Selection Of Parameters Of The Adjustable Gastric Electrical Stimulator And Its Effect On Beagle Dogs’ Gastric Accommodation,Gastric Motility And Appetite-regulating Hormones

Background and ObjectivePrevention of obesity and related diseases has become a pressing issue. The latest development abroad in gastric electrical stimulation as a treatment for obesity has presented a promising prospect. Notwithstanding the prospect that gastric electrical stimulation can become an effective, safe and micro invasive treatment for obesity, there are some problems with this technique:1) as the sensitivity to gastric electrical stimulation vary among patients, application of the same unvaried parameter on all patients will not produce across-the-board effect;2) currently all the stimulators available on the market offer only one mode of stimulation parameters and relatively narrow pulse width as well as fixed parameters, which tend to affect effect of the treatment.An ideal implantable GES (with wider pulse width、adjustable、remotely rechargeable) is still absent from the market. In collaboration with Institute of Microelectronics of Tsinghua University, we have developed a new type of adjustable gastric electrical stimulator. This stimulator has passed in vito verification and preliminary animal experiment, showing good safety and satisfactory stimulatory signals and energy.In this study, the new type of adjustable GES was applied to produce gastric electric stimulation on Beagle dogs. GES parameters were selected and individualized. Then GES was conducted to observe the impacts on Beagle Dogs’gastric accommodation, gastric motility and appetite-regulating hormones. The objective was to verify the effectivenes and safety of the new type of GES and further probe into the functions and mechanisms of GES.MethodTwelve healthy adult Beagle dog, comprising two males and ten females and ranging in weight from8-12kg, were used in the expriment. Laparotomy was performed and the electrodes and stimulator were implanted.Part I:An animal model of GES and gastrotomy was built. GES parameters were screened. The stimulatory mode is pulse train:40Hz,10mA,2s-on,3s-off periodic rectangular pulse, pulse width0.3ms-10ms. Gastric electrical stimulation with varies parameters was performed. The food intake and symptoms were observed and ideal parameters were selected accordingly.Part II:In this part, individualized stimulation parameters were used to observe the impacts of GES on the gastric accommodation of the beagle dogs. Self control and blank control were designed to test the gastric accommodation. During the process, the fasting gastric capacity and the gastric capacity after30minutes of GES were measured. Subsequently, the intensity of GES was increased twice and gastric capacities were recorded each time. The gastric capacity was measured again thirty minutes after injection of liquid nutrient into the stomach.Part III:In this part, individualized stimulation parameters were used to observe the impacts of GES on antral and pyloric contractions of the beagle dogs. Measurement of antral and pyloric contractions was conducted with self control and blank control. The contraction was promptly measured within ninety minutes after intake of solid food (including30minutes of baseline,30minutes of GES, and30minutes recovery stage).Party IV:The serum and the gastric tissues before and after GES were obtained and assayed using Radio Immunoreactive Assay (RIA) technique for appetite-regulating peptides (including ghrelin, GLP-1, obestatin, PYY, insulin, leptin and resistin). ResultsAltogether four dogs were used to establish an animal model and other eight dogs were successfully applied for the above-mentioned study, demonstrating good compliance.Part Ⅰ: This animal model could be used to perform GES and test gastric accommodation and antral pressure; GES could reduce food consumption of the dogs, without severe complications. The stimulatory parameters selected on each dog varied, with the pulse width ranging from0.3ms to6ms; when stimulated using the selected parameters, their symptom scores range0~2poins/15points, showing good tolerance. At the early stage, their food consumption dropped evidently from usual amount (280.38±118.16g vs.202.63±l12.67g, P=0.001), with a percentage of decrease in consumption being (28.95±11.48)%; at the later stage, their food consumption continued to decrease significantly from usual figures (280.38±118.16g vs.217.75±92.97g, P=0.002), with a percentage of decrease in consumption being (22.23±8.89)%.Part Ⅱ: The post-GES gastric fundus capacity increased evidently as compared with the capacity before GES (106.22±47.25ml vs.61.83±31.82ml, P=0.037) showing also a significant distention as compared with the fundus capacity after the sham stimulation (68.65±25.65ml, P=0.036). Given an increment of2ms in pulse width, the gastric capacity continued to distend to144.37±55.81ml, increased significantly compared with the gastric capacity before the increment of width (P=0.036); given further increment of2ms in width, the gastric capacity continued to demonstrate a tendency of distension (146.47±74.95ml), notwithstanding less substantial difference than that produced by the previous stimulation (P=0.929).Part III: During the course of stimulation the antral contraction pressure (48.96±14.85mmHg) was significantly higher than both the antral pressure before the stimulation (30.64±12.70mmHg) and the antral pressure in the sham stimulation (20.51±10.87mmHg). On the other hand, the pyloric pressure during the course of stimulation (70.43±23.09mmHg) was significantly lower than that before the stimulation (90.40±16.56mmHg). GES had no effects on the contraction frequencies of antrum and pylory.Part Ⅲ: The concentrations of ghrelin, GLP-1, obstatin, resistin, leptin, PYY, leptin and insulin in surum and in the gastric tissue before and after GES have no statistically significant differences.Conclusion1. The animal model designed in this experiment could be used for GES and the testing of gastric accommodation and antral and pyloric pressure.2. The new type of adjustable GES stimulator could adjust the pulse widths and amplitude by a large margin, with the capability of offering the various stimulation modes that one may need.3. Pulse trains with wider pulse width could evidently inhibit food consumption of subject dogs without causing severe symptom and complication. The stimulation parameters selected varied among the subject dogs. This GES was found to be effective and safe and have a promising prospect for clinic application.4. Pulse trains with wider pulse width could increase the fasting gastric capacity, and change the gastric motility, which may be related to the reduction of food intake.5. GES had no significant impacts on gastrointestinal hormones in serum and gastric tissue.