The surgical management of complicated peptic ulcer disease: An EAST video presentation.

BACKGROUND: Peptic ulcer disease (PUD), once primary a surgical problem, is now medically managed in the majority of patients. The surgical treatment of PUD is now strictly reserved for life-threatening complications. Free perforation, refractory bleeding and gastric outlet obstruction, although rare in the age of medical management of PUD, are several of the indications for surgical intervention. The acute care surgeon caring for patients with PUD should be facile in techniques required for bleeding control, bypass of peptic strictures, and vagotomy with resection and reconstruction. This video procedures and techniques article demonstrates these infrequently encountered, but critical operations. CONTENT VIDEO DESCRIPTION: A combination of anatomic representations and videos of step-by-step instructions on perfused cadavers will demonstrate the key steps in the following critical operations. Graham patch repair of perforated peptic ulcer is demonstrated in both open and laparoscopic fashion. The choice to perform open versus laparoscopic repair is based on individual surgeon comfort. Oversewing of a bleeding duodenal ulcer via duodenotomy and ligation of the gastroduodenal artery is infrequent in the age of advanced endoscopy and interventional radiology techniques, yet this once familiar procedure can be lifesaving. Repair of giant duodenal or gastric ulcers can present a challenging operative dilemma on how to best repair or exclude the defect. Vagotomy and antrectomy, perhaps the least common of all the aforementioned surgical interventions, may require more complex reconstruction than other techniques making it challenging for inexperienced surgeons. A brief demonstration on reconstruction options will be shown, and it includes Roux-en-Y gastrojejunostomy. CONCLUSION: Surgical management of PUD is reserved today for life-threatening complications for which the acute care surgeon must be prepared. This presentation provides demonstration of key surgical principles in management of bleeding and free perforation, as well as gastric resection, vagotomy and reconstruction. LEVEL OF EVIDENCE: Video procedure and technique, not applicable.

The role of the vagus nerve on dexmedetomidine promoting survival and lung protection in a sepsis model in rats.

BACKGROUND: Sepsis often results in acute lung injury (ALI). Dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in lipopolysaccharide (LPS)-induced ALI rats. METHODS: The bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed as sham surgery. After LPS administration, Dex antagonist yohimbine (YOH) and/or Dex was injected intraperitoneally to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores. The plasma concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), catecholamine and acetylcholine were measured with enzyme-linked immunosorbent assay. RESULTS: The median survival time of LPS-induced ALI rats was prolonged by Dex (22 h, 95% CI, [24.46, 92.20]) vs. 14 h, 95% CI, [14.60, 89.57] of the LPS control group, P < 0.05), and the ALI score was reduced by Dex (6.5, 95% CI, [5.23, 8.10] vs. 11.5, 95% CI, [10.23, 13.10] in the LPS group, P < 0.01). However, these protective effects were significantly decreased by either YOH administration or vagotomy. Dex decreased LPS-induced IL-1ß, TNF-α, and catecholamine but increased acetylcholine in blood serum; these effects of Dex was partially abolished by vagotomy. CONCLUSIONS: Our data suggested that Dex increased vagal nerve tone that partially contributed to its anti-inflammatory and lung-protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and α2-adrenoceptor activation, respectively.

Vagotomy and Splenectomy Reduce Insulin Secretion and Interleukin-1ß.

OBJECTIVES: This study aimed to evaluate the effect of vagotomy, when associated with splenectomy, on adiposity and glucose homeostasis in Wistar rats. METHODS: Rats were divided into 4 groups: vagotomized (VAG), splenectomized (SPL), VAG + SPL, and SHAM. Glucose tolerance tests were performed, and physical and biochemical parameters evaluated. Glucose-induced insulin secretion and protein expression (Glut2/glucokinase) were measured in isolated pancreatic islets. Pancreases were submitted to histological and immunohistochemical analyses, and vagus nerve neural activity was recorded. RESULTS: The vagotomized group presented with reduced body weight, growth, and adiposity; high food intake; reduced plasma glucose and triglyceride levels; and insulin resistance. The association of SPL with the VAG surgery attenuated, or abolished, the effects of VAG and reduced glucose-induced insulin secretion and interleukin-1ß area in ß cells, in addition to lowering vagal activity. CONCLUSIONS: The absence of the spleen attenuated or blocked the effects of VAG on adiposity, triglycerides and glucose homeostasis, suggesting a synergistic effect of both on metabolism. The vagus nerve and spleen modulate the presence of interleukin-1ß in ß cells, possibly because of the reduction of glucose-induced insulin secretion, indicating a bidirectional flow between autonomous neural firing and the spleen, with repercussions for the endocrine pancreas.

Unilateral vagotomy alters astrocyte and microglial morphology in the nucleus tractus solitarii of the rat.

The nucleus tractus solitarii (nTS) is the initial site of integration of sensory information from the cardiorespiratory system and contributes to reflex responses to hypoxia. Afferent fibers of the bilateral vagus nerves carry input from the heart, lungs, and other organs to the nTS where it is processed and modulated. Vagal afferents and nTS neurons are integrally associated with astrocytes and microglia that contribute to neuronal activity and influence cardiorespiratory control. We hypothesized that vagotomy would alter glial morphology and cardiorespiratory responses to hypoxia. Unilateral vagotomy (or sham surgery) was performed in rats. Prior to and seven days after surgery, baseline and hypoxic cardiorespiratory responses were monitored in conscious and anesthetized animals. The brainstem was sectioned and caudal, mid-area postrema (mid-AP), and rostral sections of the nTS were prepared for immunohistochemistry. Vagotomy increased immunoreactivity (-IR) of astrocytic glial fibrillary acidic protein (GFAP), specifically at mid-AP in the nTS. Similar results were found in the dorsal motor nucleus of the vagus (DMX). Vagotomy did not alter nTS astrocyte number, yet increased astrocyte branching and altered morphology. In addition, vagotomy both increased nTS microglia number and produced morphologic changes indicative of activation. Cardiorespiratory baseline parameters and hypoxic responses remained largely unchanged, but vagotomized animals displayed fewer augmented breaths (sighs) in response to hypoxia. Altogether, vagotomy alters nTS glial morphology, indicative of functional changes in astrocytes and microglia that may affect cardiorespiratory function in health and disease.

Role of the parasympathetic nervous system in cancer initiation and progression

The nervous system plays an important role in cancer initiation and progression. Accumulated evidences clearly show that the sympathetic nervous system exerts stimulatory effects on carcinogenesis and cancer growth. However, the role of the parasympathetic nervous system in cancer has been much less elucidated. Whereas retrospective studies in vagotomized patients and experiments employing vagotomized animals indicate the parasympathetic nervous system has an inhibitory effect on cancer, clinical studies in patients with prostate cancer indicate it has stimulatory effects. Therefore, the aim of this paper is a critical evaluation of the available data related to the role of the parasympathetic nervous system in cancer (AU)

Role of the parasympathetic nervous system in cancer initiation and progression.

The nervous system plays an important role in cancer initiation and progression. Accumulated evidences clearly show that the sympathetic nervous system exerts stimulatory effects on carcinogenesis and cancer growth. However, the role of the parasympathetic nervous system in cancer has been much less elucidated. Whereas retrospective studies in vagotomized patients and experiments employing vagotomized animals indicate the parasympathetic nervous system has an inhibitory effect on cancer, clinical studies in patients with prostate cancer indicate it has stimulatory effects. Therefore, the aim of this paper is a critical evaluation of the available data related to the role of the parasympathetic nervous system in cancer.

Respiratory Sinus Arrhythmia Attenuation via Targeted Lung Denervation in Sheep and Humans.

BACKGROUND: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung. Parasympathetic input to the heart originating from the lungs contributes to respiratory sinus arrhythmia (RSA) and disruption of pulmonary nerves via TLD may impact RSA. OBJECTIVE: The aim of this study was to assess the potential of TLD to affect RSA in sheep and humans. METHODS: TLD was performed in 5 sheep and 9 humans using a novel lung denervation system (Nu-vaira Inc., Minneapolis, MN, USA) with an electrocardiogram collected before and after the procedure. Frequency domain analysis of heart rate variability was performed in 5 sheep and 6 humans with presence of RSA approximated as high-frequency power (HF power). RESULTS: HF power decreased in 3 of 5 sheep with 1 animal reaching less than 7% of its baseline HF power 30 days after TLD. The average treatment location was more distal in the remaining 2 animals, which did not exhibit RSA attenuation, suggesting diminished denervation. HF power decreased in 5 of 6 humans, with 3 subjects reaching less than 50% of their baseline HF power 90 days after TLD. CONCLUSIONS: TLD appeared to attenuate RSA in both sheep and human cohorts of this sub-study. Further confirmation in humans is necessary to allow for RSA attenuation to be used as a marker of successful lung denervation via TLD.

Capsaicin-induced visceral deafferentation does not attenuate flavor conditioning by intragastric fat infusions in mice.

The postoral actions of sugar and fat can rapidly stimulate the intake of and preference for flavors associated with these nutrients via a process known as appetition. Prior findings revealed that postoral glucose appetition is not attenuated following capsaicin-induced visceral deafferentation. The present experiment determined if capsaicin treatment altered fat appetition in C57BL/6 mice. Following capsaicin (Cap) or control (Con) treatment, mice were fitted with chronic intragastric (IG) catheters. They were then given 1-h sessions with a flavored saccharin solution (CS-) paired with IG water infusion or a different flavor (CS+) paired with IG 6.4% fat infusion. IG fat stimulated CS+ intakes in both Cap and Con mice, and the groups displayed similar preferences for CS+ over CS- in two-choice tests. These results confirm prior reports of normal fat conditioning in rats exposed to capsaicin or vagal deafferentation surgery. In contrast, other recent findings indicate that total or selective vagotomy alters the preference of mice for dilute vs. concentrated fat sources.

Interplay of spinal and vagal pathways on esophageal acid-related anterior cingulate cortex functional networks in rats.

Esophageal acid sensory signals are transmitted by both vagal and spinal pathways to the cerebral cortex. The influence and interplay of these pathways on esophageal acid-related functional connectivity has been elusive. Our aim was to evaluate the esophageal acid exposure-related effect on the anterior cingulate cortex (ACC) functional connectivity networks using functional MRI-guided functional connectivity MRI (fcMRI) analysis. We studied six Sprague-Dawley rats for fcMRI experiments under dexmedetomidine hydrochloride anesthesia. Each rat was scanned for 6 min before and after esophageal hydrochloric acid infusion (0.1 N, 0.2 ml/min). The protocol was repeated before and after bilateral cervical vagotomy on the same rat. Seed-based fcMRI analysis was used to examine ACC networks and acid-induced network alterations. Three-factor repeated-measures ANOVA analysis among all four subgroups revealed that the interaction of acid infusion and bilateral vagotomy was mainly detected in the hypothalamus, insula, left secondary somatosensory cortex, left parietal cortex, and right thalamus in the left ACC network. In the right ACC network, this interaction effect was detected in the caudate putamen, insula, motor, primary somatosensory cortex, secondary somatosensory cortex, and thalamic regions. These regions in the ACC networks showed decreased intranetwork connectivity due to acid infusion. However, after bilateral vagotomy, intranetwork connectivity strength inversed and became stronger following postvagotomy acid infusion. Signals transmitted through both the vagal nerve and spinal nerves play a role in esophageal acid-related functional connectivity of the ACC. The vagal signals appear to dampen the acid sensation-related functional connectivity of the ACC networks. NEW & NOTEWORTHY These studies show that esophageal acid-induced brain functional connectivity changes are vagally mediated and suggest that signals transmitted through both the vagal nerve and spinal nerves play a role in esophageal acid-related functional connectivity of the anterior cingulate cortex. This paper focuses on the development of a novel rat functional MRI model fostering improved understanding of acid-related esophageal disorders.

Pain-free survival after vagoglossopharyngeal complex sectioning with or without microvascular decompression in glossopharyngeal neuralgia.

OBJECTIVE: Glossopharyngeal neuralgia (GN) is a rare pain condition in which patients experience paroxysmal, lancinating throat pain. Multiple surgical approaches have been used to treat this condition, including microvascular decompression (MVD), and sectioning of cranial nerve (CN) IX and the upper rootlets of CN X, or a combination of the two. The aim of this study was to examine the long-term quality of life and pain-free survival after MVD and sectioning of the CN X/IX complex. METHODS: A combined retrospective chart review and a quality-of-life telephone survey were performed to collect demographic and long-term outcome data. Quality of life was assessed by means of a questionnaire based on a combination of the Barrow Neurological Institute pain intensity scoring criteria and the Brief Pain Inventory-Facial. Kaplan-Meier analysis was performed to determine pain-free survival. RESULTS: Of 18 patients with GN, 17 underwent sectioning of the CN IX/X complex alone or sectioning and MVD depending on the presence of a compressing vessel. Eleven of 17 patients had compression of CN IX/X by the posterior inferior cerebellar artery, 1 had compression by a vertebral artery, and 5 had no compression. One patient (6%) experienced no immediate pain relief. Fifteen (88%) of 17 patients were pain free at the last follow-up (mean 9.33 years, range 5.16-13 years). One patient (6%) experienced throat pain relapse at 3 months. The median pain-free survival was 7.5 years ± 10.6 months. Nine of 18 patients were contacted by telephone. Of the 17 patients who underwent sectioning of the CN IX/X complex, 13 (77%) patients had short-term complaints: dysphagia (n = 4), hoarseness (n = 4), ipsilateral hearing loss (n = 4), ipsilateral taste loss (n = 2), and dizziness (n = 2) at 2 weeks. Nine patients had persistent side effects at latest follow-up. Eight of 9 telephone respondents reported that they would have the surgery over again. CONCLUSIONS: Sectioning of the CN IX/X complex with or without MVD of the glossopharyngeal nerve is a safe and effective surgical therapy for GN with initial pain freedom in 94% of patients and an excellent long-term pain relief (mean 7.5 years).

Physiologic and histopathologic effects of targeted lung denervation in an animal model.

Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures. NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects.

Vago-Splenic Axis in Signal Transduction of Remote Ischemic Preconditioning in Pigs and Rats.

RATIONALE: The signal transduction of remote ischemic conditioning is still largely unknown. OBJECTIVE: Characterization of neurohumoral signal transfer and vago-splenic axis in remote ischemic preconditioning (RIPC). METHODS AND RESULTS: Anesthetized pigs were subjected to 60 minutes of coronary occlusion and 180 minutes of reperfusion (placebo+ischemia/reperfusion [PLA+I/R]). RIPC was induced by 4×5/5 minutes of hindlimb I/R 90 minutes before coronary occlusion (RIPC+I/R). Arterial blood samples were taken after placebo or RIPC before I/R. In subgroups of pigs, bilateral cervical vagotomy, splenectomy, or splenic denervation were performed before PLA+I/R or RIPC+I/R, respectively. In pigs with RIPC+I/R, infarct size (percentage of area at risk) was less than in those with PLA+I/R (23±12% versus 45±8%); splenectomy or splenic denervation abrogated (splenectomy+RIPC+I/R: 38±15%; splenic denervation+RIPC+I/R: 43±5%), and vagotomy attenuated (vagotomy+RIPC+I/R: 36±11%) RIPC protection. RIPC increased phosphorylation of STAT3 (signal transducer and activator of transcription 3) in left ventricular biopsies taken at early reperfusion. Splenectomy or splenic denervation, but not vagotomy, abolished this increased phosphorylation. In rats with vagotomy, splenectomy, or splenic denervation, RIPC (3×5/5 minutes of hindlimb occlusion/reperfusion) or placebo was performed, respectively. Hearts were isolated, saline perfused, and subjected to 30/120-minute global I/R. With RIPC, infarct size (percentage of ventricular mass) was less (20±7%) than with placebo (37±6%), and vagotomy, splenectomy, or splenic denervation abrogated RIPC protection (38±12%, 36±9%, and 36±7%), respectively. Rat spleens were isolated, saline perfused, and splenic effluate (SEff) was sampled after infusion with carbachol (SEffcarbachol) or saline (SEffsaline). Pig plasma or SEff was infused into isolated perfused rat hearts subjected to global I/R. Infarct size was less with infusion of RIPC+I/Rplasma+ (24±6%) than with PLA+I/Rplasma (40±8%), vagotomy+PLA+I/Rplasma (39±11%), splenectomy+PLA+I/Rplasma (35±8%), vagotomy+RIPC+I/Rplasma (40±9%), splenectomy+RIPC+I/Rplasma (33±9%), or splenic denervation+RIPC+I/Rplasma (39±8%), respectively. With infusion of SEffcarbachol, infarct size was less than with infusion of SEffsaline (24 [19-27]% versus 35 [32-38]%). CONCLUSIONS: Activation of a vago-splenic axis is causally involved in RIPC cardioprotection.

Short-chain fatty acids suppress food intake by activating vagal afferent neurons.

Fermentable carbohydrates including dietary fibers and resistant starch produce short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, through microbial fermentation in the intestine of rodents and humans. Consumption of fermentable carbohydrate and SCFAs suppress food intake, an effect involving the brain. However, their signaling pathway to the brain remains unclear. Vagal afferents serve to link intestinal information to the brain. In the present study, we explored possible role of vagal afferents in the anorexigenic effect of SCFAs. Intraperitoneal (ip) injection of three SCFA molecules (6 mmol/kg) suppressed food intake in fasted mice with the rank order of butyrate > propionate > acetate. The suppressions of feeding by butyrate, propionate and acetate were attenuated by vagotomy of hepatic branch and blunted by systemic treatment with capsaicin that denervates capsaicin-sensitive sensory nerves including vagal afferents. Ip injection of butyrate induced significant phosphorylation of extracellular-signal-regulated kinase 1/2, cellular activation markers, in nodose ganglia and their projection site, medial nucleus tractus solitaries. Moreover, butyrate directly interacted with single neurons isolated from nodose ganglia and induced intracellular Ca2+ signaling. The present results identify the vagal afferent as the novel pathway through which exogenous SCFAs execute the remote control of feeding behavior and possibly other brain functions. Vagal afferents might participate in suppression of feeding by intestine-born SCFAs.

La vaginotomía percutánea en la tendovaginitis estenosante de los dedos largos de las manos / La ténotomie percutanée dans le traitement de la ténosynovite sténosante des doigts longs de la main / Percutaneous vaginotomy in stenosing tendovaginitis of hand long fingers

Introducción: La tendovaginitis estenosante de los dedos de la mano o dedo en resorte es una patología relativamente frecuente que puede afectar a personas durante su vida laboral. Existen diversos métodos para solucionar esta afección. Objetivo: Evaluar el empleo durante ocho años de la vaginotomía percutánea en la tendovaginitis estenosante de los dedos largos de las manos. Métodos: Se realizó un estudio de intervención longitudinal prospectivo con adultos mayores de 65 años de edad. La muestra estuvo constituida por 468 pacientes diagnosticados con tendovaginitis estenosante (dedo en resorte). Fueron intervenidos quirúrgicamente 532 dedos con la vagotomía percutánea entre el 1 de enero de 2008 y el 31 de octubre de 2015, en el Centro de Investigaciones en Longevidad, Envejecimiento y Salud. Se evaluaron los pacientes seis meses después del tratamiento. Las variables empleadas fueron: edad, sexo, tiempo de padecimiento, dedo afectado, tiempo quirúrgico, complicaciones perioperatorias, duración del dolor. Se utilizó la clasificación de Newport según el cuadro clínico y el método de Strickland para evaluar los resultados. Resultado: Hubo un predomino del sexo femenino en la sexta década de vida. Las mayores incidencias estuvieron en la mano dominante. Se obtuvo un 98,3 por ciento de resultados satisfactorios. Los tiempos promedios de las variables descritas fueron significativamente cortos. No se mostraron complicaciones serias. Los dedos más afectados fueron el cuarto y el tercero. Hubo predominio de los estadios II y III. Conclusión: La vaginotomía percutánea solucionó satisfactoriamente la morbilidad que produce el dedo en resorte(AU)

Introduction: Stenosing tendovaginitis of hand fingers or spring finger is a relatively frequent pathology that can affect people during their working life. There are several methods to solve this condition. Objective: To evaluate the used of percutaneous vaginotomy in stenosing tendovaginitis of the long fingers for eight years. Methods: A prospective longitudinal intervention was conducted with adults over 65 years of age. 468 patients formed the sample. They were diagnosed with stenosing tendovaginitis (spring finger). Surgery was performed on 532 fingers with percutaneous vagotomy from January 1, 2008 to October 31, 2015, at the Research Center on Longevity, Aging and Health. Patients were assessed six months after treatment. The variables used were age, sex, time of suffering, affected finger, surgical time, perioperative complications, and duration of pain. Newport classification was used according to the symptoms and Strickland method to assess the results. Result: There was predominance of the female sex in their sixth decade of life. The highest incidences were in the dominant hand. Satisfactory results were 98.3 percent. The average times of the variables described were significantly short. No serious complications were shown. The most affected fingers were the fourth and the third. There was predominance of stages II and III. Conclusion: Percutaneous vaginotomy satisfactorily resolved the morbidity produced by the spring finger(AU)

Introduction: La ténosynovite sténosante des doigts de la main, ou doigt à ressort, est une pathologie assez fréquente pouvant affecter les personnes tout au long de leur vie. Il y a plusieurs méthodes pour corriger cette affection. Objectif: Évaluer l'utilisation pendant huit ans de la ténotomie percutanée pour corriger la ténosynovite sténosante des doigts longs de la main. Méthodes: Une étude interventionnelle, longitudinale et prospective des personnes âgées de plus de 65 ans a été effectuée. L'échantillon a été composée de 468 patients diagnostiqués de ténosynovite sténosante (doigt à ressort). Un nombre significatif d'interventions chirurgicales (532 doigts) ont été effectuées entre le 1 janvier 2008 et le 31 octobre 2015 au Centre de recherches sur la longévité, le vieillissement et la santé. Les patients ont été évalués six mois après le traitement. On a utilisé des variables telles que l'âge, le sexe, la durée de l'affection, le doigt affecté, le temps chirurgical, les complications péri-opératoires, et la durée de la douleur. Afin d'évaluer les résultats, on a appliqué la classification de Newport, selon le tableau clinique et la méthode de Strickland. Résultats: On a trouvé que les femmes dans les soixante ans étaient les plus souvent touchées par cette affection, étant la main dominante la plus affectée. Il y a eu de très bons résultats (98.3 pourcent). Les temps moyens des variables décrites ont été notamment courts. Il n'y a pas eu de complications graves. Le troisième et le quatrième doigt ont été les plus fréquemment touchés. Dans la classification, le stade II et III ont été en prédominance. Conclusions: La ténotomie percutanée a réussi à corriger de manière satisfaisante la morbidité provoquée par le doigt à ressort(AU)

Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence.

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

Complexity of Stomach-Brain Interaction Induced by Molecular Hydrogen in Parkinson's Disease Model Mice.

Molecular hydrogen (H2), as a new medical gas, has protective effects in neurological disorders including Parkinson's disease (PD). In our previous report, the neuroprotective effect of drinking water with saturated H2 (H2 water) in PD mice might be due to stomach-brain interaction via release of gastric hormone, ghrelin. In the present study, we assessed the effect of H2-induced ghrelin more precisely. To confirm the contribution of ghrelin in H2 water-drinking PD model mice, ghrelin-knock out (KO) mice were used. Despite the speculation, the effect of H2 water was still observed in ghrelin-KO PD model mice. To further check the involvement of ghrelin, possible contribution of ghrelin-induced vagal afferent effect was tested by performing subdiaphragmatic vagotomy before treating with H2 water and administration of MPTP (1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine). The protective effect of H2 water was still observed in the vagotomized mice in substantia nigra, suggesting that stimulation of vagal afferent nerves is not involved in H2-induced neuroprotection. Other neuroprotective substitutes in ghrelin-KO mice were speculated because H2-induced neuroprotection was not cancelled by ghrelin receptor antagonist, D-Lys3 GHRP-6, in ghrelin-KO PD model mice, unlike in wild-type PD model mice. Our results indicate that ghrelin may not be the only factor for H2-induced neuroprotection and other factors can substitute the role of ghrelin when ghrelin is absent, raising intriguing options of research for H2-responsive factors.

Effect of vagotomy on the activity of cardiac autonomic ganglia: Insight from left atrial high density frequency mapping.

BACKGROUND: Both extrinsic and intrinsic cardiac autonomic nervous systems are important for initiation and maintenance of atrial fibrillation (AF). We aimed to evaluate the effect of vagotomy on the activity of cardiac autonomic ganglionated plexi (GP) and the change of dominant frequency (DF) distribution in the left atrium (LA) during AF. METHODS: A mid-sternal thoracotomy was performed in 6 dogs. High frequency stimulation was applied to locate the GPs. There were four major LA GPs, which were located near the pulmonary vein ostia, and a superior vena cava-aorta (SVC-Ao) GP that was located near the superior vena cava-right atrial junction. Acetylcholine patch was applied on GPs to induce intrinsic vagal response. Vagal denervation was performed thereafter. An Ensite Array was deployed in the LA to record atrial signals before and after vagotomy during induced AF. RESULTS: The LA mean DF values (8.2±0.1 vs. 7.6±0.1Hz, p=0.002) were higher during GP activation before than after vagotomy. The maximal DF distribution was located at the primary GPs and the nearby secondary GPs during LA GPs activation and at the LA septum and right superior pulmonary vein during SVC-Ao GP activation before vagotomy. After vagotomy, the maximal DF distribution shifted to non-GP LA sites during activation of the GPs. CONCLUSIONS: The findings suggest the important role of the extrinsic neural input in the activation and interaction of the intrinsic cardiac autonomic activity during cholinergic AF, whereas the non-GP LA sites were responsible for the AF induced without the physiological extrinsic neural input.

The insulinotropic effect of exogenous glucagon-like peptide-1 is not affected by acute vagotomy in anaesthetized pigs.

What is the central question of this study? We investigated whether intestinal vagal afferents are necessary for the insulinotropic effect of glucagon-like peptide-1 (GLP-1) infused into a mesenteric artery or a peripheral vein before and after acute truncal vagotomy. What is the main finding and its importance? We found no effect of truncal vagotomy on the insulinotropic effect of exogenous GLP-1 and speculate that high circulating concentrations of GLP-1 after i.v. and i.a. infusion might have overshadowed any neural signalling component. We propose that further investigations into the possible vagal afferent signalling of GLP-1 would best be pursued using enteral stimuli to provide high subepithelial levels of endogenous GLP-1. Glucagon-like peptide 1 (GLP-1) is secreted from the gut in response to luminal stimuli and stimulates insulin secretion in a glucose-dependent manner. As a result of rapid enzymatic degradation of GLP-1 by dipeptidyl peptidase-4, a signalling pathway involving activation of intestinal vagal afferents has been proposed. We conducted two series of experiments in α-chloralose-anaesthetized pigs. In protocol I, pigs (n = 14) were allocated for either i.v. or i.a. (mesenteric) GLP-1 infusions (1 and 2 pmol kg(-1)  min(-1) , 30 min) while maintaining permissive glucose concentrations at 6 mmol l(-1) by i.v. glucose infusion. The GLP-1 infusions were repeated after acute truncal vagotomy. In protocol II, pigs (n = 27) were allocated into six groups. Glucagon-like peptide 1 was infused i.v. or i.a. (mesenteric) for 1 h at 3 or 30 pmol kg(-1)  min(-1) . During the steady state (21 min into the GLP-1 infusion), glucose (0.2 g kg(-1) , i.v.) was administered over 9 min to stimulate ß-cell secretion. Thirty minutes after the glucose infusion, GLP-1 infusions were discontinued. Following a washout period, the vagal trunks were severed in four of six groups (vagal trunks were left intact in two of six groups), whereupon all infusions were repeated. We found no effect of vagotomy on insulin or glucagon secretion during administration of exogenous GLP-1 in any experiment. We speculate that the effect of exogenous GLP-1 overshadowed any effect occurring via the vagus. Within dosage groups, total GLP-1 concentrations were similar, but intact GLP-1 concentrations were much lower when infused via the mesenteric artery because of extensive degradation of GLP-1 in the splanchnic bed. This demonstrates the effectiveness with which intestinal capillary dipeptidyl peptidase-4 protects the systemic circulation from intact GLP-1, consistent with a local role for GLP-1 involving activation of vagal pathways.

Mechanisms of airway responses to esophageal acidification in cats.

Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 µg·kg(-1)·30 min(-1) iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa. We found that vagotomy or atropine blocked the airway constriction response but only atropine blocked the increase in mucous output and decrease in mucociliary transport rate caused by esophageal acidification. The mucous cells of the mucosa produced more Alcian blue- than periodic acid-Schiff (PAS)-stained mucosubstances, and the mucous cells of the submucosa produced more PAS- than Alcian blue-stained mucosubstances. Selective perfusion of the different segments of esophagus with HCl or PBS resulted in significantly greater production of PAS-stained mucus in the submucosa of the trachea adjacent to the HCl-perfused esophagus than in that adjacent to the PBS-perfused esophagus. In conclusion, airway constriction caused by esophageal acidification is mediated by a vagal cholinergic pathway, and the tracheobronchial transport response is mediated by cholinergic receptors. Acid perfusion of the esophagus selectively increases production of neutral mucosubstances of the apocrine glands by a local mechanism. We hypothesize that the airway responses to esophageal acid exposure are part of the innate, rather than acute emergency, airway defense system.