Gastric Dysmotility Research Articles

Autonomic function, postprandial hypotension and falls in older adults at one year after critical illness

Postprandial hypotension occurs frequently in older survivors of critical illness at 3 months after discharge. We aimed to determine whether postprandial hypotension and its predictors - gastric dysmotility and cardiovascular autonomic dysfunction - persist or resolve as older survivors of critical illness recover, and whether postprandial hypotension after intensive care unit (ICU) discharge is associated with adverse outcomes at 12 months. Prospective observational study. Tertiary medical-surgical ICU. Older adults (aged ≥ 65 years) who had been studied 3 months after ICU discharge and who returned for a follow-up study at 12 months after discharge. On both occasions after fasting overnight, participants consumed a 300 mL drink containing 75 g glucose, radiolabelled with 20 MBq 99mTcphytate. Blood pressure, heart rate, blood glucose concentration and gastric emptying rate were measured concurrently before and after ingestion of the drink. Falls, quality of life, hospitalisation and mortality rates were also quantified. Out of 35 older adults studied at 3 months, 22 returned for the follow-up study at 12 months. Postprandial hypotension was evident in 29% of participants (95% CI, 14-44%) at 3 months and 10% of participants (95% CI, 1-30%) at 12 months. Postprandial hypotension at 3 months was associated with a more than threefold increase in the risk of falls in the year after ICU discharge (relative risk, 3.7 [95% CI, 1.6-8.8]; P = 0.003). At 12 months, gastric emptying was normal (mean time taken for 50% of gastric contents to empty, 101.6 [SD, 33.3] min) and cardiovascular autonomic dysfunction prevalence was low (9% [95% CI, 1-29%]). In older adults who were evaluated 3 and 12 months after ICU discharge, postprandial hypotension at 3 months was associated with an increased risk of subsequent falls, but the prevalence of postprandial hypotension decreased with time.

Upregulation of gastric norepinephrine with beta-adrenoceptors and gastric dysmotility in a rat model of functional dyspepsia.

Disordered motility is one of the most important pathogenic characteristics of functional dyspepsia (FD), although the underlying mechanisms remain unclear. Since the sympathetic system is important to the regulation of gastrointestinal motility, the present study aimed to investigate the role of norepinephrine (NE) and adrenoceptors in disordered gastric motility in a rat model with FD. The effect of exogenous NE on gastric motility in control and FD rats was measured through an organ bath study. The expression and distribution of beta-adrenoceptors were examined by real-time PCR, Western blotting and immunofluorescence. The results showed that endogenous gastric NE was elevated in FD rats, and hyperreactivity of gastric smooth muscle to NE and delayed gastric emptying were observed in the rat model of FD. The mRNA levels of beta1-adrenoceptor and norepinephrine transporter (NET) and the protein levels of beta2-adrenoceptor and NET were increased significantly in the gastric corpus of FD rats. All three subtypes of beta-adrenoceptors were abundantly distributed in the gastric corpus of rats. In conclusion, the enhanced NE and beta-adrenoceptors and NETs may be contributed to the disordered gastric motility in FD rats.

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs.

BackgroundMemantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG).MethodsSix adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes).ResultsSingle dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280–1312 μV^2) raised after 15 min. (median 827; IQR 224–2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695–15023 μV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328–2280 μV^2; p<0.001), lasting till 120 min. (p<0.001).ConclusionsBoth single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.

RELATIONSHIP BETWEEN HELICOBACTER PYLORI INFECTION IN TYPE 2 DIABETES MELLITUS PATIENTS BASED ON ANTI IgA AND ANTI IgG HELICOBACTER PYLORI

Background Helicobacter Pylori (H. Pylori) infection is an infectious disease of the gastrointertinal tract especially the stomach and is currently associated with various systemic disorders in the body, one of which is hormonal disorders. Diabetes mellitus (DM) is an important cause of dyspepsia. Impaired gastrointestinal motor function is now recognized as a major problem in diabetes mellitus. The incidence of H. Pylori is increased in DM. Delayed gastric emptying and dysmotility are important causes of dyspepsia in diabetes. Methods This study was conducted by cross sectional method. The sample of the study was 39 patients who met the inclusion and exclusion criteria in the General Hospital H. Adam Malik Medan. Anti IgA and anti IgG H. Pylori examination by ELISA method using Chemwell. Results There were no difference in the incidence of anti IgA H. Pylori positive in patients with controlled DM and uncontrolled DM with p= 0,431. There was no difference in the incidence of anti IgA H. Pylori positive in patients with controlled DM and uncontrolled DM with p= 0,423. However, there were differences in H.Pylori infection in DM patients with dyspepsia and DM patients without dyspepsia with p = 0.001. Conclusion There were no relationship between H. Pylori infections in patients with type 2 DM.

Delayed gastric emptying in diabetic patients undergoing pancreaticoduodenectomy: A procedure-targeted nsqip analysis

Presenter: Alissa Greenbaum MD | Rutgers University Background: Delayed gastric emptying (DGE) is a major source of morbidity after pancreaticoduodenctomy (PD), occurring in up to 20% of patients. Patients with type I or II diabetes mellitus (DM) have a propensity for gastric dysmotility, however the exact relationship between DGE and DM is not clearly established. The aim of this study was to determine the incidence of DGE in patients with and without DM after PD. Methods: The American College of Surgeons National Quality Improvement Project (ACS-NSQIP) procedure-targeted pancreatectomy database was queried from 2014 to 2017 for patients undergoing PD and combined with the main ACS-NSQIP database. Patient demographic, clinical and perioperative variables were compared by DM status. The primary outcome was rate of DGE. A subset analysis of insulin-dependent DM (IDDM) and non-insulin-dependent DM (non-IDDM) patients was also performed. Statistical analyses were performed using chi-square, Mann Whitney-U tests, and logistic regression. Results: A total of 14,735 patients met inclusion criteria, including 10,930 non-DM patients (74.2%) and 3805 DM patients (25.8%). Median cohort age was 66 years and 53.7% were male (n=7918). DGE occurred in 17.1% of patients overall (n=2519); 17.2% in non-DM and 16.8% in DM patients (p=0.60). DM patients had a higher ASA class, increased rates of hypertension, increased proportion of pancreatic adenocarcinoma, larger duct size, harder gland texture, and required more frequent vascular resection (p<0.001). DM patients had equivalent rates compared to non-DM patients of post-operative superficial surgical site infection (7.8% in both; p=0.89), deep surgical site infection (1.4 vs 1.5%; p=0.56), urinary tract infection (3.2 vs 2.8%; p=0.23) and pneumonia (4.3 vs 3.6%; p=0.19), and lower rates of organ space infection (11.5 vs 14.0%; p<0.001) and pancreatic fistula (14.9 vs 19.0%; p<0.001). On subset analysis, IDDM had better outcomes compared to non-IDDM patients in organ space infections (8.8 vs 14.2%; p<0.001) and pancreatic fistula (11.7 vs 18.3%; p<0.001). Rates of DGE were 18.0% (n=337) in non-IDDM and 15.7% in IDDM patients (p=0.162). There were no significant differences in rates of reoperation, hospital length of stay, readmission rates or 30-day mortality. On multivariable logistic regression, male sex, advanced age, history of smoking, pancreatic fistula, and organ space infection were associated with DGE. DM status was not predictive of DGE. Conclusion: No differences in rates of DGE between DM and non-DM patients after PD were found, strengthening the hypothesis that DGE is a separate physiologic entity from diabetic gastroparesis. IDDM patients demonstrated better postsurgical outcomes compared to non-IDDM patients in terms of intra-abdominal infection and pancreatic fistula, suggesting a potential role of monitored insulin or hyperglycemia regulation in the development of these complications.

Is gastroparesis that is often detected in patients with alcoholic chronic liver disease a manifestation of an autonomic dysfunction syndrome? A preliminary study.

the autonomic dysfunction defines the neuropathy of the autonomic nervous system. The prevalence of the gastric dysmotility and its relationship with the autonomic dysfunction in patients with alcohol chronic liver disease is not well known. thirty-six patients with alcohol chronic liver disease and 25 healthy controls were evaluated, in order to detect an autonomic dysfunction through different cardiovascular reflexes and gastric emptying tests. ninety-four per cent of the patients showed an impaired R index (variations in heart rate during six deep inspirations-expirations per minute) and/or S/S-HR (variations in heart rate when standing from a supine position). Seventy-five per cent of the patients showed gastroparesis (T1/2: gastric half-emptying time was delayed). There was a correlation between the R index and T1/2 (r = -0.49; p < 0.01). we suggest that gastroparesis detected in alcoholic chronic liver disease is another clinical manifestation of the autonomic parasympathetic dysfunction.

Efficacy and Safety of Ghrelin Agonists in Patients with Diabetic Gastroparesis: A Systematic Review and Meta-Analysis.

Background/AimsGhrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG.MethodsA search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I2 statistics.ResultsWe selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, –0.34; 95% confidence interval, –0.56 to –0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies.ConclusionsCompared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG.

Mechanism of CNP-mediated DG-PKC and IP4 signaling pathway in diabetic rats with gastric motility disorder.

In the precedent research conducted by the same team, it concluded that the activities in C-type natriuretic peptide (CNP)/cyclic guanosine monophosphate (cGMP)/cyclic adenosine monophosphate (cAMP)/β-type phospholipase C (PLCβ) pathways of rat antral smooth muscle were changed due to diabetes, which was the key pathogenetic mechanism for diabetic gastric dysmotility. As the follow-on step, this study was designed to probe into the downstream signaling pathway of CNP/PLCβ. The results showed that level of α-type protein kinase C (PKCα),cell membrane to cytoplasm ratio of PKCα, cell membrane to cytoplasmic ratio of βI-type protein kinase C (PKCβI) and level of Phosphor-PKCα (P-PKCα) were significantly reduced in diabetes rat antral smooth muscle samples. The content of tetraphosphate inositol (IP4) in gastric antral smooth muscle of diabetic rats reduced, and the content of diacyl-glycerol (DG) was unchanged. CNP significantly decreased the content of IP4 and DG, this effect was more obvious in diabetic rats. Subsequent to the addition of protein kinase A (PKA) blocker N-[2- (p-Bromocin-namylamino)ethyl]-5 -isoquinolinesulfonamide dihydrochloride (H-89) before CNP treatment, the inhibitory effect of CNP was reduced; subsequent to the addition of protein kinase G (PKG) blocker KT5823 before CNP treatment, the inhibitory effect of CNP was also reduced. With the addition of the combination of H-89 and KT5823 before CNP treatment, the inhibition by CNP could be offset. These results were concluded that CNP inhibited the activity of PKC family in rat smooth muscle and reduced the levels of IP4 and DG through the PKG/PKA-PLCβ pathways, causing inhibited muscular contractions, which may be a key pathogenetic factor for diabetic gastroparesis.

3247 Don't Clean the Stomach With a Kitchen Sponge: Case of a Kitchen Sponge Presenting as a Gastric Bezoar

INTRODUCTION: Gastric bezoars are rare and caused by ingestion of indigestible material. They are called polybezoars if resulted from the accumulation of ingested foreign bodies in the stomach. We present a rare case of a gastric polybezoar secondary to the ingestion of a kitchen sponge in a 53-year-old female which presented a significant endoscopic challenge during the removal. CASE DESCRIPTION/METHODS: A 53-year-old female with a history of major depressive disorder and multiple abdominal surgeries including gastric bypass was admitted for abdominal pain and vomiting for the last three days. Physical exam was remarkable for abdominal scars from prior surgeries. Initial laboratory data showed elevated blood urea nitrogen and creatinine. CT abdomen showed evidence of gastric bypass with a foreign body in the gastric remnant without any intestinal obstruction. On further questioning, she revealed that she had ingested the pieces of a kitchen sponge one week ago. An upper endoscopy was done which revealed an eight cm polybezoar made up of food material coating a sponge in the gastric pouch. The bezoar was fragmented using the biopsy forceps and removal was accomplished using Roth net and Trapezoid basket. An over tube was used to facilitate the repeated passages of the scope. The procedure lasted for two hours thus presenting a significant challenge. DISCUSSION: A gastric bezoar is defined as a foreign body resulting from the accumulation of ingested material in the stomach. It is a rare condition with the incidence of 0.4-4%. Depending on the type of the ingested material, it can be a phytobezoar (fibers), a trichobezoar (hair), a pharmacobezoar (medications), a polybezoar (foreign body) or a lactobezoar (milk product). Stomach is the most common site involved. Most bezoars are clinically asymptomatic due to large capacity of the stomach and are diagnosed incidentally on imaging or endoscopy done for other reasons. When symptomatic, they may present with epigastric pain, vomiting, hematemesis or small bowel obstruction. The major risk factors for the formation of the bezoars are conditions associated with gastric dysmotility, previous gastric surgery and psychiatric disorders. Complicated gastric bezoars impose a great challenge to an endoscopist. Several modalities have been suggested for the management of bezoar including chemical dissolution (sodium bicarbonate, Coca Cola lavage etc.) and endoscopic fragmentation with removal. Surgery is reserved for intestinal obstruction or a failed endoscopic treatment.

3248 SIBO and Gastroparesis: Downstream Effects of Diabetes

INTRODUCTION: Homeostasis of the GI mucosal environment depends on gut motility and normal gastric acid secretion. The autonomic nervous system plays an important role in these processes. Diabetes has been shown to injure the enteric nervous system, resulting in slowed motility. Gastroparesis and small intestinal bacterial overgrowth are two consequences of the enteric injury associated with diabetes. CASE DESCRIPTION/METHODS: A 23-year-old male with type 1 diabetes presented with 6 months of diffuse abdominal pain and diarrhea, which had recently worsened. He noted 4-6 loose bowel movements daily and vomiting after food. He had previously been seen by gastroenterology and had an unremarkable colonoscopy, EGD, and celiac testing. He had been trialed on rifaximin and neomycin, which improved his symptoms for a short period. He tried eluxadoline with little effect. On presentation, he was hemodynamically stable with labs significant only for mildly elevated AST (58 units/L). WBC, ESR, CRP, feces ova and parasites, and C. difficile Ag were all unremarkable. A gastric emptying study revealed moderate (24%) gastroparesis. A right upper quadrant ultrasound was unremarkable. Small intestinal bacterial overgrowth related to gastroparesis was suspected. A trial of rifaximin and metoclopramide improved his symptoms leading to empiric diagnosis of SIBO. DISCUSSION: Small intestinal bacterial overgrowth occurs when the normal homeostatic mechanisms that control bacterial populations are in some way disrupted. Frequently, this occurs with decreased gastric acid secretion or dysmotility of the small intestine. The most common symptoms of SIBO include bloating, abdominal discomfort and distention, chronic diarrhea, weight loss, and malabsorption. One proposed theory for SIBO in gastroparesis is the idea that phase 3 migratory motor complexes may be diminished in frequency or altogether absent. While the gold standard for diagnosis requires jejunal aspirate, lactulose and glucose breath testing have been used as indirect measures of SIBO. Multiple studies have been done to analyze the relationship between gastroparesis and SIBO with results showing up to 60-70% of study participants with gastroparesis test positive for SIBO via lactulose breath testing. Once the diagnosis of SIBO has been established, the goal of therapy is to correct the underlying cause, provide nutritional support, and treat overgrowth with a course of antibiotics.

2757 Gastric Amyloid: The Patient Who Could Not Eat at AL

INTRODUCTION: Gastroparesis is defined as delayed gastric emptying in the absence of mechanical obstruction. Diabetes and medication side effects are common causes. AL amyloidosis is a systemic disease due to extracellular fibril deposition that can affect multiple organs. Gastro-intestinal (GI) involvement is less common than in other organ systems but can present in many different ways, including gastroparesis. CASE DESCRIPTION/METHODS: A 77 year old non-diabetic man from Mississippi presented with a one year history of intermittent abdominal distention, nausea and bloating. In addition, he had increasing dyspnea on exertion and lower extremity edema. Outside work-up consisted of multiple imaging studies demonstrating marked gastric distention as well as delayed gastric emptying (Figures 1 and 2). Outside colonoscopy was unrevealing and EGD was negative except for a distal esophageal ulcer and focal active duodenitis. He was started on a PPI and trialed on an alternating regimen of metoclopramide and erythromycin, without symptomatic relief. He was referred to our hospital for further diagnostic work-up. Repeat colonoscopy showed congested distal ileal mucosa and friable ascending colonic mucosa. Biopsies from both sites revealed amyloid deposits by Congo red stain (Figure 3). Serum protein electrophoresis noted a monoclonal IgG lambda peak with M-spike of 1.5 g/dL and bone marrow biopsy revealed approximately 70% of marrow cellularity consisting of plasma cells. Echocardiogram confirmed severely increased concentric left ventricular wall thickening consistent with cardiac amyloidosis. Interestingly, neither fat pad biopsy nor bone marrow biopsy showed presence of amyloid. The patient was diagnosed with myeloma and AL amyloidosis with gastro-intestinal and cardiac involvement. DISCUSSION: This case highlights the broad differential for gastric distention and dysmotility. When the ‘usual suspects’ such as diabetes, medication, post-surgery and neurological disease have been ruled out, rarer causes like an infiltrative process should be considered. Common manifestations of GI tract amyloidosis include GI bleeding, malabsorption, protein-losing enteropathy and chronic dysmotility. The diagnosis of amyloidosis is based on positive tissue diagnosis. While the combination of a fat pad and a bone marrow biopsy has a high sensitivity (89%) for diagnosing AL amyloidosis, negative results do not rule out amyloid elsewhere and tissue sampling from the affected organ site is essential, as demonstrated in this case.

A Case Report of the Traditional Korean Treatment of Female Patients with Both Functional Dyspepsia and Chronic Atrophic Gastritis

Objective: The aim of this study was to introduce gastric dysmotility as a common cause in patients with concurrent functional dyspepsia and chronic atrophic gastritis. Method: Dyspeptic symptoms, the Rydoraku score, gastric motility (electrogastrography, bowel sound analysis), gastric mucosa (gastroendoscopy), and blood and blood chemistry were all evaluated. For the treatment method, Pyengwi-san (solution) and Banwhasashim-tang (extract) were used as herbal drugs. Both ST36 electrical stimulation and simple immersion stimulation of CV11, 12, and 13 in the abdomen were applied. Results: Dyspeptic symptoms including indigestion, headache, and insomnia were all relieved. Gastric myoelectrical activity and gastric pyloric function were additionally improved. The condition of the gastric mucosa was changed from atrophic to erosive. Other side-effects of the treatment were not noted. Conclusion: The traditional Korean treatment showed effectiveness in the relief of dyspeptic symptoms and mucosal improvement of chronic atrophic gastritis. Gastric dysmotility is a common cause of the condition being concurrent with both functional dyspepsia and chronic atrophic gastritis without Helicobacter pylori infection. Keywords: functional dyspepsia, gastric dysmotility, chronic atrophic gastritis, acupuncture, herbal medicine

Role of the Plasma Membrane Ca2+-ATPase Pump in the Regulation of Rhythm Generation by an Interstitial Cell of Cajal: A Computational Study

Gastrointestinal motility is based on the rhythmic activity of interstitial cells of Cajal (ICCs). The ICC rhythm generation relies upon characteristic Ca2+-handling mechanisms that involve voltage-gated Ca2+ channels, pumps and exchangers located in the plasma membrane, endoplasmic reticulum (ER), and mitochondria. Mutations, overexpression, and genetic knockdowns of the plasma membrane calcium ATPase (PMCA) pumps have been shown to disrupt calcium signaling and to cause disorders in other cell systems. Using an ICC biophysical model, we investigated the effects of PMCA pump upregulation in ICC rhythm generation. We found that, depending on the PMCA maximum pumping rate, the ICC model generates voltage and Ca2+ oscillations with different characteristics or becomes silent. The model predicts the coexistence of activity regimes near a canonical set of the parameters. One of these regimes is a silent regime that would indicate gastric dysmotility.

Any news from the prokinetic front?

This review provides an update of recently conducted studies and randomized controlled trials evaluating prokinetic drugs. Prokinetic drugs accelerate gastric emptying and, particularly in patients with gastric dysmotility and enteral feed intolerance, their use increases the delivery of enteral nutrition. However, prokinetic drugs have not been shown to improve patient-centered outcomes in trials but benefit is assumed on the basis of observational studies, which report close associations between gastric dysmotility, enteral feed intolerance and poor outcomes, and improvement in surrogate physiological outcomes when prokinetic drugs are administered. It may not be feasible to establish superiority of a prokinetic drug within a randomized controlled trial with a patient-centered event as the primary outcome. The use of metoclopramide and erythromycin as prokinetic drugs is based on observations from trials measuring surrogate physiological outcomes. Randomized controlled trials of alternative drug regimens and novel prokinetic drugs have recently been completed and results outlined.

Gastric dysmotility in Parkinson's disease is not caused by alterations of the gastric pacemaker cells

The enteric nervous system is involved in the pathology of Parkinson´s disease and patients frequently have symptoms related to delayed gastric emptying. However, the pathophysiology of gastric dysmotility is yet not well understood. The objective of this study was to assess interdigestive gastric motility in Parkinson´s disease. Using an electromagnetic capsule system, the dominant gastric contraction frequency (primary outcome measure) and the gastric transit time were assessed in 16 patients with Parkinson´s disease and 15 young healthy controls after a fasting period of 8 h. Motor and non-motor symptoms were assessed using the Movement Disorder Society Unified Parkinson´s Disease Rating Scale III (MDS-UPDRS III), the Non-Motor Symptoms Questionnaire (NMS-Quest), and Hoehn & Yahr staging. The Gastroparesis Cardinal Symptom Index was used to record symptoms related to delayed gastric emptying. In healthy controls and patients with Parkinson's disease, the dominant contraction frequency was 3.0 cpm indicating normal function of interstitial cells of Cajal. In patients with Parkinson's disease, the gastric transit time was longer than in younger controls (56 vs. 21 min). The dominant contraction frequency and gastric transit time did not correlate with age, disease duration, Hoehn & Yahr stage, levodopa equivalent daily dose, MDS-UPDRS III, NMS-Quest, and Gastroparesis Cardinal Symptom Index. Changes of gastric motility in Parkinson´s disease are not caused by functional deficits of the gastric pacemaker cells, the interstitial cells of Cajal. Therefore, gastroparesis in Parkinson's disease can be attributed to disturbances in neurohumoral signals via the vagus nerve and myenteric plexus.

Influence of the physical exercise on decrease in the gastric emptying and alter appetite and food behavior in rats dexamethasone-treatment

The chronic use of Dexamethasone (Dex) induced hyperglycemia and insulin resistance. On the other hand, physical exercise attenuates the symptoms induced by Dex in many physiological systems. However, the effect of the exercise on the changes in gastric motility induced by dexamethasone remains unknown. We hypothesized that low-intensity aerobic exercise modulates the metabolic effects induced by Dex-treatment by modifying the gastrointestinal function and feeding behavior in rats. Male rats were distributed into the following groups: Control (Ctrl), Dex (1.0 mg/kg, i.p.), Exercise (Ctrl + Exercise 5%) and (Dex1.0 + Exercise 5%). The exercise protocol was swimming for 5 consecutive days. We assessed the murinometric and nutritional indices, food intake, blood glucose by (ipGTT) and the gastric emptying rate of a liquid test meal were assessed in all rats. We observed a significant decrease (p < .05) in the gastric emptying in Dex1.0 group in relation to Ctrl group. The exercise prevented decrease in the gastric emptying (p < .05) in Dex1.0 + EX5% group when compared with Dex1.0 groups. The Dex1.0 group induced a significantly increase (p < .05) in glycaemia vs Ctrl group. The hyperglycemia was improving (p < .05) in the Dex1.0 + Ex5% compared with Dex1.0 groups. We observed a positive correlation (p < .05, and r = 0.7065) between gastric retention vs glycaemia in the Dex1.0 groups. The Dex1.0 reduced (p < .05) the body weight and altered body composition, promoting hypophagia. IL-6 increased (p < .05) at gastric fundus in Ex5% compared with Ctrl groups. In conclusion, the use of Dex1.0 decreases gastric emptying, promotes hyperglycemia and modifies feeding behavior. The low-intensity exercise prevents hyperglycemia, thus improving gastric dysmotility without improving the anthropometric parameters.

Radiographic dose-dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea-like behavior.

Loperamide is a potent mu opioid receptor agonist available over the counter to treat diarrhea. Although at therapeutic doses loperamide is devoid of central effects, it may exert them if used at high doses or combined with drugs that increase its systemic and/or central bioavailability. Recently, public health and scientific interest on loperamide has increased due to a growing trend of misuse and abuse, and consequent reports on its toxicity. Our aim was to evaluate in the rat the effects of increasing loperamide doses, with increasing likelihood to induce central effects, on gastrointestinal motor function (including gastric dysmotility and nausea-like behavior). Male Wistar rats received an intraperitoneal injection of vehicle or loperamide (0.1, 1, or 10mgkg-1 ). Three sets of experiments were performed to evaluate: (a) central effects (somatic nociceptive thresholds, immobility time, core temperature, spontaneous locomotor activity); (b) general gastrointestinal motility (serial X-rays were taken 0-8hours after intragastric barium administration and analyzed semiquantitatively, morphometrically, and densitometrically); and (c) bedding intake (a rodent indirect marker of nausea). Animals from sets 1 and 3 were used to evaluate gastric dysmotility ex vivo at 2 and 4hours after administration, respectively. Loperamide significantly induced antinociception, hypothermia, and hypolocomotion (but not catalepsy) at high doses and dose-dependently reduced gastrointestinal motor function, with the intestine exhibiting higher sensitivity than the stomach. Whereas bedding intake occurred early and transiently, gastric dysmotility was much more persistent. Our results suggest that loperamide-induced nausea and gastric dysmotility might be temporally dissociated.

Sa1192 – Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Electrical Acustimulation on Gastric Dysmotility in Patients with Gastroesophageal Reflux Disease

Sa1192 – Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Electrical Acustimulation on Gastric Dysmotility in Patients with Gastroesophageal Reflux Disease

Gastrointestinal Dysmotility and the Implications for Respiratory Disease

Gastroesophageal reflux disease (GERD) is frequently implicated as a cause for respiratory disease. However, there is growing evidence that upper gastrointestinal dysmotility may play a significantly larger role in genesis of respiratory symptoms and development of underlying pulmonary pathology. This paper will discuss the differential diagnosis for esophageal and gastric dysmotility in aerodigestive patients and will review the key diagnostic and therapeutic interventions for this dysmotility. Previous studies have shown an association between GERD and pulmonary pathology in children with aerodigestive disorders. Recent publications have demonstrated the presence of esophageal and gastric dysfunction, using fluoroscopic and nuclear medicine studies, in aerodigestive patients who commonly present to pulmonary and otolaryngology clinics. High-resolution impedance manometry (HRIM) has revolutionized our understanding of esophageal dysmotility and its role in pathogenesis of aspiration and esophageal dysfunction and subsequent respiratory compromise. Esophageal and gastric dysmotility have a profound effect on development of respiratory symptoms and pulmonary sequalae in aerodigestive patients. However, our understanding of the pathophysiology is in its infancy. Prospective studies in are needed to address key clinical questions such as: What degree of dysmotility initiates respiratory compromise? What diagnostic tests and therapeutic options best predict aerodigestive outcomes?

Prokinetic effects of spinal cord stimulation and its autonomic mechanisms in dogs.

Spinal cord stimulation (SCS) is widely used to treat chronic pain by inhibiting sympathetic activity; however, it is unknown whether it exerts a prokinetic effect on gastric motility. Our aim was to explore effects and possible mechanisms of SCS on glucagon-induced gastric dysmotility and dysrhythmia. Seven female dogs with electrodes chronically placed on the dorsal column of the spinal cord between T10 and T12 segments were studied in 2 randomized sessions (glucagon+sham-SCS, glucagon+SCS). SCS at T10 using a set of optimized stimulation parameters was performed for 30minute immediately after glucagon injection. The antral manometry, electrogastrogram, and electrocardiogram were recorded to assess gastric contractions, gastric slow waves (GSW), and autonomic functions, respectively. (a) Compared to baseline, glucagon decreased antral motility index (MI) (6315±565 vs 3243±775, P<0.001), reduced the percentage of normal GSW (89±3% vs 58±3%, P<0.01), and increased sympathetic activity (0.25±0 0.06 vs 0.60±0.07, P<0.01). (b) The sympathetic activity was negatively correlated with antral MI (r=-0.558; P<0.01) and the percentage of gastric normal slow wave (r=-0.616; P<0.01). (c) SCS prevented the glucagon-induced impairment in antral hypomotility (MI: 5770±927 vs 5521±1238, P>0.05) and GSW abnormalities (% of normal waves: 84±4% vs 79±6%, P>0.05) and sympathetic activity (0.27±0.03 vs 0.33±0.07, P>0.05). Spinal cord stimulation dramatically improves glucagon-induced impairment in gastric contractions and slow waves by inhibiting sympathetic activity.