase and fatty acid synthase in Pemt(-/-) mice. However, disruption of the hepatic afferent vagus nerve by capsaicin failed to reverse either the protection against the HFD-induced obesity or the development of HF-induced steatohepatitis in Pemt(-/-) mice. Neuronal signals via the hepatic vagus nerve contribute to the development of steatohepatitis and protection against obesity in HFD fed Pemt(-/-) mice. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus.

PubMed

The, Fo; Cailotto, C; van der Vliet, J; de Jonge, W J; Bennink, R J; Buijs, R M; Boeckxstaens, G E

2011-07-01

Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg(-1) ) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Role of the vagal afferents in substance P-induced respiratory responses in anaesthetized rabbits.

PubMed

Prabhakar, N R; Runold, M; Yamamoto, Y; Lagercrantz, H; Cherniack, N S; von Euler, C

1987-09-01

Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit.

PubMed

Li, Zhuang; Yi, Chun-Xia; Katiraei, Saeed; Kooijman, Sander; Zhou, Enchen; Chung, Chih Kit; Gao, Yuanqing; van den Heuvel, José K; Meijer, Onno C; Berbée, Jimmy F P; Heijink, Marieke; Giera, Martin; Willems van Dijk, Ko; Groen, Albert K; Rensen, Patrick C N; Wang, Yanan

2017-11-03

Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate. Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice. Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT. Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Stimulation of gastric bicarbonate secretion by an analog of thyrotropin-releasing hormone, YM-14673, in the rat.

PubMed

Takeuchi, K; Ueshima, K; Okabe, S

1991-03-01

The effects of YM-14673, a thyrotropin-releasing hormone analog, on gastric alkaline secretion were investigated in the anesthetized rat pretreated with omeprazole (60 mg/kg, intraperitoneally) by measuring the luminal pH, transmucosal PD and HCO3- output. The whole stomach was perfused at a flow rate of 0.7 ml/min with saline (pH 4.5) in the absence of acid secretion, the pH of the perfusate and PD were continuously monitored and the HCO3- output was measured as acid-neutralizing capacity by back-titration of the perfusate to pH 4.5. YM-14673, given intravenously at the doses (0.1-1 mg/kg) that stimulated acid secretion, increased the pH and HCO3- output in a dose-dependent fashion, but did not significantly affect the PD. Prostaglandin E2 (1 mg/kg) elevated the pH and HCO3- output with concomitant decrease in the PD, whereas carbachol (4 micrograms/kg), similar to YM-14673, produced an increase of the pH and HCO3- output with no change in the PD. The net HCO3- output (4.3 +/- 0.3 muEq) induced by 0.3 mg/kg of YM-14673 was about 60 and 150% of that induced by prostaglandin E2 and carbachol, respectively. The increased pH and HCO3- responses caused by YM-14673 were almost completely abolished by vagotomy, significantly inhibited by atropine (0.3 mg/kg, intravenously) and indomethacin (5 mg/kg, subcutaneously) but not affected by pirenzepine (1 mg/kg, intravenously). These results suggest that YM-14673, a thyrotropin-releasing hormone analog, produced vagally mediated HCO3- secretion in the rat stomach, and the mechanism may involve the cholinergic system, which is mediated with muscarinic M2 receptors and interacts with endogenous prostaglandins.

Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve.

PubMed

Uemura, Norihito; Yagi, Hisashi; Uemura, Maiko T; Hatanaka, Yusuke; Yamakado, Hodaka; Takahashi, Ryosuke

2018-05-11

Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson's disease (PD). Braak's hypothesis based on autopsy studies suggests that Lewy pathology initially occurs in the enteric nervous system (ENS) and then travels retrogradely to the dorsal motor nucleus of the vagus nerve (dmX), proceeding from there in a caudo-rostral direction. Recent evidence that α-Syn aggregates propagate between interconnected neurons supports this hypothesis. However, there is no direct evidence demonstrating this transmission from the ENS to the dmX and then to the SNpc. We inoculated α-Syn preformed fibrils (PFFs) or phosphate-buffered saline (PBS) into the mouse gastric wall and analyzed the progression of the pathology. The mice inoculated with α-Syn PFFs, but not with PBS, developed phosphorylated α-Syn (p-α-Syn)-positive LB-like aggregates in the dmX at 45 days postinoculation. This aggregate formation was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs, suggesting that the aggregates in the dmX were retrogradely induced via the vagus nerve. Unexpectedly, the number of neurons containing p-α-Syn-positive aggregates in the dmX decreased over time, and no further caudo-rostral propagation beyond the dmX was observed up to 12 months postinoculation. P-α-Syn-positive aggregates were also present in the myenteric plexus at 12 months postinoculation. However, unlike in patients with PD, there was no cell-type specificity in neurons containing those aggregates in this model. These results indicate that α-Syn PFF inoculation into the mouse gastrointestinal tract can induce α-Syn pathology resembling that of very early PD, but other factors are apparently required if further progression of PD pathology is to be replicated in this animal model.

Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

PubMed Central

Liang, Chang-seng; Huckabee, William E.

1973-01-01

When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

PubMed

Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

2012-04-01

The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

PubMed

Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

2016-07-01

Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity. © 2016 Society for Endocrinology.

Dual autonomic inhibitory action of central Apelin on gastric motor functions in rats.

PubMed

Bülbül, Mehmet; Sinen, Osman

2018-07-01

Centrally administered apelin has been shown to inhibit gastric emptying (GE) in rodents, however, the relevant mechanism has been investigated incompletely. Using male Wistar rats, we investigated the efferent pathways involved in gastroinhibitory action of central apelin. Stereotaxic intracerebroventricular (icv) cannulation, subdiaphragmatic vagotomy (VGX) and/or celiac ganglionectomy (CGX) were performed 7 days prior to the experiments. Apelin-13 was administered (30 nmol, icv) 90 min prior to GE measurement. Nitric oxide synthase inhibitor L-NAME (100 mg/kg), sympatholytic agent guanethidine (5 mg/kg) and/or muscarinic receptor agonist bethanechol (1 mg/kg) were administered intraperitoneally 30 min prior to the central apelin-13 injection. Two strain gages were implanted serosally onto antrum and pylorus to monitor gastric postprandial motility. Heart rate variability (HRV) analysis was performed before and after central vehicle or apelin-13 administration. Apelin-13 delayed solid GE significantly by disturbing coordinated antral and pyloric postprandial contractions. The apelin-induced delayed GE was attenuated partially by CGX or VGX, whereas it was restored completely in rats underwent both CGX and VGX. L-NAME did not change the apelin-induced alterations. Guanethidine or bethanechol restored the apelin-induced gastroinhibition partially, while it was abolished completely in rats received both agents. Apelin-13 decreased the HRV spectral activity in high-frequency range by increasing low-frequency component and the ratio of LF:HF. The present data suggest that (1) both vagal parasympathetic and sympathetic pathways play a role in apelin-induced gastroinhibition, (2) central apelin attenuates vagal cholinergic pathway rather than activating nonadrenergic-noncholinergic pathway. Apelin/APJ receptor system might be candidate for the treatment of autonomic dysfunction and gastrointestinal motor disorders. Copyright © 2018 Elsevier B.V. All

Cardiovascular effects of the essential oil of Alpinia zerumbet leaves and its main constituent, Terpinen-4-ol, in rats: role of the autonomic nervous system.

PubMed

Lahlou, Saad; Galindo, Charles Antonio Barros; Leal-Cardoso, José Henrique; Fonteles, Manassés Claudino; Duarte, Gloria Pinto

2002-12-01

Cardiovascular effects of intravenous ( i. v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) were investigated in rats. Additionally this study examined (I) whether the autonomic nervous system is involved in the mediation of EOAZ-induced changes in mean aortic pressure (MAP) and heart rate (HR), and (II) whether these changes could be, at least in part, attributed to the actions of terpinen-4-ol (Trp-4-ol), the major constituent of EOAZ. In both pentobarbitone-anaesthetised and conscious rats, i. v. bolus injections of EOAZ (1 to 20 mg/kg) elicited immediate and dose-dependent decreases in MAP. In anaesthetised rats, EOAZ decreased HR only at higher doses (10 and 20 mg/kg), while changes of this parameter were not uniform in conscious rats. Hypotensive responses to EOAZ were of the same order of magnitude or duration, irrespective of whether the animal was under general anaesthesia. Pretreatment of anaesthetised rats with bilateral vagotomy did not modify significantly the hypotensive and bradycardic responses to EOAZ. In conscious rats, i. v. injections of bolus doses (1 to 10 mg/kg) of Trp-4-ol also elicited immediate and dose-dependent decreases in MAP. However, these hypotensive effects were significantly greater than those evoked by the same doses of EOAZ (1 to 10 mg/kg). Intravenous pretreatment of conscious rats with either methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) had no significant effects on the EOAZ-induced hypotension. These data show that i. v. treatment with the EOAZ in either anaesthetised or conscious rats induced an immediate and significant hypotension, an effect that could be partially attributed to the actions of Trp-4-ol. The hypotension appears independent of the presence of an operational sympathetic nervous system, suggesting that the EOAZ may be a direct vasorelaxant agent.

Body temperature depression and peripheral heat loss accompany the metabolic and ventilatory responses to hypoxia in low and high altitude birds.

PubMed

Scott, Graham R; Cadena, Viviana; Tattersall, Glenn J; Milsom, William K

2008-04-01

The objectives of this study were to compare the thermoregulatory, metabolic and ventilatory responses to hypoxia of the high altitude bar-headed goose with low altitude waterfowl. All birds were found to reduce body temperature (T(b)) during hypoxia, by up to 1-1.5 degrees C in severe hypoxia. During prolonged hypoxia, T(b) stabilized at a new lower temperature. A regulated increase in heat loss contributed to T(b) depression as reflected by increases in bill surface temperatures (up to 5 degrees C) during hypoxia. Bill warming required peripheral chemoreceptor inputs, since vagotomy abolished this response to hypoxia. T(b) depression could still occur without bill warming, however, because vagotomized birds reduced T(b) as much as intact birds. Compared to both greylag geese and pekin ducks, bar-headed geese required more severe hypoxia to initiate T(b) depression and heat loss from the bill. However, when T(b) depression or bill warming were expressed relative to arterial O(2) concentration (rather than inspired O(2)) all species were similar; this suggests that enhanced O(2) loading, rather than differences in thermoregulatory control centres, reduces T(b) depression during hypoxia in bar-headed geese. Correspondingly, bar-headed geese maintained higher rates of metabolism during severe hypoxia (7% inspired O(2)), but this was only partly due to differences in T(b). Time domains of the hypoxic ventilatory response also appeared to differ between bar-headed geese and low altitude species. Overall, our results suggest that birds can adjust peripheral heat dissipation to facilitate T(b) depression during hypoxia, and that bar-headed geese minimize T(b) and metabolic depression as a result of evolutionary adaptations that enhance O(2) transport.

Neural control of ventilation prevents both over-distension and de-recruitment of experimentally injured lungs.

PubMed

Brander, Lukas; Moerer, Onnen; Hedenstierna, Göran; Beck, Jennifer; Takala, Jukka; Slutsky, Arthur S; Sinderby, Christer

2017-03-01

Endogenous pulmonary reflexes may protect the lungs during mechanical ventilation. We aimed to assess integration of continuous neurally adjusted ventilatory assist (cNAVA), delivering assist in proportion to diaphragm's electrical activity during inspiration and expiration, and Hering-Breuer inflation and deflation reflexes on lung recruitment, distension, and aeration before and after acute lung injury (ALI). In 7 anesthetised rabbits with bilateral pneumothoraces, we identified adequate cNAVA level (cNAVA AL ) at the plateau in peak ventilator pressure during titration procedures before (healthy lungs with endotracheal tube, [HL ETT ]) and after ALI (endotracheal tube [ALI ETT ] and during non-invasive ventilation [ALI NIV ]). Following titration, cNAVA AL was maintained for 5min. In 2 rabbits, procedures were repeated after vagotomy (ALI ETT+VAG ). In 3 rabbits delivery of assist was temporarily modulated to provide assist on inspiration only. Computed tomography was performed before intubation, before ALI, during cNAVA titration, and after maintenance at cNAVA AL . During ALI ETT and ALI NIV , normally aerated lung-regions doubled and poorly aerated lung-regions decreased to less than a third (p<0.05) compared to HL ETT ; no over-distension was observed. Tidal volumes were<5ml/kg throughout. Removing assist during expiration resulted in lung de-recruitment during ALI ETT , but not during ALI NIV . During ALI ETT+VAG the expiratory portion of EAdi disappeared, resulting in cyclic lung collapse and recruitment. When using cNAVA in ALI, vagally mediated reflexes regulated lung recruitment preventing both lung over-distension and atelectasis. During non-invasive cNAVA the upper airway muscles play a role in preventing atelectasis. Future studies should be performed to compare these findings with conventional lung-protective approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

Nucleus Ambiguus Cholinergic Neurons Activated by Acupuncture: Relation to Enkephalin

PubMed Central

Guo, Zhi-Ling; Li, Min; Longhurst, John C.

2012-01-01

Acupuncture regulates autonomic function. Our previous studies have shown that electroacupuncture (EA) at the Jianshi–Neiguan acupoints (P5–P6, underlying the median nerve) inhibits central sympathetic outflow and attenuates excitatory cardiovascular reflexes, in part, through an opioid mechanism. It is unknown if EA at these acupoints influences the parasympathetic system. Thus, using c-Fos expression, we examined activation of nucleus ambiguus (NAmb) neurons by EA, their relation to cholinergic (preganglionic parasympathetic) neurons and those containing enkephalin. To enhance detection of cell bodies containing enkephalin, colchicine (90–100 μg/kg) was administered into the subarachnoid space of cats 30 hr prior to EA or sham-operated controls for EA. Following bilateral barodenervation and cervical vagotomy, either EA for 30 min at P5–P6 acupoints or control stimulation (needle placement at P5–P6 without stimulation) was applied. While perikarya containing enkephalin were observed in some medullary nuclei (e.g., râphe), only enkephalin-containing neuronal processes were found in the NAmb. Compared to controls (n=4), more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin was noted in the NAmb of EA-treated cats (n=5; P<0.01). Moreover, neurons double-labeled with c-Fos and choline acetyltransferase in the NAmb were identified in EA-treated, but not the control animals. These data demonstrate for the first time that EA activates preganglionic parasympathetic neurons in the NAmb. Because of their close proximity, these EA-activated neurons likely interact with nerve fibers containing enkephalin. These results suggest that EA at the P5–P6 acupoints has the potential to influence parasympathetic outflow and cardiovascular function, likely through an enkephalinergic mechanism. PMID:22306033

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

PubMed

Khasar, S G; Reichling, D B; Green, P G; Isenberg, W M; Levine, J D

2003-01-01

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control

Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in mice.

PubMed

The, Frans O; Boeckxstaens, Guy E; Snoek, Susanne A; Cash, Jenna L; Bennink, Roel; Larosa, Gregory J; van den Wijngaard, Rene M; Greaves, David R; de Jonge, Wouter J

2007-10-01

We previously showed that intestinal inflammation is reduced by electrical stimulation of the efferent vagus nerve, which prevents postoperative ileus in mice. We propose that this cholinergic anti-inflammatory pathway is mediated via alpha7 nicotinic acetylcholine receptors expressed on macrophages. The aim of this study was to evaluate pharmacologic activation of the cholinergic anti-inflammatory pathway in a mouse model for postoperative ileus using the alpha7 nicotinic acetylcholine receptor-agonist AR-R17779. Mice were pretreated with vehicle, nicotine, or AR-R17779 20 minutes before a laparotomy (L) or intestinal manipulation (IM). Twenty-four hours thereafter gastric emptying was determined using scintigraphy and intestinal muscle inflammation was quantified. Nuclear factor-kappaB transcriptional activity and cytokine production was assayed in peritoneal macrophages. Twenty-four hours after surgery IM led to a delayed gastric emptying compared with L (gastric retention: L(saline) 14% +/- 4% vs IM(saline) 38% +/- 10%, P = .04). Pretreatment with AR-R17779 prevented delayed gastric emptying (IM(AR-R17779) 15% +/- 4%, P = .03). IM elicited inflammatory cell recruitment (L(saline) 50 +/- 8 vs IM(saline) 434 +/- 71 cells/mm(2), P = .001) which was reduced by AR-R17779 pretreatment (IM(AR-R17779) 231 +/- 32 cells/mm(2), P = .04). An equimolar dose of nicotine was not tolerated. Subdiaphragmal vagotomy did not affect the anti-inflammatory properties of AR-R17779. In peritoneal macrophages, both nicotinic agonists reduced nuclear factor kappaB transcriptional activity and proinflammatory cytokine production, with nicotine being more effective than AR-R17779. AR-R17779 treatment potently prevents postoperative ileus, whereas toxicity limits nicotine administration to ineffective doses. Our data further imply that nicotinic inhibition of macrophage activation may involve other receptors in addition to alpha7 nicotinic acetylcholine receptor.

Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity.

PubMed

Oikawa, Shino; Kai, Yuko; Tsuda, Masayuki; Ohata, Hisayuki; Mano, Asuka; Mizoguchi, Naoko; Sugama, Shuei; Nemoto, Takahiro; Suzuki, Kenji; Kurabayashi, Atsushi; Muramoto, Kazuyo; Kaneda, Makoto; Kakinuma, Yoshihiko

2016-11-01

We previously developed cardiac ventricle-specific choline acetyltransferase (ChAT) gene-overexpressing transgenic mice (ChAT tgm), i.e. an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS). By using this murine model, we determined that this system was responsible for characteristics of resistance to ischaemia, or hypoxia, via the modulation of cellular energy metabolism and angiogenesis. In line with our previous study, neuronal ChAT-immunoreactivity in the ChAT tgm brains was not altered from that in the wild-type (WT) mice brains; in contrast, the ChAT tgm hearts were the organs with the highest expression of the ChAT transgene. ChAT tgm showed specific traits in a central nervous system (CNS) phenotype, including decreased response to restraint stress, less depressive-like and anxiety-like behaviours and anti-convulsive effects, all of which may benefit the heart. These phenotypes, induced by the activation of cardiac NNCCS, were dependent on the vagus nerve, because vagus nerve stimulation (VS) in WT mice also evoked phenotypes similar to those of ChAT tgm, which display higher vagus nerve discharge frequency; in contrast, lateral vagotomy attenuated these traits in ChAT tgm to levels observed in WT mice. Furthermore, ChAT tgm induced several biomarkers of VS responsible for anti-convulsive and anti-depressive-like effects. These results suggest that the augmentation of the NNCCS transduces an effective and beneficial signal to the afferent pathway, which mimics VS. Therefore, the present study supports our hypothesis that activation of the NNCCS modifies CNS to a more stress-resistant state through vagus nerve activity. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Altered respiratory response to substance P in capsaicin-treated rats.

PubMed

Towle, A C; Mueller, R A; Breese, G R; Lauder, J

1985-01-01

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothane-anesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaCO2 equal to and PaO2 greater than vehicle injected controls. In addition, the minute ventilation-PaCO2 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaCO2 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent. The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaCO2 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaCO2 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin. These results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.

Substance P receptor blockade decreases stretch-induced lung cytokines and lung injury in rats.

PubMed

Brégeon, Fabienne; Steinberg, Jean Guillaume; Andreotti, Nicolas; Sabatier, Jean-Marc; Delpierre, Stéphane; Ravailhe, Sylvie; Jammes, Yves

2010-04-15

Overdistension of lung tissue during mechanical ventilation causes cytokine release, which may be facilitated by the autonomic nervous system. We used mechanical ventilation to cause lung injury in rats, and studied how cervical section of the vagus nerve, or substance P (SP) antagonism, affected the injury. The effects of 40 or 25 cmH(2)O high airway pressure injurious ventilation (HV(40) and HV(25)) were studied and compared with low airway pressure ventilation (LV) and spontaneous breathing (controls). Lung mechanics, lung weight, gas exchange, lung myeloperoxidase activity, lung concentrations of interleukin (IL)-1 beta and IL-6, and amounts of lung SP were measured. Control rats were intact, others were bivagotomized, and in some animals we administered the neurokinin-1 (NK-1) receptor blocking agent SR140333. We first determined the durations of HV(40) and HV(25) that induced the same levels of lung injury and increased lung contents of IL-1 beta and IL-6. They were 90 min and 120 min, respectively. Both HV(40) and HV(25) increased lung SP, IL-1 beta and IL-6 levels, these effects being markedly reduced by NK-1 receptor blockade. Bivagotomy reduced to a lesser extent the HV(40)- and HV(25)-induced increases in SP but significantly reduced cytokine production. Neither vagotomy nor NK-1 receptor blockade prevented HV(40)-induced lung injury but, in the HV(25) group, they made it possible to maintain lung injury indices close to those measured in the LV group. This study suggests that both neuronal and extra-neuronal SP might be involved in ventilator-induced lung inflammation and injury. NK-1 receptor blockade could be a pharmacological tool to minimize some adverse effects of mechanical ventilation.

Role of neurotensin and opioid receptors in the cardiorespiratory effects of [Ile⁹]PK20, a novel antinociceptive chimeric peptide.

PubMed

Kaczyńska, Katarzyna; Szereda-Przestaszewska, Małgorzata; Kleczkowska, Patrycja; Lipkowski, Andrzej W

2014-10-15

Ile(9)PK20 is a novel hybrid of opioid-neurotensin peptides synthesized from the C-terminal hexapeptide of neurotensin and endomorphin-2 pharmacophore. This chimeric compound shows potent central and peripheral antinociceptive activity in experimental animals, however nothing is known about its influence on the respiratory and cardiovascular parameters. The present study was designed to determine the cardiorespiratory effects exerted by an intravenous injection (i.v.) of [Ile(9)]PK20. Share of the vagal afferentation and the contribution of NTS1 neurotensin and opioid receptors were tested. Intravenous injection of the hybrid at a dose of 100 μg/kg in the intact, anaesthetized rats provoked an increase in tidal volume preceded by a prompt short-lived decrease. Immediately after the end of injection brief acceleration of the respiratory rhythm appeared, and was ensued by the slowing down of breathing. Changes in respiration were concomitant with a bi-phasic response of the blood pressure: an immediate increase was followed by a sustained hypotension. Midcervical vagotomy eliminated the increase in tidal volume and respiratory rate responses. Antagonist of opioid receptors - naloxone hydrochloride eliminated only [Ile(9)]PK20-evoked decline in tidal volume response. Blockade of NTS1 receptors with an intravenous dose of SR 142,948, lessened the remaining cardiorespiratory effects. This study depicts that [Ile(9)]PK20 acting through neurotensin NTS1 receptors augments the tidal component of the breathing pattern and activates respiratory timing response through the vagal pathway. Blood pressure effects occur outside vagal afferentation and might result from activation of the central and peripheral vascular NTS1 receptors. In summary the respiratory effects of the hybrid appeared not to be profound, but they were accompanied with unfavourable prolonged hypotension. Copyright © 2014 Elsevier B.V. All rights reserved.

Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

PubMed

Morimoto-Kobayashi, Yumie; Ohara, Kazuaki; Takahashi, Chika; Kitao, Sayoko; Wang, Guanying; Taniguchi, Yoshimasa; Katayama, Mikio; Nagai, Katsuya

2015-01-01

Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or

Reflex effects following selective stimulation of J receptors in the cat.

PubMed Central

Anand, A; Paintal, A S

1980-01-01

1. Experiments carried out on anaesthetized cats showed that increasing blood flow, through the lobes of a lung, by 133% (S.E. 33%) generated an average of 0.75 impulses/sec (S.E. 0.3) in ten almost silent J receptors. Equivalent activity was produced by injecting 12-18 micrograms phenyl diguanide/kg into the right atrium. Such activity caused marked reflex effects, i.e. apnoea, rapid shallow breathing and reduction in the knee jerk. 2. The reflex effects of J receptors were studied after blocking the activity from cardiac receptors by intrapericardial injections of xylocaine. This was necessary because left atrial injections of phenyl diguanide produced reflex respiratory effects and inhibition of the knee jerk. 3. Hypoxia, but not hypercapnia, attenuated the reflex effects of J receptors, apnoea being abolished if the Pa,O2 fell below 35 mmHg. This was a central effect as it occurred in spite of increased activity of J receptors following phenyl diguanide, and effects of hypoxia persisted after cutting both carotid nerves. 4. The only invariable reflex effect of J receptors was a reduction in the total number and the average frequency of phrenic impulses in each breath. The changes in inspiratory time (ti) and expiratory time (te) following apnoea were variable although most frequently both were reduced. In about half the observations the first effect before the apnoea was a reduction in ti, in the other half it was a reduction in te. It was concluded that an input from J receptors inhibits inspiratory and expiratory mechanisms directly. 5. In some cats apnoea and rapid shallow breathing produced by J receptors continued after interrupting their activity by vagotomy and this did not diminish the reduction in ti or te; in other cats it did. The reduction in te was at times quite independent of changes in ti, i.e. pulmonary stretch receptor activity. 6. It was concluded that J receptors must be stimulated during moderate exercise to levels that produce marked

Evidence for the gastric cytoprotective effect of centrally injected agmatine.

PubMed

Zádori, Zoltán S; Tóth, Viktória E; Fehér, Ágnes; Philipp, Kirsch; Németh, József; Gyires, Klára

2014-09-01

Agmatine (decarboxylated arginine) exerts cytoprotective action in several tissues, such as in the brain, heart or kidneys, but there is still controversy over the effects of agmatine on the gastric mucosa. The aim of the present study was to reveal the potential gastroprotective action of agmatine by using an acid-independent ulcer model to clarify which receptors and peripheral factors are involved in it. Gastric mucosal damage was induced by acidified ethanol. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. It was found that agmatine given intracerebroventricularly (i.c.v., 0.044-220 nmol/rat) significantly inhibited the development of ethanol-induced mucosal damage, while in the case of intraperitoneal injection (0.001-50mg/kg i.p.) it had only a minor effect. The central gastroprotective action of agmatine was completely antagonized by mixed alpha2-adrenoceptor and imidazoline I1 receptor antagonists (idazoxan, efaroxan), but only partially by yohimbine (selective alpha2-adrenoceptor antagonist) and AGN 192403 (selective I1 receptor ligand, putative antagonist). It was also inhibited by the non-selective opioid-receptor antagonist naloxone and the selective δ-opioid receptor antagonist naltrindole, but not by β-funaltrexamine and nor-Binaltorphimine (selective μ- and κ-opioid receptor antagonists, respectively). Furthermore, the effect of agmatine was antagonized by bilateral cervical vagotomy and by pretreatment with indomethacin and NG-nitro-l-arginine. Agmatine also reversed the ethanol-induced reduction of gastric mucosal CGRP and somatostatin content, but did not have any significant effect on gastric motor activity. These results indicate that agmatine given centrally induces gastric cytoprotection, which is mediated by central imidazoline I1 receptors, alpha2-adrenoceptors and δ-opioid receptors. Activation of

A prospective cohort study of postoperative complications in the management of perforated peptic ulcer.

PubMed

Sharma, Smita S; Mamtani, Manju R; Sharma, Mamta S; Kulkarni, Hemant

2006-06-16

With dwindling rates of postoperative mortality in perforated peptic ulcer that is attributable to H2-receptor blocker usage, there is a need to shift the focus towards the prevention of postoperative morbidity. Further, the simultaneous contribution of several putative clinical predictors to this postoperative morbidity is not fully appreciated. Our objective was to assess the predictors of the risk, rate and number of postoperative complications in surgically treated patients of perforated peptic ulcer. In a prospective cohort study of 96 subjects presenting as perforated peptic ulcer and treated using Graham's omentoplatsy patch or gastrojejunostomy (with total truncal vagotomy), we assessed the association of clinical predictors with three domains of postoperative complications: the risk of developing a complication, the rate of developing the first complication and the risk of developing higher number of complications. We used multiple regression methods - logistic regression, Cox proportional hazards regression and Poisson regression, respectively - to examine the association of the predictors with these three domains. We observed that the risk of developing a postoperative complication was significantly influenced by the presence of a concomitant medical illness [odds ratio (OR) = 8.9, p = 0.001], abdominal distension (3.8, 0.048) and a need of blood transfusion (OR = 8.2, p = 0.027). Using Poisson regression, it was observed that the risk for a higher number of complications was influenced by the same three factors [relative risk (RR) = 2.6, p = 0.015; RR = 4.6, p < 0.001; and RR = 2.4, p = 0.002; respectively]. However, the rate of development of complications was influenced by a history suggestive of shock [relative hazards (RH) = 3.4, p = 0.002] and A- blood group (RH = 4.7, p = 0.04). Abdominal distension, presence of a concomitant medical illness and a history suggestive of shock at the time of admission warrant a closer and alacritous postoperative

The role of the superior laryngeal nerve in esophageal reflexes

PubMed Central

Medda, B. K.; Jadcherla, S.; Shaker, R.

2012-01-01

The aim of this study was to determine the role of the superior laryngeal nerve (SLN) in the following esophageal reflexes: esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-lower esophageal sphincter (LES) relaxation reflex (ELIR), secondary peristalsis, pharyngeal swallowing, and belch. Cats (N = 43) were decerebrated and instrumented to record EMG of the cricopharyngeus, thyrohyoideus, geniohyoideus, and cricothyroideus; esophageal pressure; and motility of LES. Reflexes were activated by stimulation of the esophagus via slow balloon or rapid air distension at 1 to 16 cm distal to the UES. Slow balloon distension consistently activated EUCR and ELIR from all areas of the esophagus, but the distal esophagus was more sensitive than the proximal esophagus. Transection of SLN or proximal recurrent laryngeal nerves (RLN) blocked EUCR and ELIR generated from the cervical esophagus. Distal RLN transection blocked EUCR from the distal cervical esophagus. Slow distension of all areas of the esophagus except the most proximal few centimeters activated secondary peristalsis, and SLN transection had no effect on secondary peristalsis. Slow distension of all areas of the esophagus inconsistently activated pharyngeal swallows, and SLN transection blocked generation of pharyngeal swallows from all levels of the esophagus. Slow distension of the esophagus inconsistently activated belching, but rapid air distension consistently activated belching from all areas of the esophagus. SLN transection did not block initiation of belch but blocked one aspect of belch, i.e., inhibition of cricopharyngeus EMG. Vagotomy blocked all aspects of belch generated from all areas of esophagus and blocked all responses of all reflexes not blocked by SLN or RLN transection. In conclusion, the SLN mediates all aspects of the pharyngeal swallow, no portion of the secondary peristalsis, and the EUCR and ELIR generated from the proximal esophagus. Considering that SLN is not

A Respiratory Marker Derived From Left Vagus Nerve Signals Recorded With Implantable Cuff Electrodes.

PubMed

Sevcencu, Cristian; Nielsen, Thomas N; Kjaergaard, Benedict; Struijk, Johannes J

2018-04-01

Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings. The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms. The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (R 2 values between 0.85 and 0.99). The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems. © 2017 International Neuromodulation Society.

Changing patterns in the surgical treatment of perforated duodenal ulcer - single centre experience.

PubMed

Budzyński, Piotr; Pędziwiatr, Michał; Grzesiak-Kuik, Agata; Natkaniec, Michał; Major, Piotr; Matłok, Maciej; Stanek, Maciej; Wierdak, Mateusz; Migaczewski, Marcin; Pisarska, Magdalena; Budzyński, Andrzej

2015-09-01

Although the surgical treatment of patients with perforated duodenal ulcer is the method of choice, the introduction of effective pharmacotherapy has changed the surgical strategy. Nowadays less extensive procedures are chosen more frequently. The introduction of laparoscopic procedures had a significant impact on treatment results. To present our experience in the treatment of perforated duodenal ulcer in two periods, by comparing open radical anti-ulcer procedures with laparoscopic ulcer repair. The analysis covered patients operated on for perforated duodenal ulcer. Two groups of patients were compared. Group 1 included 245 patients operated on in the period 1980-1994 with a traditional method (pyloroplasty + vagotomy) before introduction of proton pump inhibitors (PPI). Group 2 included 106 patients treated in the period 2000-2014 with the laparoscopic technique supplemented with PPI therapy. Groups were compared in terms of patients' demographic structure, operative time, complication rate and mortality. The mean operative time in group 1 was shorter than in group 2 (p < 0.0001). Complications were noted in 57 (23.3%) patients in group 1 and 14 (13.5%) patients in group 2 (p = 0.0312). Reoperation was necessary in 13 (5.3%) cases in group 1 and in 5 cases in group 2 (p = 0.8179). The mortality rate in group 1 was significantly higher than in group 2 (10.2% vs. 2.8%, p = 0.0192). In group 1, median length of hospital stay was 9 days and differed significantly from group 2 (6 days, p < 0.0001). Within the last 30 years, significant changes in treatment of perforated peptic ulcer (PPU) have occurred, mainly related to abandoning routine radical anti-ulcer procedures and replacing the open technique with minimally invasive surgery. Thus it was possible to improve treatment results by reducing complication and mortality rates, and shortening the length of hospital stay. Although the laparoscopic operation is longer, it improves outcomes. In the authors' opinion, in

Duodenal bicarbonate secretion and mucosal protection. Neurohumoral influence and transport mechanisms.

PubMed

Säfsten, B

1993-01-01

Duodenal mucosal bicarbonate secretion (DMBS) plays an important role in the defence against acid discharged from the stomach. The secretion by duodenum immediately distal to the Brunner's glands area and devoid of pancreatic and biliary secretions, was investigated in vivo in anaesthetized Sprague-Dawley rats and in vitro in mucosae isolated from the American bullfrog. Transport mechanisms were studied in isolated rat duodenal enterocytes and identified by use of digitized microfluorometry and the fluoroprobe BCECF. Cyclic AMP production in enterocytes of villus vs. crypt origin was measured with radioimmunoassay. The benzodiazepines diazepam and Ro 15-1788 stimulated DMBS in the rat when administered intravenously or intracerebroventricularly; however, their stimulatory effect was abolished by bilateral proximal vagotomy, and they had no effect on the secretion by isolated bullfrog mucosa. It is concluded that these benzodiazepines stimulate secretion by acting upon the central nervous system and that their effects are vagally mediated. Dopamine, the catechol-O-methyl-transferase-inhibitor nitecapone, and the dopamine D1 agonist SKF-38393 all stimulated DMBS. The peripherally acting antagonist domperidone while having no influence on basal DMBS did prevent the influences of SKF-38393 and nitecapone. The alpha 1-antagonist prazosin had no such effects and the combined results suggest that DMBS is stimulated via peripheral dopamine D1 receptors. Intravenous, but not central nervous, administration of the muscarinic M1 receptor antagonists pirenzepine and telenzepine effectively stimulated DMBS; however their effectiveness was dependent on intact vagal nerves. Phentolamine, an unselective alpha-adrenergic antagonist, prevented the stimulation by pirenzepine and telenzepine and stimulation by carbachol was abolished by hexamethonium. It is concluded that peripheral nicotinergic and muscarinergic M1 receptors mediate stimulation of DMBS, in part by acting upon

A national review of the frequency of minimally invasive surgery among general surgery residents: assessment of ACGME case logs during 2 decades of general surgery resident training.

PubMed

Richards, Morgan K; McAteer, Jarod P; Drake, F Thurston; Goldin, Adam B; Khandelwal, Saurabh; Gow, Kenneth W

2015-02-01

Minimally invasive surgery (MIS) has created a shift in how many surgical diseases are treated. Examining the effect on resident operative experience provides valuable insight into trends that may be useful for restructuring the requirements of resident training. To evaluate changes in general surgery resident operative experience regarding MIS. Retrospective review of the frequency of MIS relative to open operations among general surgery residents using the Accreditation Council for Graduate Medical Education case logs for academic years 1993-1994 through 2011-2012. General surgery residency training among accredited programs in the United States. We analyzed the difference in the mean number of MIS techniques and corresponding open procedures across training periods using 2-tailed t tests with statistical significance set at P < .05. Of 6,467,708 operations with the option of MIS, 2,393,030 (37.0%) were performed with the MIS approach. Of all MIS operations performed, the 5 most common were cholecystectomy (48.5%), appendectomy (16.2%), groin hernia repair (10.0%), abdominal exploration (nontrauma) (4.4%), and antireflux procedures (3.6%). During the study period, there was a transition from a predominantly open to MIS approach for appendectomy, antireflux procedures, thoracic wedge resection, and partial gastric resection. Cholecystectomy is the only procedure for which MIS was more common than the open technique throughout the study period (P < .001). The open approach is more common for all other procedures, including splenectomy (0.7% MIS), common bile duct exploration (24.9% MIS), gastrostomy (25.9% MIS), abdominal exploration (33.1% MIS), hernia (20.3% MIS), lung resection (22.3% MIS), partial or total colectomy (39.1%), enterolysis (19.0% MIS), ileostomy (9.0% MIS), enterectomy (5.2% MIS), vagotomy (1.8% MIS), and pediatric antireflux procedures (35.9% MIS); P < .001. Minimally invasive surgery has an increasingly prominent role in contemporary

Peripheral α2-β1 adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats

PubMed Central

Yakabi, Koji; Harada, Yumi; Takayama, Kiyoshige; Ro, Shoki; Ochiai, Mitsuko; lizuka, Seiichi; Hattori, Tomohisa; Wang, Lixin; Taché, Yvette

2018-01-01

Summary The autonomic nervous system (ANS) conveys neuronal input from the brain to the stomach. We investigated mechanisms through which urocortin 1 (UCN1) injected intracerebroventricularly (ICV, 300 pmol/rat) inhibits circulating ghrelin in rats. This was achieved by assessing (1) the induction of c-fos gene expression as a marker of neuronal activation in specific hypothalamic and caudal brainstem regulating ANS; (2) the influence of vagotomy and pharmacological blockade of central and peripheral α- and β-adrenergic receptor (AR) on ICV UCN1 -induced reduction of plasma ghrelin levels (determined by ELISA); and (3) the relevance of this pathway in the feeding response to a fast in rats. UCN1 increased c-fos mRNA expression in key brain sites influencing sympathetic activity namely the hypothalamic paraventricular and ventromedial nuclei, locus coeruleus, nucleus of the solitary tract, and rostral ventrolateral medulla, by 16-, 29-, 6-, 37-, and 13-fold, respectively. In contrast, the dorsal motor nucleus of the vagus had little c-fos mRNA expression and ICV UCN1 induced a similar reduction in acylated ghrelin in the sham-operated (31%) and vagotomized (41%) rats. An intraperitoneal (IP) injection of either a non-selective α- or selective α2-AR antagonist reduced, while a selective α2-AR agonist enhanced ICV UCN1-induced suppression of plasma acylated ghrelin levels. In addition, IP injection of a non-selective β- or selective β1-AR agonist blocked, and selective β1-AR antagonist augmented, the ghrelin response to ICV UCN1. The IP injections of a selective α1- or non-selective β or β2-AR antagonists, or any of the pretreatments given ICV had no effect. ICV UCN1 reduced the 2-h food intake in response to a fast by 80%, and this effect was partially prevented by a selective α2-AR antagonist. These data suggest that ICV UCN1 reduces plasma ghrelin mainly through the brain sympathetic component of the ANS and peripheral AR specifically α2-AR activation

Cardiovascular effects of the essential oil of Aniba canelilla bark in normotensive rats.

PubMed

Lahlou, Saad; Magalhães, Pedro Jorge Caldas; de Siqueira, Rodrigo José Bezerra; Figueiredo, André Fernandes; Interaminense, Leylliane Fátima Leal; Maia, José Guilherme Soares; Sousa, Pergentino José da Cunha

2005-10-01

Cardiovascular effects of intravenous (i.v.) treatment with the essential oil of the bark of Aniba canelilla (EOAC) were investigated in normotensive rats. In both pentobarbital-anesthetized and conscious rats, i.v. bolus injections of EOAC (1 to 20 mg/kg) elicited similar and dose-dependent hypotension and bradycardia. Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardia without affecting the hypotension. In conscious rats, pretreatment with hexamethonium (30 mg/kg, i.v.) significantly reduced the EOAC-induced bradycardia without affecting the hypotension. The opposite effect was observed after i.v. pretreatment with the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl esther (L-NAME, 20 mg/kg). However, both EOAC-induced hypotension and bradycardia were significantly reduced by pretreatment with methylatropine (1 mg/kg, i.v.). In rat endothelium-containing aorta preparations, EOAC (1-600 microg/mL) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction [IC50 (geometric mean+/-95% confidence interval)=64.5 (45.6-91.2) microg/mL)], an effect that was significantly reduced by the addition of atropine (10 microM) in the perfusion medium [IC50=109.5 (72.5-165.4) microg/mL)]. Furthermore, the vasorelaxant effects of the EOAC were also but significantly reduced [IC50=139.1 (105.2-183.9) microg/mL)] by removal of the vascular endothelium. Furthermore, the CaCl2-induced contractions in calcium-free medium were reduced and even fully abolished by EOAC (100 and 600 microg/mL), respectively. However, EOAC (600 microg/mL) was without significant effect on caffeine-induced contractions in calcium-free medium. These data show that i.v. treatment of rats with EOAC induces dose-dependent hypotension and bradycardia, which occurred independently. The bradycardia appears mainly dependent upon the presence of an operational and functional parasympathetic drive to the heart. However, the hypotension is

Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell.

PubMed

Mulherin, Andrew J; Oh, Amy H; Kim, Helena; Grieco, Anthony; Lauffer, Lina M; Brubaker, Patricia L

2011-12-01

Glucagon-like peptide-1(7-36NH2) (GLP-1) is secreted by the intestinal L cell in response to both nutrient and neural stimulation, resulting in enhanced glucose-dependent insulin secretion. GLP-1 is therefore an attractive therapeutic for the treatment of type 2 diabetes. The antidiabetic drug, metformin, is known to increase circulating GLP-1 levels, although its mechanism of action is unknown. Direct effects of metformin (5-2000 μm) or another AMP kinase activator, aminoimidazole carboxamide ribonucleotide (100-1000 μm) on GLP-1 secretion were assessed in murine human NCI-H716, and rat FRIC L cells. Neither agent stimulated GLP-1 secretion in any model, despite increasing AMP kinase phosphorylation (P < 0.05-0.01). Treatment of rats with metformin (300 mg/kg, per os) or aminoimidazole carboxamide ribonucleotide (250 mg/kg, sc) increased plasma total GLP-1 over 2 h, reaching 37 ± 9 and 29 ± 9 pg/ml (P < 0.001), respectively, compared with basal (7 ± 1 pg/ml). Plasma activity of the GLP-1-degrading enzyme, dipeptidylpeptidase-IV, was not affected by metformin treatment. Pretreatment with the nonspecific muscarinic antagonist, atropine (1 mg/kg, iv), decreased metformin-induced GLP-1 secretion by 55 ± 11% (P < 0.05). Pretreatment with the muscarinic (M) 3 receptor antagonist, 1-1-dimethyl-4-diphenylacetoxypiperidinium iodide (500 μg/kg, iv), also decreased the GLP-1 area under curve, by 48 ± 8% (P < 0.05), whereas the antagonists pirenzepine (M1) and gallamine (M2) had no effect. Furthermore, chronic bilateral subdiaphragmatic vagotomy decreased basal secretion compared with sham-operated animals (7 ± 1 vs. 13 ± 1 pg/ml, P < 0.001) but did not alter the GLP-1 response to metformin. In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 μg/kg, sc), reduced the GLP-1 response to metformin, by 55 ± 6% (P < 0.01) at 30 min. These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the

Lester R. Dragstedt 1893-1975. Chronic ulcerative colitis. A summary of evidence implicating Bacterium necrophorum as an etiologic agent.

PubMed

1988-08-01

Lester Dragstedt was born in Anaconda, Montana, the son of Swedish immigrant parents. His entire college and professional education took place at the University of Chicago, where he received a B.S. degree in 1915, a master's degree in physiology in 1916, a Ph.D. in physiology in 1920, and the M.D. degree (from Rush) in 1921. His first academic appointment was as a physiologist at the State University of Iowa. In 1925 Dragstedt was recruited by Dallas B. Phemister to help design the new University Hospital research facilities on the campus of the University of Chicago. Following completion of this responsibility Phemister appointed Dragstedt as Associate Professor of Surgery, stating, "I can teach surgery to a physiologist; I am interested in teaching physiology to surgeons." In 1947 Dragstedt succeeded Phemister as chairman, a post he occupied until his retirement in 1959. Dragstedt was regarded as a skilled clinician as well as a dexterous and artistic surgeon. But he was particularly recognized for his contributions as physiologist-surgeon in the treatment of diseases of the pancreas, parathyroids, and especially diseases of the stomach. In 1943, he performed a transthoracic vagotomy on a patient with a duodenal ulcer who refused to accept the standard operation, subtotal gastrectomy. A lesser known but classical work of Dragstedt and his coworkers is reproduced here for this series. Dragstedt was the originator of the skin-grafted ileostomy in the treatment of ulcerative colitis. The author describes a complete "take" of the split-thickness graft in four patients, although he observed that the "resulting ileostomy looked somewhat like a penis." One can only surmise about the psychologic disability that would be produced. The stoma could, however, be fitted with an appliance that would minimize the risk of abdominal wall digestion. When reading the article and understanding the experimental studies proposing the possible causative organism of ulcerative colitis

Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach

PubMed Central

Adami, Maristella; Frati, Paolo; Bertini, Simone; Kulkarni-Narla, Anjali; Brown, David R; Caro, Giuseppe de; Coruzzi, Gabriella; Soldani, Giulio

2002-01-01

The role of cannabinoid (CB) receptors in the regulation of gastric acid secretion was investigated in the rat by means of functional experiments and by immunohistochemistry. In anaesthetized rats with lumen-perfused stomach, the non selective CB-receptor agonist WIN 55,212-2 (0.30 – 4.00 μmol kg−1, i.v.) and the selective CB1-receptor agonist HU-210 (0.03 – 1.50 μmol kg−1, i.v.), dose-dependently decreased the acid secretion induced by both pentagastrin (30 nmol kg−1 h−1) and 2-deoxy-D-glucose (1.25 mmol kg−1, i.v.). By contrast, neither WIN 55,212-2 (1 – 4 μmol kg−1, i.v.) nor HU-210 (0.03 – 1.50 μmol kg−1, i.v.) did modify histamine-induced acid secretion (20 μmol kg−1 h−1). The selective CB2-receptor agonist JWH-015 (3 – 10 μmol kg−1, i.v.) was ineffective. The gastric antisecretory effects of WIN 55,212-2 and HU-210 on pentagastrin-induced acid secretion were prevented by the selective CB1-receptor antagonist SR141716A (0.65 μmol kg−1, i.v.) and unaffected by the selective CB2-receptor antagonist SR144528 (0.65 – 2 μmol kg−1, i.v.). Bilateral cervical vagotomy and ganglionic blockade with hexamethonium (10 mg kg−1, i.v., followed by continuous infusion of 10 mg kg−1 h−1) significantly reduced, but not abolished, the maximal inhibitory effect of HU-210 (0.3 μmol kg−1, i.v.) on pentagastrin-induced acid secretion; by contrast, pretreatment with atropine (1 mg kg−1, i.v.) did not modify the antisecretory effect of HU-210. Immunoreactivity to the CB1 receptor was co-localized with that of the cholinergic marker choline acetyltransferase in neural elements innervating smooth muscle, mucosa and submucosal blood vessels of rat stomach fundus, corpus and antrum. In contrast, CB2 receptor-like immunoreactivity was not observed. These results indicate that gastric antisecretory effects of cannabinoids in the rat are mediated by

Total gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of hepatic vagus branch and lower esophageal sphincter for T2 gastric cancer without lymph node metastasis.

PubMed

Tomita, Ryouichi; Tanjoh, Katsuhisa; Fujisaki, Shigeru

2004-01-01

In order to improve postgastrectomy disorders of patients with T2 (MP or SS) gastric cancer without lymph node metastasis, which mainly locates in the middle third of stomach, we have performed a total gastrectomy preserving both hepatic vagus branches and the lower esophageal sphincter as a function-preserving surgical procedure. In the present study, the application criteria and points of the technique are outlined, and postoperative quality of life is clinically investigated. Twenty-four subjects who underwent this surgical operation (group A; 16 men and 8 women subjects aged 46 to 73 years, mean age 62.2 years) were interviewed regarding appetite, weight loss, reflux esophagitis, dumping syndrome, and microgastria. Cholelithiasis following total gastrectomy was also checked by abdominal ultrasonography. Group A was compared with 26 cases of conventional total gastrectomy with D2 lymphadenectomy, excision of lower esophageal sphincter, total vagotomy, and single jejunal interposition (B group; 19 men and 7 women subjects aged 42 to 75 years, mean age 64.8 years). Application criteria of the technique: Included were cases with T2 cancer of N0 mainly localizing at the middle-third of the stomach which was 4 cm or further in distance from the oral-side margin of the cancer to the esophagogastric mucosa junction. Points of the technique: In lymphadenectomy, hepatic branches of the vagal nerve only preserved. To preserve lower esophageal sphincter, the abdominal esophagus was severed at the level of His angle to the longitudinal axis of the esophagus. Substitute stomach was created as a 15-cm jejunal pouch with a 5-cm-long jejunal conduit for isoperistaltic movement. In group A the food ingestion rate was significantly greater than that of group B (P<0.001) at 6 months and 2.0 years after operation, with no reflux esophagitis or dumping syndrome being noticed at 2.0 years after operation. In group B, loss of appetite 2.0 years after operation was significantly higher

Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat.

PubMed

Brzozowski, T; Konturek, P C; Konturek, S J; Kwiecién, S; Pajdo, R; Brzozowska, I; Hahn, E G

1998-01-01

GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA. We conclude that endogenous CCK released by oleate or diversion of pancreatic secretion exerts a potent gastroprotective action on the stomach involving predominantly CCK-A receptors and depending on vagal activity, and hyperemia mediated by NO and sensory nerves but unrelated to acid secretory effects and endogenous PG.

Experience with acute perforated duodenal ulcer in a West African population.

PubMed

Nuhu, A; Kassama, Y

2008-01-01

between presentation and surgery was 9 hours (range 6-11 hours). The mean size of perforation was 10.5 mm (range 5-15 mm). Definitive peptic ulcer surgery was done in 12 (29.3%) patients. 8 had truncal vagotomy and pyloroplasty. The major complications included wound infection in 14 (34.1%), postoperative fever in 16 (39.0%) and prolonged ileus in 15 (36.6%) There were 7 deaths, mortality rate of 17.1% and the causes of death included severe electrolyte imbalance in 1 and gram negative septicaemia and shock in 6. The average duration of hospital stay was 10 days (range 8-36). Perforated duodenal ulcer is a major complication of chronic peptic ulcer disease. Simple omental patch by open method and helicobacter pylori eradication therapy is sufficient to prevent reperforation.

Emergency gastric ulcer complications in elderly. Factors affecting the morbidity and mortality in relation to therapeutic approaches.

PubMed

Di Carlo, I; Toro, A; Sparatore, F; Primo, S; Barbagallo, F; Di Blasi, M

2006-08-01

(H2-receptor antagonist or proton pump inhibitors and in 7 patients [24.1%] antihaemorrhage drugs), and clinical observation, with a endoscopic control 3-4 days after from the first endoscopy. One of the 2 patients endoscopically treated developed a ulcer perforation after 11 days, and the other one rebled, without possibility of any kind of treatment due to his instable condition of health. Three patients (10.7%) died during their hospital stay not for causes strictly due to the gastric haemorrhage. Our results suggest that the early diagnoses and early treatment are 2 basic factor on the prognosis of elderly patients with perforated gastric ulcer. The choice between simple closure, with or without vagotomy, or gastrectomy depends from preoperative and operative health conditions of the patient. In patients with ulcer larger than 2 cm, Graham's technique can be performed safely if the preoperative and intraoperative conditions are favourable. Elderly patients with gastric ulcer bleeding show an high risk of morbidity and mortality, related to the risk factors like non steroid anti-inflammatory drugs (NSAIDs) intake or smoke. Repeated endoscopy and antiulcer drugs can manage the high stage patients of Forrest's classification with a low rate of morbidity and mortality. According to literature surgical treatment should be reserved after the second failure of endoscopic treatment.

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex.

PubMed

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-12-15

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of L-glutamate at the same sites, and both the effects of L-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

PubMed Central

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-01-01

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)−1) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to −0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of l-glutamate at the same sites, and both the effects of l-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure

Gastric Electrical Stimulation

PubMed Central

2006-01-01

Executive Summary Objective The objective of this analysis was to assess the effectiveness, safety and cost-effectiveness of gastric electrical stimulation (GES) for the treatment of chronic, symptomatic refractory gastroparesis and morbid obesity. Background Gastroparesis - Epidemiology Gastroparesis (GP) broadly refers to impaired gastric emptying in the absence of obstruction. Clinically, this can range from the incidental detection of delayed gastric emptying in an asymptomatic person to patients with severe nausea, vomiting and malnutrition. Symptoms of GP are nonspecific and may mimic structural disorders such as ulcer disease, partial gastric or small bowel obstruction, gastric cancer, and pancreaticobiliary disorders. Gastroparesis may occur in association with diabetes, gastric surgery (consequence of peptic ulcer surgery and vagotomy) or for unknown reasons (idiopathic gastroparesis). Symptoms include early satiety, nausea, vomiting, abdominal pain and weight loss. The majority of patients with GP are women. The relationship between upper gastrointestinal symptoms and the rate of gastric emptying is considered to be weak. Some patients with markedly delayed gastric emptying are asymptomatic and sometimes, severe symptoms may remit spontaneously. Idiopathic GP may represent the most common form of GP. In one tertiary referral retrospective series, the etiologies in 146 GP patients were 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson’s disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction and 6% miscellaneous causes. The true prevalence of digestive symptoms in patients with diabetes and the relationship of these symptoms to delayed gastric emptying are unknown. Delayed gastric emptying is present in 27% to 58% of patients with type 1 diabetes and 30% with type 2 diabetes. However, highly variable rates of gastric emptying have been reported in type 1 and 2 diabetes, suggesting that development of GP in