Effects Of Gastric Electrical Stimulation Research Articles

The Effect of Gastric Electrical Stimulation on Small Bowel Motility in Patients With Gastroparesis and Concomitant Pancreatic and Small Bowel Dysfunction: From Animal Model to Human Application

Patients with gastroparesis often have biliary/pancreatic and small bowel symptoms but the effects of gastric electrical stimulation on small bowel electrical activity of the mid-gut have not been studied. Animal model aim: Establish gastric and upper small bowel/biliary slow wave activity relationships with electrical stimulation. Human study aim: Demonstrate improvement in symptoms associated with proximal small bowel dysmotility in gastric stimulated patients. Animal model: In vivo evoked responses of duodenal and Sphincter of Oddi measures recorded during gastric electrical stimulation in a nonsurvival swine model (N = 3). High-resolution electrical slow wave mapping of frequency, amplitude, and their ratio, for duodenal and Sphincter of Oddi electrical activity were recorded. Human study: Patients (N = 8) underwent temporary gastric stimulation with small bowel electrodes. Subjective and objective data was collected before and after temporary gastric stimulation. Symptom scores, gastric emptying times, and mucosal electrograms via low-resolution mapping were recorded. Animal gastric stimulation resulted in some changes in electrical activity parameters, especially with the highest energies delivered but the changes were not statistically significant. Human study revealed improvement in symptom and illness severity scores, and changes in small bowel mucosal slow wave activity. Gastric electrical stimulation in an animal model seems to show nonsignificant effects small bowel slow wave activity and myoelectric signaling, suggesting the existence of intrinsic neural connections. Human data shows more significance, with possible potential for therapeutic use of electrical stimulation in patients with gastroparesis and pancreato-biliary and small bowel symptoms of the mid-gut. This study was limited by the nonsurvival pig model, small sample size, and open label human study.

296 Effectiveness of Gastric Electrical Stimulation in Gastroparesis: Results From a Large Prospectively Collected Database of a National Gastroparesis Registry

296 Effectiveness of Gastric Electrical Stimulation in Gastroparesis: Results From a Large Prospectively Collected Database of a National Gastroparesis Registry

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs

The aims of this study were to investigate the effect of gastric electrical stimulation (GES) with different parameters on emesis induced by apomorphine, and possible center mechanisms by brain functional magnetic resonance imaging (fMRI). Six dogs implanted with electrodes on gastric serosa were used in this study. Part 1: Apomorphine was injected in the control session and GES sessions. GESs with different parameters were applied in GES session. Gastric slow waves and emesis and behaviors suggestive of nausea were recorded in each session. Part 2: Each dog was anesthetized and given GESs with different parameters or sham stimulation for 15 min after baseline (5 min), respectively. The location of cerebral activation induced by GES was investigated by fMRI. Apomorphine induced emesis and behaviors suggestive of nausea, and gastric dysrhythmia. The emesis frequency in control session was 5.5 ± 0.99, and symptoms score was 22.17 ± 1.01. GES with short pulse and long pulse could not improve emesis and symptoms induced by apomorphine. The emesis frequency (4.5 ± 0.76 in short pulse and 6.33 ± 1.05 in long pulse) and symptoms scores had no significant difference compared to control session (each p > 0.05). GES with trains of short pulse reduced emesis time frequency (3.83 ± 0.7, p = 0.042 vs control) and symptoms score (p = 0.037 vs control) obviously. Brain fMRI showed that GES with short pulse and long pulse activated brain stem region, and trains of short pulse made amygdala and occipital lobe activation. Apomorphine induced emesis and gastric dysrhythmia. GES with trains of short pulses relieves emetic responses through activation of amygdala region.

The Acute Effects of a New Type of Implantable Gastric Electrical Stimulators Featuring Varied Pulse Widths on Beagle Dogs’ Food Intake and Gastric Accommodation

To improve the therapeutic effects of gastric electrical stimulation (GES) for obesity, an animal experiment was conducted using a new type of stimulators. Proper parameters of GES were selected, and the impacts of GES on the food intake and gastric accommodation of canines were observed. Eight beagle dogs were operated on, and GES was performed on them. Firstly, GES was performed to determine the right parameters according to symptoms. Secondly, the so selected parameters were used in a 3-day GES procedure, during which process food intake, body weight, and symptoms were recorded. Thirdly, the gastric capacities before and after GES with different pulse widths were measured by means of a barostat. The selected parameters varied for each dog, with the pulse widths ranging from 0.3 to 6ms. The food consumption after GES dropped significantly as compared with the amount observed in the sham stimulation. Tolerance to stimulation could be observed during GES. The post-GES gastric fundus capacity increased evidently in comparison with the capacity before GES, suggesting significant distention as compared with sham stimulation. Given an increment of 2ms in the pulse width twice, the gastric capacity continued to distend each time. GES featuring pulse trains with wider and individualized pulse widths could inhibit food consumption of dogs. The stimulation parameters should be selected individually and adjusted periodically. GES of this mode could also increase the fasting gastric capacity with certain dose-related effects. The new type of stimulators may be more suitable for the treatment of human obesity than traditional stimulators.

Sa2063 The Role of Nerve Growth Factor in the Ameliorating Effect of Gastric Electrical Stimulation on Visceral Hypersensitivity

Sa2063 The Role of Nerve Growth Factor in the Ameliorating Effect of Gastric Electrical Stimulation on Visceral Hypersensitivity

Mo2058 Differential Effect of Gastric Electrical Stimulation on Heart Rate Variability in Patients With Diabetic and Idiopathic Gastroparesis

Mo2058 Differential Effect of Gastric Electrical Stimulation on Heart Rate Variability in Patients With Diabetic and Idiopathic Gastroparesis

Improvement of quality of life and symptoms after gastric electrical stimulation in children with functional dyspepsia

Our objective is to evaluate the effect of gastric electrical stimulation (GES) on symptoms and quality of life for pediatric patients with functional dyspepsia (FD). Twenty-four patients (16 female, median 15years) were treated with GES for FD after a median of 24months of symptoms (3months-14years). At baseline, 46% required tube feeds and 25% parenteral nutrition. Sixty percent had gastroparesis. The PedsQL GI Module (PedsQL) was completed for 18/24 both pre-/post-GES after a median of 8months. Patients also completed the Symptom Monitor Worksheet (SMW) pre-/post-GES after a median of 6months. Pre-/post-GES global health was also assessed. Significant improvements were seen in multiple areas of the PedsQL, including stomach pain/upset, food/drink limits, heartburn/reflux, gas/bloating, patient worry, medication tolerance, and constipation (P<0.05). A decrease was found in combined symptom severity/frequency based on SMW (P<0.01). Improvements were made in all categories, including vomiting, nausea, early satiety, bloating, fullness, epigastric pain, and burning (P<0.01). Improvements in PedsQL/SMW scores remained when analysis was limited to normal or delayed gastric emptying (P<0.05, P<0.05). Thirteen percent needed tube feeds and 13% parenteral nutrition after GES. Sixty-five percent reported that their health was much improved after GES vs 15% the same or worse. Five patients experienced complications, primarily mild abdominal discomfort. In the largest series to date of pediatric patients who have undergone GES for FD, we found significant improvements in upper gastrointestinal symptoms, quality of life, and perception of global health. Patients were less dependent on tube feeding or parenteral nutrition.

Treatment of high‐frequency gastric electrical stimulation for gastroparesis

The aim of this study was to assess the effects of gastric electrical stimulation (GES) on symptoms and gastric emptying in patients with gastroparesis, and the effects of GES on the three subgroups of gastroparesis. A literature search of clinical trials using high-frequency GES to treat patients with gastroparesis from January 1995 to January 2011 was performed. Data on the total symptom severity score (TSS), nausea severity score, vomiting severity score, and gastric emptying were extracted and analyzed. The statistic effect index was weighted mean differences. Ten studies (n = 601) were included in this study. In the comparison to baseline, there was significant improvement of symptoms and gastric emptying (P < 0.00001). It was noted that GES significantly improved both TSS (P < 0.00001) and gastric retention at 2 h (P = 0.003) and 4 h (P < 0.0001) in patients with diabetic gastroparesis (DG), while gastric retention at 2 h (P = 0.18) in idiopathic gastroparesis (IG) patients, and gastric retention at 4 h (P = 0.23) in postsurgical gastroparesis (PSG) patients, did not reach significance. Based on this meta-analysis, the substantial and significant improvement of symptoms and gastric emptying, and the good safety we observed, indicate that high-frequency GES is an effective and safe method for treating refractory gastroparesis. DG patients seem the most responsive to GES, both subjectively and objectively, while the IG and PSG subgroups are less responsive and need further research.

Mucosal Nerve Fiber Density Studies May Yield Insights into the Effects of Gastric Electrical Stimulation on Treatment Outcomes

Purpose: Debilitating nausea and vomiting frequently lead to reduced activity and quality of life in patients with gastroparesis (GP). Mucosal nerve fiber (MNF) density studies may help in characterizing Gp symptoms. Methods: Gastric mucosal tissues from 5 Gp patients (mean age 53.5 yrs; 80% Caucasian, 80% female; 1 diabetic, 2 idiopathic, 2 postsurgical Gp) and 3 age-matched controls were compared. For Gp patients, full thickness stomach biopsies, obtained at permanent stimulator implantation, were processed, and samples fixed in Zamboni's solution. Superficial MNF length density (μm/μm3) was evaluated using PGP 9.5 immunostained sections, imaged by confocal microscopy and quantified with AutoNeuron®. Results were analyzed by linear regression models using STATA 11. Gastroparesis symptom were assessed using a patient-reported, Likert-scale tool (0 to 4, none to severe). Clinical histories were studied to record duration of disease. Results: MNF density was reduced in GP, at 0.0018, compared to age-matched controls, at 0.0024 (p = 0.02). Significant associations were seen between MNF density and baseline Gp symptoms of bloating anorexia, abdominal pain, and total symptoms score (See Table). A significant association was also observed between duration of disease and reduction in MNF densities, at 6.03 [2.42, 9.64] p = 0.013.Table: Table. Associations between mucosal nerve fiber density and gastroparesis symptomsConclusion: The associations between reduced MNF density and both Gp duration and symptom severity are important findings that may improve our understanding of the natural progression of gastroparesis. The relationship between MNF density and symptom severity in particular should be explored to improve treatment and outcomes for patients with gastroparesis. Disclosure: Dr Thomas L Abell is licensor, instructor and consultyant for Medtronic Inc.

Short pulse gastric electrical stimulation for cisplatin‐induced emesis in dogs

In a previous study, we investigated the ameliorating effect of gastric electrical stimulation (GES) with a single set of parameters on emesis and behaviors suggestive of nausea induced by cisplatin in dogs. The aim of this study was to investigate the effects of GES with different parameters on cisplatin-induced emesis in dogs. Seven dogs implanted with gastric serosal electrodes were studied in six randomized sessions: one control session with cisplatin (2 mg kg(-1)) and five sessions with cisplatin plus GES of different parameters: GES-A: 14 Hz, 5 mA, 0.3 ms, 0.1 s on and 5 s off; GES-B: increased frequency and on-time; GES-C: increased frequency; GES-D: increased frequency and pulse width; and GES-E: increased frequency and amplitude. Gastric slow waves and emetic responses were recorded in each session. (i) Cisplatin induced emetic responses and gastric dysrhythmia. The peak time of the emetic response was during the fourth hour after cisplatin. (ii) GES with appropriate parameters reduced cisplatin-induced emesis. The number of vomiting times during the 6 h after cisplatin was 7.0 ± 1.4 in the control, 4.7 ± 1.2 with GES-A (P = 0.179), 4.2 ± 1.2 with GES-B (P = 0.109), 7.0 ± 0.8 with GES-C (P = 0.928), 2.1 ± 0.3 with GES-D (P = 0.005) and 4.7 ± 1.5 with GES-E (P = 0.129). However, none of the GES parameters could improve gastric dysrhythmia. Gastric electrical stimulation with appropriate parameters reduces cisplatin-induced emetic responses and behaviors suggestive of nausea in dogs. Among the tested parameters, GES with increased pulse width seems to produce better relief of cisplatin-induced emesis.

A slow caloric satiety drinking test in patients with temporary and permanent gastric electrical stimulation

Improvement of gastric accommodation has been proposed as a potential explanation for the positive effect of gastric electrical stimulation (GES) on nausea/vomiting. A drinking test has been suggested as a noninvasive measure of gastric accommodation capacity. Eight patients with therapy refractory nausea and vomiting and nonapproved diagnosis for GES (chronic intestinal pseudo-obstruction (CIP, n=1), functional dyspepsia (FD, n=3), postsurgical gastroparesis (PSGP, n=4) underwent temporary percutaneous GES for 10-14 days, randomized to stimulation ON or OFF, respectively. 19 patients [CIP (n=1), diabetic gastroparesis (n=5), FD (n=5), idiopathic gastroparesis (n=4), PSGP (n=4)] received permanent GES (Enterra, Medtronic) (follow-up at baseline, 6 and 12 months). At the end of each stimulation period a slow caloric satiety drinking test was performed (Nutridrink 1.5 kcal/ml, 15 ml/min). Healthy volunteers had higher drinking capacity compared to patients at baseline (1630 + or - 496 kcal vs. 887 + or - 412; P<0.001) and less composite symptom score (128 + or - 51 vs. 235 + or - 83; P<0.001). With temporary percutaneous GES, there was no significant change in drinking capacity during stimulation ON versus OFF (746 + or - 383 vs. 734 + or - 427 kcal) and symptom severity at the drinking test was unchanged. For patients having permanent GES there was no significant difference at 6 months (876 + or - 277 kcal) versus baseline, and no difference between symptomatic responders and nonresponders in change in drinking capacity (P=0.7). GES had no effect on proximal gastric function as evaluated by the slow caloric satiety drinking test. This seems to be the case for patients with approved as well as nonapproved indications for GES, and irrespective of the symptomatic response.

W1420 Effect of Gastric Electrical Stimulation on Intractable Nausea and Vomiting in Patients With Gastroparesis – Single Centre UK Study

W1420 Effect of Gastric Electrical Stimulation on Intractable Nausea and Vomiting in Patients With Gastroparesis – Single Centre UK Study

Cellular effects of gastric electrical stimulation on antral smooth muscle cells in rats

The cellular effects of gastric electrical stimulation (GES), which has recently been introduced as a potential therapy for the treatment of gastroparesis and obesity, were investigated in rat antrum smooth muscle cells (SMCs). Effects on cell membrane potentials of single electrical current pulses (pulse width from 0.1 ms to 200 ms) and 2-s pulse train stimuli with different pulse widths (0.1-4 ms), different frequencies (20-200 Hz), and different intensities were studied: 1) the stimulus amplitude had an exponential relationship to the pulse width from 2 ms to 200 ms, along with a rapidly rising strength-duration curve at pulse widths less than 5 ms, and a relatively flat curve at pulse widths greater than 50 ms; 2) when the pulse frequency was at 80 Hz or above, pulse train electrical stimulation, with a pulse width of 2 ms or above but not < or = 1 ms, was able to depolarize cell membrane potentials to above -30 mV and/or generate action potentials. Electrical stimulation with a single long pulse and a width of 50 ms or greater is effective in depolarizing cell membrane potentials of SMCs with low amplitude. Pulse train electrical stimulation with a pulse width of < or = 1 ms fails to generate action potentials in SMCs, whereas pulse train electrical stimulation with a pulse width of 2-4 ms and a sufficiently high pulse frequency is able to generate action potentials. These cellular findings may be useful in optimizing stimulation parameters of GES.

Mechanisms of symptomatic improvement after gastric electrical stimulation in gastroparetic patients

The aims were to investigate the effects of gastric electrical stimulation (GES) on autonomic function, gastric distention and tone, and central control mechanisms in gastroparetic patients. Ten gastroparetic patients refractory to standard medical therapy participated in this study and data were collected at baseline, within two weeks before surgery for implantation of GES system, and at follow-up sessions between 6 and 12 weeks after GES therapy was initiated. In each session, electrocardiogram, electrogastrogram (EGG) and gastric barostat measurements were conducted before and after a caloric liquid meal. Positron Emission Tomography (PET) brain scans were performed on a separate day. During GES therapy there was a significant increase in the discomfort threshold for mean pressure from 21 mmHg at baseline to 25 mmHg at follow-up, and for mean volume from 561 mL to 713 mL. A significant increase in the postprandial EGG power (amplitude) was observed between baseline and follow up. The sympathovagal balance was significantly decreased after GES therapy, indicating a significant increase in vagal activity. The cumulative PET data showed an increase in quantitative radioactive counts relative to the standardized data base in both the thalamic and caudate nuclei after chronic GES therapy. We conclude that our data suggest that the symptomatic improvement achieved by GES in gastroparesis is best explained by activation of vagal afferent pathways to influence CNS control mechanisms for nausea and vomiting accompanied by enhanced vagal efferent autonomic function and decreased gastric sensitivity to volume distention which enhances postprandial gastric accommodation.

Effects and Mechanisms of Electrical Stimulation of the Stomach, Duodenum, Ileum, and Colon on Gastric Tone in Dogs

Previous studies have shown that gastric tone is inhibited by the electrical stimulation of some parts of the gut. The aims of this study were to investigate the effects of gastric electrical stimulation (GES), duodenal electrical stimulation (DES), ileal electrical stimulation (IES), and colonic electrical stimulation (CES) on gastric tone and the possible mechanism of electrical stimulation on gastric tone. Experiments were performed to study: (1) the effects of the four stimulations (GES, DES, IES, CES) on gastric tone; (2) the role of the nitrergic pathway's involvement in the effect of IES on gastric tone. Each dog was implanted with one pair of gastric, duodenal, ileal, and colonic electrodes and a gastric cannula. A computerized barostat was used to assess gastric tone by measuring the gastric intra-balloon volume. We found that: (1) all methods of stimulation significantly inhibited gastric tone; (2) the percentage of increase in gastric volume was highest with CES and lowest with DES; however, there was no significant difference in the percentage of inhibition among the four stimulations; (3) the inhibitory effect of IES on gastric tone was abolished by intravenous nitric oxide synthase inhibitor. It was concluded that electrical stimulation of the stomach, intestine, or colon with long pulses has an inhibitory effect on gastric tone, and the most effective stimulation is CES. The inhibitory effect is not organ-specific and is unrelated to the distance between the stimulation site and the affected organ. The inhibitory effect of IES on gastric tone is mediated by the nitrergic pathway.

W1852 Effects of Gastric Electrical Stimulation On LES Pressure and TLESRs in Conscious Dogs

W1852 Effects of Gastric Electrical Stimulation On LES Pressure and TLESRs in Conscious Dogs

Inhibitory Effects of Gastrointestinal Electrical Stimulation on Rectal Tone are both Organ-Specific and Distance-Related in Dogs

A phenomenon of cross-talk has been noted that electrical stimulation of one part of the gut affects another part of the gut. This study was designed to investigate whether the effect of electrical stimulation of one part of the gut on another part of the gut was related to the organ or the distance between the stimulation site and the affected organ, and the mechanism of ileum electrical stimulation on rectal tone. This study was performed in 13 healthy dogs (16-28 kg) in the fasting state. Experiments were performed to study 1) effects of gastric electrical stimulation, duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation on rectal tone, and 2) the sympathetic and nitrergic pathways involved in the effects of ileum electrical stimulation on rectal tone. A computerized barostat was used to assess rectal tone. All methods of stimulations significantly inhibited rectal tone. Duodenal electrical stimulation was least effective in reducing rectal tone. The percentage of increase in rectal volume was distance-related with duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation but organ-specific with gastric electrical stimulation. The inhibitory effect of ileum electrical stimulation on rectal tone was abolished by N omega-nitro-L-arginine but not guanethidine. Electrical stimulation of the stomach, intestine, or colon with long pulses has an inhibitory effect on rectal tone. This inhibitory effect is organ-specific as well as associated with the distance between stimulation site and affected organs. The inhibitory effect of ileum electrical stimulation on rectal tone is mediated by the nitrergic but not sympathetic pathway.

Effects of Gastric Electrical Stimulation with Short Pulses and Long Pulses on Gastric Dysrhythmia and Signs Induced by Vasopressin in Dogs

This study was to investigate the effect of gastric electrical stimulation (GES) with short pulses, long pulses, short-pulse trains or long-pulse trains on gastric dysrhythmia and motion-sickness signs induced by vasopressin. Seven male beagle dogs implanted with four pairs of electrodes on gastric serosa were studied. The study was performed in six sessions in a randomized order. In session 1 or 2, either saline or vasopressin was infused without GES. In session 3, 4, 5 and 6, GES with short pulses, long pulses, trains of short pulses or trains of long pulses was performed before and during vasopressin infusion. Gastric slow waves and motion-sickness signs were recorded in each session. (1) Vasopressin induced gastric dysrhythmia and motion sickness-like signs (ANOVA, P < 0.001). (2) GES with short pulses or trains of short pulses was capable of preventing vasopressin-induced emetic response (P < 0.001), but did not normalize gastric dysrhythmia. (3) GES with long pulses or trains of long pulses was able to normalize gastric dysrhythmia induced by vasopressin (P < 0.001), but showed no effects on vasopressin-induced motion-sickness signs. GES with short pulses or trains of short pulses prevents vasopressin-induced emetic response with no improvement in gastric dysrhythmia. GES with long pulses or trains of long pulses normalizes gastric dysrhythmia induced by vasopressin with no effects on signs.

Effect of Acute Gastric Electrical Stimulation on the Systemic Release of Hormones and Plasma Glucose in Dogs

This study evaluated the effect of gastric electrical stimulation (GES) with various parameters on plasma concentrations of satiety-related peptides and glucose. GES was performed in nine healthy dogs via electrodes implanted in the middle of the lesser curvature. Four sessions were performed in each animal: control, stimulation with IGS (implantable gastric stimulation for obesity, 0.3 m sec), modified IGS (2 msec), and long pulses (300 msec). Blood samples were collected at 15 and 0 min before the meal and at 15, 30, and 60 min after the meal. GES was initiated 30 min before the first blood sample and maintained throughout collection. Plasma ghrelin, leptin, insulin and glucose were measured. The total AUCs of plasma ghrelin and leptin were not significantly affected by GES. The total AUC of plasma insulin was significantly lower with IGS and long pulse parameters (P < 0.05). The total AUC for plasma glucose was significantly lower in sessions with long pulses and modified IGS parameters (P < 0.05). We conclude that acute GES is able to change the release of some satiety-related peptides. Whether this is associated with the changed eating behavior and weight loss in obese patients needs further investigation.

Effects of gastric electrical stimulation on hippocampus gastric distension responsive neurons and the expression of motilin and neuronal nitric oxide synthase in rats

Effects of gastric electrical stimulation on hippocampus gastric distension responsive neurons and the expression of motilin and neuronal nitric oxide synthase in rats