Gastric Pacing Research Articles

Roles of Interstitial Cells of Cajal in Intestinal Transit and Exogenous Electrical Pacing

The aims of this study were to investigate the role of interstitial cells of Cajal (ICCs) on small intestinal transit and its responses to exogenous pacing in W/W(v) mice. Eleven W/W(v) mice and their controls implanted with four pairs of gastrointestinal electrodes were used for testing the entrainment of slow waves. Another 20 W/W(v) mice and their controls equipped with a duodenal catheter and one pair of intestinal electrodes were used to test small intestinal transit represented by the geometric center (GC). Results were as follows. (1) The effect of pacing on slow wave frequency was sustained only in controls, and not in W/W(v) mice. (2) Both gastric and intestinal slow waves were completely entrained in controls and W/W(v) mice. Higher energy was required for pacing the stomach than the small intestine. (3) There was no significant difference in small intestinal transit between the controls and the W/W(v) mice (GC: 5.4 vs. 5.5). (4) Pacing showed no effects on small intestinal transit in either wild-type (GC: 5.4 vs. 5.6) or W/W(v) mice (GC: 5.5 vs. 5.7). We conclude that myenteric ICCs may not play an important role in the regulation of small intestinal transit in conscious mice. Gastric and intestinal pacing can be achieved without ICCs.

Intragastric Stimulation is Ineffective after Failed Adjustable Gastric Banding

Gastric pacing has gained popularity as an effective and safe minimally invasive procedure to treat morbid obesity. This study evaluates the outcome of gastric pacing as a bariatric re-do procedure in patients who developed failure after adjustable gastric banding (AGB) due to band migration. 8 patients were enrolled in this analysis. After implantation of an AGB, they had developed band failure due to band migration. The implantable gastric stimulator (IGS) was implanted laparoscopically as a second-line operation after gastroscopic removal of the band. Median time (range) from AGB complication to implantation of the IGS was 42 (10.3-50.3) months. During that time, all 8 patients had regained significant weight. All IGS devices could be implanted laparoscopically, without intra- or perioperative complications. The minimal body weight following IGS implantation was reached after 5 (0-12) months. The median observation time was 23 (11.3-27.5) months. 1 year after IGS implantation (n=7), median weight was 116 (98-165) kg, equivalent to a median BMI of 41.1 (36.055.8) kg/m(2), which is not statistically different to preoperative values and therefore prompted us to stop our ongoing trial. In all but 2 patients, the IGS device was explanted. During the same procedure, patients underwent a gastric sleeve resection (n=4) or a Roux-en-Y gastric bypass (n=2). The implantation of an IGS was an ineffective second-line operation after AGB migration.

Pre-Pyloric Neural Electrical Stimulation Produces Cholinergically-Mediated Reverse Peristalsis in the Acute Canine Model of Microprocessor-Invoked Gastric Motility for the Treatment of Obesity

Gastric Electrical Stimulation (GES) has been suggested as a new tool for the treatment of obesity. Among the known methods for GES, only Neural Gastric Electrical Stimulation (NGES) provides direct control of contractility without utilizing the spontaneously existing gastric electrical activity as an intermediary. However, only one of the established GES techniques, gastric pacing, has been described to produce retrograde peristalsis for delaying gastric emptying. The aim of this study was to explore the possibility of producing retrograde peristalsis using either single electrode set or dual electrode set NGES. 8 anesthetized dogs underwent laparotomy and implantation of 2 circumferential electrode sets approximately 3 cm and 7 cm proximal to the pylorus, respectively. Single-set and dual-set NGES sessions were repeatedly administered using a custom-designed implantable neurostimulator. Gastric motility patterns were captured using 3 force transducers implanted on the anterior gastric wall along the gastric axis. Motility indices and velocities were employed to quantify the produced contractile patterns. Both single-set and dual-set NGES produced circumferential lumen-occluding contractions in the vicinity of the electrode sets. The invoked contractions propagated proximally in a retrograde fashion. The propagation scope was different depending on the number of electrode sets used. Different velocities of the invoked retrograde contractions associated with single- and dual-set NGES were observed and quantified. Contractility patterns reflected by the normalized motility indices were very similar regardless of the electrode stimulation technique. Pre-pyloric NGES can produce controlled retrograde peristalsis and serve as another avenue for the treatment of obesity.

Food intake reduced by reverse gastric pacing in dogs

Food intake reduced by reverse gastric pacing in dogs

The Implantable Gastric Stimulator for Obesity

To evaluate the efficacy of a gastric stimulation procedure for the treatment of morbid obesity. All implantable gastric stimulator systems were implanted in a laparoscopic procedure. We focused on the results of the LOSS (Laparoscopic Obesity Stimulation Survey) study, which was a multicenter European survey of 16 hospitals. To date, 91 patients have undergone implantable gastric stimulator implantation in the LOSS study. The patient population was comprised of 62 (68%) women and 29 (32%) men. The mean age was 41 years, mean weight was 116kg, and mean body mass index was 41 kg/m(2). All surgical procedures were successfully completed. There were no deaths, and no severe peri- or postoperative complications. The mean excess weight loss (EWL) was 20% at 12 months after surgery and about 25% at 2 years after implantation. Baroscreen-selected patients achieved a 31.4% EWL, which was significantly different to the EWL of those patients who were not selected by this screening (15% EWL) [p < 0.01]. Gastric pacing is a promising, minimally invasive, safe, and effective surgical method that results in very little impairment of the patient. Patient selection for gastric stimulation therapy seems to be an important determinant of treatment outcome.

Reverse gastric pacing reduces food intake without inducing symptoms in dogs

Objective. To investigate the therapeutic potential of reverse gastric pacing (RGP) for obesity by studying the effects of RGP on food intake and symptoms in dogs. Material and methods. The study was performed in 9 dogs in 3 sessions (control, strong RGP and moderate RGP). Gastric myoelectrical activity and food intake were measured in each session. RGP was performed using serosal electrodes implanted in the distal stomach at the physiological frequency of the intrinsic gastric myoelectrical activity with a pulse width of 550–950 ms. The amplitude of the stimulus was set at a level maximally tolerable by the animals in the strong RGP session and 50% of the maximum level in the moderate session. Results. 1) Compared with the control, strong RGP (p<0.001) and moderate RGP (p<0.01) significantly reduced the amount of food intake by 62.9% and 31.7%, respectively (p<0.05, ANOVA). 2) Whereas strong RGP induced significant symptoms, moderate RGP did not induce any significant symptoms in comparison with the control session. 3) The regularity and coupling of gastric myoelectrical activity were significantly impaired with both strong RGP and moderate RGP in the fasting state. Conclusions. RGP impairs intrinsic gastric myoelectrical activity and substantially and acutely reduces food intake. The reduced food intake and freedom from symptoms resulting from moderate RGP are indicative of the therapeutic potential of RGP in obesity.

Retrograde Gastric Pacing Reduces Food Intake and Delays Gastric Emptying in Humans: A Potential Therapy for Obesity?

Obesity is one of the most prevalent health problems in the world with a lack of satisfactory therapies and gastric electrical stimulation has recently been proposed for the treatment of obesity. The aim of this study was to investigate the effects of retrograde gastric pacing (RGP) on food and water intake, and gastric emptying in humans. RGP with a tachygastrial frequency of 9 cycles/min was performed via a pair of submucosal gastric electrodes implanted 5 cm above the pylorus in 12 subjects. The water load test, food intake test and scintigraphic gastric emptying test were performed to assess the efficacy of RGP. RGP resulted in a 13% reduction in the consumption of water, a 16% reduction in food intake and a 15% increase in gastric retention of a solid meal. No significant symptoms were recorded with RGP using the parameters used for the water-load, food intake and scintigraphic gastric emptying tests. Acute RGP at a tachygastrial frequency results in a significant reduction of water and food intake and a delay in gastric emptying without inducing any unacceptable symptoms. It is worthy to explore its therapeutic potential for obesity.

American Gastroenterological Association medical position statement: Diagnosis and treatment of gastroparesis

This document presents the official recommendations of the American Gastroenterological Association (AGA) on Diagnosis and Treatment of Gastroparesis. It was approved by the Clinical Practice Committee on May 16, 2004, and by the AGA Governing Board on September 23, 2004.

Gastric Pacing is Not Enough: Additional Measures for an Effective Obesity Treatment Program

Gastric Pacing is Not Enough: Additional Measures for an Effective Obesity Treatment Program

Gastric stimulation: a new paradigm for management of morbid obesity.

The introduction of gastric pacing into bariatric surgery heralds a new paradigm and represents a novel approach to the management of the disease of morbid obesity. This innovation extends today's standard concepts of inducing weight loss by gastric restriction and intestinal malabsorption to satiety induction by physiologic or biochemical mechanisms elicited by repetitive electronic gastric stimulation. To date, gastric pacing has been demonstrated to reduce appetite, increase satiety, inhibit gastric motility, and directly affect central nervous system mechanisms and hormones related to satiety and/or appetite. Current clinical studies of gastric pacing with the Transneuronix Implantable Gastric Stimulator (IGS®) system have shown the laparoscopic placement of bipolar electrode leads into the wall of the stomach, and the subcutaneous implantation of a battery-powered pacer, to be extremely safe and relatively easy. Further, this form of bariatric therapy allows for percutaneous adjustment of the pacer and its effect on the gastric wall, with the opportunity to temporarily discontinue therapy. The weight loss outcomes of the clinical trials with this system to date have been mixed and have clearly demonstrated the need for preoperative patient selection. The fact that only certain well-

Gastric pacing is not enough: additional measures for an effective obesity treatment program.

Obesity has long been considered a behavioral disorder. Recent breakthroughs in our understanding of body weight regulation, however, have shown that once adipose tissue accumulates, a system of overlapping neuroendocrine systems actively resists weight loss. This counter-regulatory mechanism, which has evolved as protection against starvation, causes changes in appetite and metabolism that limit the amount of weight lost with every obesity intervention, including surgery. Future therapies for obesity will focus on neutralizing the counter-regulatory mechanisms in a coordinated manner, making greater weight losses possible. At this point, gastric stimulation appears to play a role in suppressing the compensatory mechanisms of the gut. Thus, gastric stimulation should work best when combined with other treatments such as diet, exercise, and behavioral change.

Long-term follow-up of gastric stimulation for obesity: the Mestre 8-year experience.

10 years experience with gastric stimulation demonstrates promise, in particular because weight loss is achieved and maintained without drugs or side-effects. We report on a total of 65 patients who have received an Implantable Gastric Stimulator (IGS(R)) since 1995. 65 patients have received an IGS and were monitored for weight loss as well as co-morbidities. Gastroesophageal Reflux Disease (GERD) was assessed by endoscopy and symptoms were evaluated. An acute Holter study was performed on 4 patients pre-implant, post-implant, and post-activation of the IGS. Oral glucose tolerance test (OGTT) using a 76-g bolus of oral dextrose was done before device implantation and after-activation. Gastric emptying was tested on 19 of the patients using Tc99, both pre-implant and 6 months post-implant. Resting Energy Expenditure (REE) was studied in 15 patients using indirect calorimetry at 3 different points in time: pre-activation, 6 months post-implant, and 12 months post-implant. Blood pressure was measured using an electronic wrist device to overcome potential artifacts due to arm fat. IGS patients lost significant weight with no side-effects and experienced significant and rapid improvements in blood pressure. Almost all of the GERD patients reported symptomatic relief during gastric pacing. OGTT demonstrated improved response to insulin at 7 months post-stimulation. The gastric emptying and REE tests were less conclusive, to a great extent because of the small sub-population of patients. While the exact mechanisms of gastric stimulation remain incompletely understood, it appears that the implantation of an IGS is associated with weight loss, an improvement (decrease) in blood pressure in hypertensive patients, and a reduction or elimination of symptoms in those who had GERD. This promising weight loss therapy warrants further study, in particular because of its intriguing results with co-morbidities.

Effects of surface gastric pacing on gastric myoelectrical activity and plasma motilin in a canine model of gastric motility disorders

To investigate the effects of surface gastric pacing on gastric myoelectrical activity and plasma motilin concentration in a canine model of gastric motility disorders. Ten healthy mongrel dogs were divided into two groups: an experimental group of six dogs and control group of four dogs. The model of gastric motility disorders was established in the experimental group with truncal vagotomy combined with injection of glucagon. Gastric serosal myoelectrical activity was recorded with a four-channel computer analysis device. Plasma motilin concentration was measured with a radioimmunoassay (RIA) kit. Surface gastric pacing at 1.1-1.2-fold the intrinsic slow-wave frequency superimposed with a series of high frequency pulses (10-30 Hz) was performed for 45 min daily for 1 month in the conscious dogs. The basic electrical rhythm (BER) amplitude (2.32 +/- 0.35 mV) and propagation velocity (4.06 +/- 0.40 cm/s) of the dogs with bilateral truncal vagotomy in the fed state decreased more significantly than those of the controls (4.25 +/- 0.12 mV, 6.92 +/- 0.24 cm/s) (P < 0.03). After long-term surface gastric pacing, the BER amplitude (3.97 +/- 0.19 mV) and propagation velocity (5.57 +/- 0.48 cm/s) was increased significantly compared with before pacing (P < 0.05). Postprandial gastric dysrhythmias were provoked by large doses of glucagon; the percentage of regular slow waves of the dogs with vagotomy was markedly reduced from 67.4 +/- 6.2% at baseline to 10.0 +/- 6.7% (P < 0.001), and that of the control was also decreased from 87.1 +/- 6.9% to 35.0 +/- 11.0% (P < 0.01), but the entrainment of gastric slow waves was 100% by means of gastric pacing at optimal parameters. There was a significant increase in the plasma concentration of motilin at the phase III of the interdigestive myoelectrical complex (IMC III) in the dogs with bilateral truncal vagotomy (baseline vs vagotomy, 184.29 +/- 9.81 pg/mL vs 242.09 +/- 17.22 pg/mL; P< 0.01). However, the plasma motilin concentration (212.55 +/- 11.20 pg/mL; P < 0.02) was decreased significantly after long-term gastric pacing. Before gastric pacing the plasma motilin concentration showed an equally negative correlation with the BER amplitude, and propagation velocity in the dogs with vagotomy in the fed state (r = -0.473, r = -0.807, P < 0.04), but after long-term gastric pacing, the plasma motilin concentration showed an equally positive correlation with the BER amplitude and propagation velocity (r = 0.523, r = 0.896, P < 0.02). Surface gastric pacing with optimal pacing parameters is able to entrain completely propagated slow waves, improve the parameters of gastric myoelectrical activity and normalize gastric dysrhythmias induced by a pharmacological agent. Surface gastric pacing might be useful in the treatment of gastric dysrhythmia. The gastric myoelectrical activity correlated well with the plasma motilin concentration before and after pacing, which suggests that motilin could modulate the effect of gastric pacing through alteration of the gastric myoelectrical parameters.

Gastric pacing for severe gastroparesis in a heart–lung transplant recipient

Gastroparesis is a serious complication of lung and heart–lung transplantation that can lead to malnutrition, gastroesophageal reflux, aspiration pneumonia and deteriorating lung function. Some patients with severe gastroparesis have symptoms that are refractory to dietary modifications and gastric promotility agents and require surgery. We describe the successful use of gastric pacing for the management of intractable gastroparesis, malnutrition and recurrent aspiration in a heart–lung allograft recipient. Lung transplant recipients with severe gastroparesis may benefit from gastric pacing.

Effects of gastric pacing on gastric emptying and plasma motilin.

To investigate the effects of gastric pacing on gastric emptying and plasma motilin level in a canine model of gastric motility disorders and the correlation between gastric emptying and plasma motilin level. Ten healthy Mongrel dogs were divided into: experimental group of six dogs and control group of four dogs. A model of gastric motility disorders was established in the experimental group undergone truncal vagotomy combined with injection of glucagon. Gastric half-emptying time (GEt(1/2)) was monitored with single photon emission computerized tomography (SPECT), and the half-solid test meal was labeled with an isotope-(99m)Tc sulfur colloid. Plasma motilin concentration was measured with radioimmunoassay (RIA) kit. Surface gastric pacing at 1.1-1.2 times the intrinsic slow-wave frequency and a superimposed series of high frequency pulses (10-30 Hz) was performed for 45 min daily for a month in conscious dogs. After surgery, GEt(1/2) in dogs undergone truncal vagotomy was increased significantly from 56.35+/-2.99 min to 79.42+/-1.91 min (P<0.001), but surface gastric pacing markedly accelerated gastric emptying and significantly decreased GEt(1/2) to 64.94+/-1.75 min (P<0.001) in animals undergone vagotomy. There was a significant increase of plasma level of motilin at the phase of IMCIII (interdigestive myoelectrical complex, IMCIII) in the dogs undergone bilateral truncal vagotomy (baseline vs vagotomy, 184.29+/-9.81 pg/ml vs 242.09+/-17.22 pg/ml; P<0.01). But plasma motilin concentration (212.55+/-11.20 pg/ml; P<0.02) was decreased significantly after a long-term treatment with gastric pacing. Before gastric pacing, GEt(1/2) and plasma motilin concentration of the dogs undergone vagotomy showed a positive correlation (r=0.867, P<0.01), but after a long-term gastric pacing, GEt(1/2) and motilin level showed a negative correlation (r=-0.733, P<0.04). Surface gastric pacing with optimal pacing parameters can improve gastric emptying parameters and significantly accelerate gastric emptying and can resume or alter motor function in a canine model of motility disorders. Gastric emptying is correlated well with plasma motilin level before and after pacing, which suggests that motilin can modulate the mechanism of gastric pacing by altering gastric motility.

Gastric Pacing: A New Modality for the Treatment of Morbid Obesity

Gastric Pacing: A New Modality for the Treatment of Morbid Obesity

Gastric pacing for morbid obesity: plasma levels of gastrointestinal peptides and leptin.

A gastric pacemaker has been developed to treat morbid obesity. Patients experience increased satiety, the ability to reduce food intake, and a resultant weight loss. However, the mechanism behind the changed eating behavior in paced patients is still under investigation. This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m2) treated with gastric pacing. The peripheral blood levels of satiety signals of cholecystokinin (CCK), somatostatin, glucagon-like peptide-1 (GLP-1), and leptin were studied 1 month before gastric pacer implantation, 1 month after implantation, and 6 months after activation of electrical stimulation. Blood samples were drawn 12 hours after fasting and in response to a hypocaloric meal (270 kcal). Patients were followed monthly for vital signs and weight level. Gastric pacing resulted in a significant weight loss of a mean of 10.4 kg (4.4 BMI units). No negative side effects or complications were observed during the treatment. After activation of the pacemaker, meal-related response of CCK and somatostatin and basal levels of GLP-1 and leptin were significantly reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01). Gastric pacing is a novel and promising therapy for morbid obesity. Activation of the gastric pacer was associated with a decrease in plasma levels of CCK, somatostatin, GLP-1, and leptin. More studies are necessary to elucidate the correlations between satiety, weight loss, and digestive neuro-hormone changes.

The use of a gastric pacing system with data telemetry to develop a chronic pacing non anesthetized porcine model

The use of a gastric pacing system with data telemetry to develop a chronic pacing non anesthetized porcine model

Feasibility of gastric pacing using pulse trains and effects of duty cycles

Feasibility of gastric pacing using pulse trains and effects of duty cycles

Current concepts in diabetic gastroparesis.

Diabetic gastroparesis is a common and debilitating condition affecting millions of patients with diabetes mellitus worldwide. Although gastroparesis in diabetes has been known clinically for more than 50 years, treatment options remain very limited. Until recently, the scientific literature has offered few clues regarding the precise aetiology of gastric dysfunction in diabetes.Up to 50% of patients with diabetes may experience postprandial abdominal pain, nausea, vomiting and bloating secondary to gastric dysfunction. There is no clear association between length of disease and the onset of delayed gastric emptying. Gastroparesis affects both type 1 (insulin dependent) and type 2 (non- insulin dependent) forms of diabetes. Diagnosis requires identifying the proper symptom complex, while excluding other entities (peptic ulcer disease, rheumatological diseases, medication effects). The diagnosis of gastroparesis may be confirmed by demonstrating gastric emptying delay during a 4-hour scintigraphic study. Treatment options are limited and rely on dietary modifications, judicious use of available pharmacological agents, and occasionally surgical or endoscopic placement of gastrostomies or jejunostomies. Gastric pacing offers promise for patients with medically refractory gastroparesis but awaits further investigation. Current pharmacological agents for treating gastroparesis include metoclopramide, erythromycin, cisapride (only available via a company-sponsored programme) and domperidone (not US FDA approved). All of these drugs act as promotility agents that increase the number or the intensity of gastric contractions. These medications are not uniformly effective and all have adverse effects that limit their use. Cisapride has been removed from the open market as a result of over 200 reported cases of cardiac toxicity attributed to its use. Unfortunately, there is a paucity of clinical studies that clearly define the efficacy of these agents in diabetic gastroparesis and there are no studies that compare these drugs to each other. The molecular pathophysiology of diabetic gastroparesis is unknown, limiting the development of rational therapies. New studies, primarily in animals, point to a defect in the enteric nervous system as a major molecular cause of abnormal gastric motility in diabetes. This defect is characterised by a loss of nitric oxide signals from nerves to muscles in the gut resulting in delayed gastric emptying. Novel therapies designed to augment nitric oxide signalling are being studied.