Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis.

Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. Methods: Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n â€‹= â€‹9) or sham VGX (non-VGX, n â€‹= â€‹6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. Results: At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p â€‹= â€‹0.055; stance time imbalance â€‹= â€‹1.6 â€‹± â€‹1.6%) and shifted foot strike locations (p â€‹< â€‹0.001; spatial symmetry â€‹= â€‹48.4 â€‹± â€‹0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 â€‹± â€‹7.70 compared to the non-VGX animal sensitivity of 29.74 â€‹± â€‹9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p â€‹= â€‹0.076; VGX: 0.80 â€‹± â€‹0.036 â€‹mm2; non-VGX: 0.736 â€‹± â€‹0.066 â€‹mm2). No group differences in systemic inflammation were observed at endpoint. Conclusions: VGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.

Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.

Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4+Iba1+, TLR2+Iba1+, and NF-κB+Iba1+ cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.

Vagus nerve damage increases alcohol intake and preference in a nonpreferring rat line: Relationship to vagal regulation of the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Clinical and preclinical research indicates that gastric weight loss surgeries, such as Roux-en-Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake. METHODS: To test this hypothesis, we compared alcohol intake and preference in multiple models in male Sprague-Dawley rats that received selective gastric branch vagotomy (VX) with rats who underwent sham surgery. Because the vagus nerve regulates hypothalamic-pituitary-adrenal (HPA) axis function, and alterations to HPA function are critical to the escalation of non-dependent alcohol intake, we also tested the hypothesis that gastric VX increases HPA function. RESULTS: We found that VX increases alcohol intake and preference in the every-other-day, two-bottle choice test and increases preference for 1 g/kg alcohol in the conditioned place preference test. The effects were selective for alcohol, as sucrose intake and preference were not altered by VX. We also found that VX increases corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN), increases putative PVN CRF neuronal action potential firing, and increases corticosterone levels. CONCLUSIONS: Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of PVN CRF mRNA expression and putative PVN CRF neuronal activity. Furthermore, disruptions to vagal regulation of HPA axis function may increase alcohol intake and preference.

Surgical Management of Upper Gastrointestinal Bleeding.

The use of surgery in managing upper gastrointestinal (GI) bleeding has rapidly diminished secondary to advances in our understanding of the pathologies that underlie upper GI bleeding, pharmaceutical treatments for peptic ulcer disease, and endoscopic procedures used to gain hemostasis. A surgeon must work collaboratively with gastroenterologist and interventional radiologist to determine when, and what kind of, surgery is appropriate for the patient with upper GI bleeding.

Hepatic Vagotomy in Patients With Obesity Leads to Improvement of the Cholesterol to High-Density Lipoprotein Ratio.

INTRODUCTION/PURPOSE: The obesity epidemic is rapidly growing, and visceral adiposity is associated with metabolic consequences secondary to peroxisome proliferator-activated receptor (PPAR)-induced inter-organ signaling pathways. PPARs are ligand-activated transcription factors that modulate vagal pathways which can improve blood pressure, arterial remodeling, cholesterol levels, and insulin sensitivity. However, an obesity-induced inflammatory milieu can interfere with the beneficial effects of PPAR activity, suggesting that a dysregulated PPAR-vagus pathway may play a role in the pathogenesis of obesity-related hypertension. Therefore, we hypothesized that hepatic vagotomy (HV) in patients with obesity would result in a significant reduction in blood pressure and/or the number of hypertension medications compared to control. METHODS: We conducted a retrospective chart review of 160 patients undergoing laparoscopic sleeve gastrectomy. Patients were divided into HV and control groups, and information was collected at each clinic visit. RESULTS: At six-months post-operation, the HV group was found to have significantly lower total cholesterol (TC)/high-density lipoprotein (HDL) ratios than the control group. The HV group also had a numerically better blood profile for TC, HDL, low-density lipoprotein (LDL), triglycerides, C-reactive protein, and LDL/HDL ratio. Hypertensive patients in the HV group showed numerically lower hypertension medication counts after six weeks when compared to control. CONCLUSION: We present the first study to report clinically significant changes related to HV in human subjects. Our results did not support our initial hypothesis but did demonstrate an improvement of the TC/HDL ratio with HV in patients with obesity. Future studies should confirm these findings in a randomized control trial.

Concurrent laparoscopic highly selective vagotomy with closure of duodenal ulcer perforations show good clinical results as primary repair alone.

OBJECTIVE: To compare clinical and operative results between laparoscopic primary repair (LPR) alone and LPR with highly selective vagotomy (LPR-HSV) in patients with duodenal ulcer perforation. METHODS: Clinical data from patients who underwent either LPR or LPR-HSV by resecting both sides of the neurovascular bundle using an ultrasonic or bipolar electrosurgical device for duodenal ulcer perforations, between 2010 and 2020, were retrospectively collected. Between-group differences in continuous and categorical variables were statistically analysed. RESULTS: Data from 184 patients (mean age, 49.6 years), who underwent either LPR (n = 132) or LPR-HSV (n = 52) were included. The mean operation time was significantly longer in the LPR-HSV group (116.5 ± 39.8 min) than in the LPR group (91.2 ± 33.3 min). Hospital stay was significantly shorter in the LPR-HSV group (8.6 ± 2.6 days) versus the LPR group (11.3 ± 7.1 days). The mean postoperative day of starting soft fluid diet was also significantly shorter in the LPR-HSV group (4.5 ± 1.4 days) than in the LPR group (5.6 ± 4 days). No between-group difference in morbidity rate was observed. The learning curve of the HSV procedure showed a stable procedure time after 10 operations. CONCLUSIONS: LPR with HSV may be a safe and feasible procedure for selective cases who are at high risk for ulcer recurrence.

Clinicopathological Predisposing Factors for Gastric Stump Cancer and Its Management: A Single-Center Analytical Study.

Background The incidence of gastric stump carcinoma (GSC) is not declining because of the long latency period. The survival rate of treated gastric cancer patients has increased due to early detection and improvements in surgical techniques and chemotherapy. Increased survival rates and improved surveillance following gastric surgery have increased the incidence of GSC. Aim The study aims to investigate the clinicopathological factors affecting the interval between index gastric surgery and the occurrence of GSC, and our experience in the management of GSC is presented. Methods A retrospective review of patients diagnosed with GSC in our institution was completed. Patient characteristics and clinicopathological outcomes were analyzed. Results A total of 28 patients were included in this cohort with 17 (60.71%) males and 11 (39.28%) females. The mean interval from index surgery to the incidence of GSC was 24.42 years for benign etiology and six years for malignant etiology. Index surgeries were truncal vagotomy with 14 gastrojejunostomies (50%) and 14 subtotal gastrectomies (50%). The interval between index surgery and the incidence of GSC is not statistically significant concerning the type of surgery (p: 0.661), pathological TNM (tumor, nodes, metastases) stage (p: 0.520), pathological differentiation (p: 0.828), lymphovascular invasion (p: 0.252), perineural invasion (p: 0.672), and adjuvant therapy (p: -0.655). Survival was significantly higher in those patients who received curative resection in comparison to a palliative procedure (p: 0.041). Conclusion Strict surveillance for at least 10 years after initial gastric surgery is of utmost importance as half of the patients fated to develop GSC will do so within this time. In those patients with early diagnosis, no evidence of metastasis, and good performance status, curative surgery is feasible with acceptable morbidity.

Is vagotomy necessary in palliative surgery for incurable advanced gastric cancer?: a retrospective case-control study.

BACKGROUND: The interplay between the nervous system and cancer plays an important role in the initiation and progression of gastric cancer. Few studies have presented evidence that the sympathetic nervous system inhibits the occurrence and development of gastric cancer while the parasympathetic nervous system promotes the growth of gastric cancer. To investigate the effect of vagotomy, which is the resection of a parasympathetic nerve innervating the stomach, on the progression of gastric cancer, a retrospective study was conducted comparing the prognosis of simple palliative gastrojejunostomy (PGJ) and palliative gastrojejunostomy with vagotomy (PGJV). METHODS: From January 01, 2000, to December 31, 2021, the medical records of patients who underwent PGJ or PGJV because of gastric outlet obstruction due to incurable advanced gastric cancer at the Yeungnam University Medical Center were retrospectively reviewed. Patients were divided into two groups: locally unresectable gastric cancer (LUGC) or gastric cancer with distant metastasis (GCDM), according to the reason for gastrojejunostomy, and factors affecting overall survival (OS) were analyzed. RESULTS: There was no significant difference in surgical outcomes and postoperative complications between the patients with PGJV and patients with PGJ. In univariate analysis, vagotomy was not a significant factor for OS in the GCDM group (HR 1.14, CI 0.67-1.94, p value 0.642), while vagotomy was a significant factor for OS in the LUGC group (HR 0.38, CI 0.15-0.98, p value 0.045). In multivariate analysis, when vagotomy is performed together with PGJ for LUGC, the OS can be significantly extended (HR 0.25, CI 0.09-0.068, p value 0.007). CONCLUSIONS: When PGJ for LUGC was performed with vagotomy, additional survival benefits could be achieved with low complication risk. However, to confirm the effect of vagotomy on the growth of gastric cancer, further prospective studies using large sample sizes are essential.

GLP-1 Increases Circulating Leptin Levels in Truncal Vagotomized Rats.

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.

Exploring the Modulatory Effect of High-Fat Nutrition on Lipopolysaccharide-Induced Acute Lung Injury in Vagotomized Rats and the Role of the Vagus Nerve.

During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (p > 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an α7nAChR-agonist (p = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (p = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (p = 0.012) and selective vagotomy (p = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy.

A Critical Involvement of Glutamatergic Neurons in the Anterior Insular Cortex for Subdiaphragmatic Vagotomy-induced Analgesia.

Subdiaphragmatic vagotomy (SDV) is known to produce analgesic effect in various pain conditions including not only visceral pain but also somatic pain. We aimed to determine brain mechanisms by which SDV induces analgesic effect in somatic pain condition by using formalin-induced acute inflammatory pain model. We identified brain regions that mediate SDV-induced analgesic effect on acute inflammatory pain by analyzing c-Fos expression in the whole brain. We found that c-Fos expression was specifically increased in the anterior insular cortex (aIC) among subregions of the insular cortex in acute inflammatory pain, which was reversed by SDV. These results were not mimicked in female mice, indicating sexual-dimorphism in SDV-induced analgesia. SDV decreased c-Fos expressions more preferentially in glutamatergic neurons rather than GABAergic neurons in the aIC, and pharmacological activation of glutamatergic neurons with NMDA in the aIC inhibited SDV-induced analgesic effect. Furthermore, chemogenetic activation of glutamatergic neurons in the aIC reversed SDV-induced analgesia. Taken together, our results suggest that the decrease in the neuronal activity of glutamatergic neurons in the aIC mediates SDV-induced analgesic effect, potentially serving as an important therapeutic target to treat inflammatory pain.

Vagus innervation in the gastrointestinal tumor: Current understanding and challenges.

The vagus nerve (VN) is the main parasympathetic nerve of the autonomic nervous system. It is widely distributed in the gastrointestinal tract and maintains gastrointestinal homeostasis with the sympathetic nerve under physiological conditions. The VN communicates with various components of the tumor microenvironment to positively and dynamically affect the progression of gastrointestinal tumors (GITs). The intervention in vagus innervation delays GIT progression. Developments in adeno-associated virus vectors, nanotechnology, and in vivo neurobiological techniques have enabled the creation of precisely regulated "tumor neurotherapies". The present review aimed to summarize the mechanisms of communication between the VN and the gastrointestinal TME and to explore the potential and challenges of VN-based tumor neurotherapy in GITs.

Auricular Vagus Nerve Stimulation Improves Visceral Hypersensitivity and Gastric Motility and Depression-like Behaviors via Vago-Vagal Pathway in a Rat Model of Functional Dyspepsia.

Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD. METHODS: We evaluated the effects of aVNS on visceral hypersensitivity, gastric motility and open field test (OFT) activity in iodoacetamide (IA)-treated rats. The autonomic function was assessed; blood samples and tissues were collected and analyzed by an enzyme-linked immunosorbent assay and western blot. Vagotomy was performed to investigate the role of vagal efferent nerve. RESULTS: aVNS reduced the electromyography response to gastric distension, improved gastric emptying and increased the horizontal and vertical motion scores of the OFT in IA-treated rats. The sympathovagal ratio was increased in IA-treated rats but normalized with aVNS. The serum cytokines TNF-α, IL-6, IL-1ß and NF-κBp65 were increased in IA-treated rats and decreased with aVNS. The hypothalamus-pituitary-adrenal axis was hyperactive in IA-treated rats but inhibited by aVNS. The expression of duodenal desmoglein 2 and occludin were all decreased in IA-treated rats and increased with aVNS but not sham-aVNS. Vagotomy abolished the ameliorating effects of aVNS on gastric emptying, horizontal motions, serum TNF-α and duodenal NF-κBp65. CONCLUSION: aVNS improves gastric motility and gastric hypersensitivity probably by anti-inflammatory mechanisms via the vago-vagal pathways. A better understanding on the mechanisms of action involved with aVNS would lead to the optimization of the taVNS methodology and promote taVNS as a non-pharmacological alternative therapy for FD.

The effects of gallic acid and vagotomy on motor function, intestinal transit, brain electrophysiology and oxidative stress alterations in a rat model of Parkinson's disease induced by rotenone.

INTRODUCTION: The neuropathology of Parkinson's disease (PD) is complex and affects multiple systems of the body beyond the central nervous system. This study examined the effects of gallic acid (GA) and gastrointestinal vagotomy (VG) on motor, cognitive, intestinal transit time, and thalamic nuclei electrical power in an animal model of PD induced by rotenone. MATERIALS AND METHODS: Male Wistar rats were divided into 4 groups: Sham, ROT, ROT+GA, VG + ROT. Sham rats received vehicle, those in ROT received rotenone (5 mg/kg/2 ml, ig), PD rats in ROT+GA were treated with GA (100 mg/kg, gavage/once daily, for 28 days), and in VG + ROT, the vagal nerve was dissected. Stride length, motor coordination and locomotion, intestinal transit time, cognitive and pain threshold, and thalamic local EEG were evaluated. Oxidative stress indexes in striatal tissue were also measured. RESULTS: Rotenone diminished significantly the stride length (p < 0.001), motor coordination (p < 0.001), power of thalamic EEG (p < 0.01) and pain (p < 0.001). MDA increased significantly (p < 0.001) while GPx activity decreased (p < 0.001). Intestinal transit time rose significantly (p < 0.01). PD rats treated with GA improved all above disorders (p < 0.001, p < 0.01). Vagotomy prevented significant alterations of motor and non-motor parameters by rotenone. CONCLUSION: According to current findings, rotenone acts as a toxin in GI and plays a role in the pathogenesis of PD through gastric vagal nerve. Thus, vagotomy could prevent the severity of toxicity by rotenone. In addition, GA improved symptoms of PD induced by rotenone. Therefore, GA can be regarded as a promising therapeutic candidate for PD patients.

Video- and Robotic-Assisted Thoracoscopic Truncal Vagotomy.

A subset of patients with marginal ulcers after Roux-en-Y gastric bypass (RNYGB) is refractory to medical management. Here we report a retrospective review of a single institution cohort (N = 10) of video- or robotic-assisted thoracoscopic (VATS or RATS) truncal vagotomies performed between 2013 and 2018. All patients had recurrent marginal ulcers following RNYGB complicated by bleeding or perforation, refractory to medical management for a median of 3.5 months prior to undergoing truncal vagotomy. With a median of 23 months' follow-up, only three patients had continued symptoms (70% symptom resolution) post-operatively. Only one patient who had repeat endoscopy after the procedure had documented endoscopic evidence of recurrent marginal ulcer (83% endoscopic resolution). VATS or RATS truncal vagotomy is a safe and effective method to treat complicated marginal ulceration after RNYGB. After an average duration of unsuccessful medical treatment lasting three months, vagotomy led to successful resolution in 70-83% of patients.

Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22.

BACKGROUND: Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe, effective, and stable drugs to promote liver regeneration. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism at play here is not fully understood. AIM: To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx. METHODS: A PHx plus hepatic vagotomy (Hv) mouse model was established. The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. In order to further investigate the role of interleukin (IL)-22 in liver regeneration inhibition mediated by Hv, the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured. The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx. RESULTS: Compared to control-group mice, Hv mice showed severe liver injury and weakened liver regeneration after PHx. Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3 (STAT3) pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx. Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury, while treatment with IL-22 binding protein (an inhibitor of IL-22 signaling) reduce the concentration of IL-22 induced by PHx, inhibits the activation of the STAT3 signaling pathway in the liver after PHx, thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice. CONCLUSION: Hv attenuates liver regeneration after hepatectomy, and the mechanism may be related to the fact that Hv downregulates the production of IL-22, then blocks activation of the STAT3 pathway.

Effect of Physical Training on the Morphology of Parasympathetic Atrial Ganglia after Unilateral Vagotomy in Rats.

Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after crossing the preganglionic fibers of the vagus nerve has not been enough studied. The aim of our study was to assess the effect of physical training on the morphological parameters of the parasympathetic atrial ganglia and autonomic regulation of heart rate after right- and left-sided vagotomy in rats. Morphometric characteristics of the right atrial ganglia were evaluated using an immunohistochemical method after a study that included a three-time assessment of heart rate variability. It was found that right-sided vagotomy leads to both an increase in the volume of ganglion and autonomic dysfunction. No significant change in the number of nerve cells was found in animals with false and left-sided vagotomy while maintaining preganglionic innervation after the physical training, whereas exercises led to a decrease in the volume of nerve tissue of rats with right-sided denervation. It was also found that in animals with preserved vagal innervation, the volume of atrial ganglion tissue correlates with overall heart rate variability and a normalized parasympathetic component. Therefore, a positive effect from regular physical activity on parasympathetic regulation can be expected only if preganglionic vagal influence is preserved.

Marginal Ulcer Perforation in a Whipple Survivor: A Rare Long-Term Complication.

Long-term complications following pancreaticoduodenectomy are rarely reported because of the poor long-term survival of these patients. Marginal ulcers can occur in both the short and long term, and they can become complicated by bleeding or perforation. Marginal ulcer with perforation is a rare incidence and only sparse literature evidence is available. Herein, we report on a patient who underwent pancreaticoduodenectomy 12 years ago for duodenal adenocarcinoma and was diagnosed to have perforation peritonitis. He underwent emergency laparotomy and lavage, and omental patch closure for marginal ulcer perforation at the gastrojejunostomy site. Truncal vagotomy and feeding jejunostomy were also done.

Hypothalamic Neurochemical Changes in Long-Term Recovered Bilateral Subdiaphragmatic Vagotomized Rats.

Background: Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone - a marker of hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus. Materials and Methods: Using microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery. Results: Our results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes. Discussion: We propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission.

Metabolic effects of truncal vagotomy when combined with bariatric-metabolic surgery.

Bariatric-metabolic surgery (BMS) in patients with obesity frequently leads to remission of concurrent type 2 diabetes mellitus (T2DM), even before body weight loss takes place. This is probably based on the correction of a dysmetabolic cycle in the gastrointestinal physiology of T2DM that includes increased vagus-dependent exocrine pancreatic secretion (EPS) and, hence, amplified digestion and nutrient absorption. The resultant chronic exposure of tissues to high plasma levels of glucose, fatty acids and amino acids causes tissue resistance to the actions of insulin and, at a later stage, ß-cell dysfunction and reduction of insulin release. We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS, - hence reducing the digestion and absorption of nutrients -, and increasing incretin secretion as a result of increased delivery of unabsorbed nutrients to the distal intestine. This hypothesis is supported by surgical data from gastrointestinal malignancies and peptic ulcer operations that include TV, as well as by vagal blockade studies. We suggest that TV may result in a stable reduction of EPS, and that its combination with the appropriate type of BΜS, may enhance and sustain the salutary effects of the latter on T2DM.