Effects of gastric electrical field stimulation with long pulses on gastric emptying in dogs

The aim was to investigate the effects of electrical field stimulation (EFS) with long and short pulses on gastric emptying, gastric contractility and vagal activity in dogs. Sixteen dogs were equipped with a duodenal cannula, electrodes and strain gauges (10 dogs) in the stomach. Each dog was fed with Ensure and gastric effluent was collected from the cannula. Electrical stimulation was applied via two electrodes (about 12 cm apart, one in the corpus and the other in the antrum) with long pulses (a frequency of 6 cycles min-1, pulse amplitude of 6 mA and width of 100 ms) in 10 dogs and with short pulses (frequency of 30 Hz and pulse width of 300 micros) in six dogs. The electrocardiogram was also recorded and heart rate variability was derived to assess the vagal activity. It was found that: (i). EFS with long pulses did not alter gastric emptying during stimulation but increased gastric emptying during the 45 min immediately after stimulation; (ii). EFS with long pulses increased gastric contractility in both proximal and distal antrum during and after the stimulation; (iii). EFS with long pulses resulted in an increase in vagal tone during the 45 min immediately after stimulation. However, there is no difference during the 45 min period of stimulation; (iv). EFS with short pulses had no effect on gastric emptying. We concluded that long pulse gastric electrical field stimulation with one electrode in the corpus and the other electrode in the antrum has postponed effects on gastric emptying of liquid, gastric contractility and vagal activity.     

Effects of vasopressin and long pulse–low frequency gastric electrical stimulation on gastric emptying, gastric and intestinal myoelectrical activity and symptoms in dogs

The aim of this study was to investigate the effect of vasopressin and long pulse-low frequency gastric electrical stimulation (GES) on gastric emptying, gastric and intestinal myoelectrical activity and symptoms in dogs. The study was performed in eight healthy female dogs implanted with four pairs of gastric serosal electrodes and two pairs of small bowel serosal electrodes, and a duodenal fistula for the assessment of gastric emptying. Each dog was studied in three sessions on three separate days in a randomized order with recordings of gastric and small bowel slow waves. Each study session consisted of 30-min baseline, 30-min stimulation and 30-min recovery period. In sessions 1 and 2, infusion of either saline or vasopressin (0.75 U kg(-1) in 30 mL saline instilled in 30 min) was given during the second 30-min period. The protocol of session 3 was the same as session 2 except long pulse-low frequency GES was performed during the second 30-min period. It was found that: (i) Vasopressin significantly delayed gastric emptying 30 and 45 min after meal and GES did not improve the vasopressin induced delayed gastric emptying; (ii) Vasopressin induced gastric dysrhythmias and GES significantly improved vasopressin induced gastric dysrhythmia; (iii) Vasopressin also induced intestinal slow wave abnormalities but GES had no effect on vasopressin induced small bowel dysrhythmia; (iv) Vasopressin induced symptoms and behaviours suggestive of nausea that were not improved by GES. We conclude that: (i) Vasopressin delays gastric emptying and induces gastric and small bowel dysrhythmias and symptoms in the fed state, and (ii) long pulse-low frequency GES normalizes vasopressin induced gastric dysrhythmia with no improvement in gastric emptying or symptoms.     

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

Background 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. Methods 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. Key Results (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. Conclusions & Inferences 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.     

Comparative gastric motility study of EnterraTM Therapy and neural gastric electrical stimulation in an acute canine model

Background Gastric electrical stimulation (GES) is an avenue for treating gastroparesis and obesity by controlling gastric motility using electrically mediated gastric contractions. Neural gastrointestinal electrical stimulation (NGES) is a GES modality capable of producing strong lumen‐occluding local gastric contractions. Conversely, Enterra^TM Therapy, a commercial implantable gastric electrical stimulator, has been utilized to treat symptoms of gastroparesis, but its nominal electrical parameters are not capable of generating lumen‐occluding contractions. However, comparative studies between these two stimulation modalities are lacking. Methods Strain gauge transducers complemented by endoscopic monitoring have been utilized to register gastric contractions invoked with NGES and Enterra neurostimulators in four acute dogs. Mucosal and serosal electrode implantations, ‘nominal’ and ‘maximum’ electrical parameters, and longitudinal and transverse electrode placements have been tested with each neurostimulator type. Key Results Strong lumen‐occluding, circumferential contractions were induced with a wide variety of NGES parameters utilizing both transverse and longitudinal electrode configurations from the serosal side of the stomach. Similarly, local gastric contractions were observed with the Enterra neurostimulator programmed at its ‘maximum’ electrical parameters but only when utilizing transverse serosal electrode implantation. Under ‘maximum’ electrical parameters Enterra was not capable of producing registerable gastric contractions with longitudinally implanted serosal electrodes. Mucosal electrode implantations did not result in GES‐invoked gastric contractions in both stimulation modalities. Conclusions & Inferences Enterra Therapy is capable of producing gastric contractions under ‘maximum’ parameters and transverse electrode configuration. Neural gastrointestinal electrical stimulation produces stronger, lumen‐occluding contractions under a wider range of electrode configurations and parameters.     

Effects and mechanisms of vaginal electrical stimulation on gastric tone in dogs

Abstract  Electrical stimulation of one part of the gut may have beneficial or adverse effects on another region. We hypothesized that electrical stimulation of a visceral organ in one system might have an effect on another visceral organ system. That is, disorders of one system may be treated by interventions of another system and this may lead to a more convenient or less invasive therapies in some cases. The aim of this study was to evaluate the effects and mechanisms of vaginal electrical stimulation (VES) with different parameters on gastric tone and gastric slow waves in conscious dogs. Seven dogs were studied in two experiments. Experiment 1 was to study effects of VES on gastric tone and slow waves. Experiment 2 was performed in two sessions (long pulse VES plus guanethidine and VES with trains of long pulse plus guanethidine) to study involvements of possible sympathetic mechanisms. The results of our experiments were: (i) VES increased the gastric volume in a dose-dependent manner with the increase of stimulation frequency, amplitude or pulse width; (ii) VES had no effects on gastric slow waves; (iii) the inhibitory effect of VES with long pulses or trains of long pulses on gastric tone was abolished by guanethidine; and (iv) few or mild symptoms were noted with stimulation. VES decreases proximal gastric tone in an energy-dependent manner without affecting gastric slow waves. The inhibitory effect of VES is mediated by a sympathetic pathway. Hypertensive gastric tone might be treated using electrical stimulation of the vagina which is minimally invasive.     

Intestinal electrical stimulation improves delayed gastric emptying and vomiting induced by duodenal distension in dogs.

The aim of this study was to investigate the effects of short-pulse intestinal electrical stimulation (IES) on duodenal distention-induced delayed gastric emptying and vomiting in dogs and its possible mechanisms. The study was performed in 12 dogs with jejunal electrodes and a duodenal cannula in three separate experiments to investigate the effects of IES on duodenal distension (DD)-induced delayed gastric emptying and discomfort signs, vagal efferent activity, and jejunal tone. We found that: (i) IES significantly accelerated gastric emptying of liquid delayed by distension (18.05 +/- 4.06%vs. 7.18 +/- 1.99%, P = 0.036 at 60 min). (ii) IES significantly reduced vomiting and discomfort/pain induced by distension. The average signs score was 15.33 +/- 1.37 during distension which decreased to 6.50 +/- 0.91 (P = 0.0002) with IES. (iii) IES did not change vagal afferent activity, which was assessed by the spectral analysis of the heart rate variability. (iv) IES decreased jejunal tone. In conclusion, IES with parameters commonly used in gastric electrical stimulation for nausea and vomiting associated with gastroparesis improves DD-induced delayed gastric emptying and prevents DD-induced vomiting and discomfort signs. Further studies are warranted to investigate the therapeutic potential of IES for gastrointestinal symptoms associated with disturbances in motility and sensory function in small intestine.     

Efficiency and efficacy of multi-channel gastric electrical stimulation

Gastric electrical stimulation (GES) using single channel has been under investigation for its therapeutic potential for gastroparesis. The aim of this study was to study the efficacy and efficiency of multi-channel GES in accelerating gastric emptying in dogs. The study was performed in eight dogs, and gastric emptying of liquid was assessed in three randomized sessions of control, one-channel GES and four-channel GES. It was found that (i) GES of both one-channel and four-channel was able to completely entrain the slow waves in the entire stomach. However, the stimulation energy required by four-channel GES was only 1% of that required by one-channel GES. (ii) Four-channel, but not one-channel, GES significantly and substantially accelerated gastric emptying. An increase of 121.0 and 93.9% was noted with four-channel GES at 30 and 60 min after the meal, respectively. It was concluded that four-channel GES is substantially more efficient and effective than conventional single-channel GES in improving gastric emptying. It is worthy to explore its therapeutic potential for gastroparesis in clinical settings.     

Gastric electrical stimulation at proximal stomach induces gastric relaxation in dogs

Gastric electrical stimulation (GES) improves symptoms in patients with gastroparesis. However, the underlying mechanisms remain unclear. To determine if GES at proximal and distal stomach could affect the biomechanical properties of the stomach, thus contributing to the beneficial effect of GES. Four pairs of electrodes were implanted along the greater curvature of the stomach in seven dogs. Gastric tone and compliance was assessed with a barostat. Measurements were obtained randomly during control and proximal and distal stimulation (4 mA, 375 ms and 6/18 cpm). Data as mean or median (25-75th percentiles). Gastric compliance was not affected by proximal and distal GES. Gastric tone was significantly reduced during proximal GES: 82.0 (66.8, 89.1) mL vs control 49.7 (39.6,75.9) mL at 6 cpm (P = 0.016), and 90.6 (54.5, 117.9) mL vs control 62.8 (39.6, 75.9) mL at 18 cpm (P = 0.031). Tone was not affected by distal GES at 6 cpm: 95.8 (46.3, 106.7) mL vs control 75.2 (49.7, 86.1) mL (P = 0.47) and at 18 cpm: 80.4 (38.1, 170.3) mL vs control 62.8 (44.6, 156.3) mL (P = 0.44). Proximal GES induces gastric relaxation. This effect, if seen also in humans, may explain, in part, the symptomatic improvement associated with GES therapy in patients with gastroparesis.     

Circadian patterns of gastric electrical and mechanical activity in dogs.

Gastric motor function assessment, in humans and animals, is typically performed for short recording periods. The aim of this article was to monitor gastric electrical and motor activity in the antrum and fundus simultaneously, for long periods, using a new implantable system. Ten dogs were implanted with fundic and antral electrodes for assessment of impedance and electrical activity. Dogs were studied while in cages, for periods of 22-26 h. From late evening and until feeding on the next day, slow wave (SW) rhythm demonstrated a distinct pattern of intermittent pauses (mean duration = 22.8 +/-4.1 s) that delineated groups of SW's. Phasic increases in fundic tone were seen mostly in association with SW pauses, and were highly correlated with antral contractions, R(2) = 0.652, P < 0.05. The SW rate (events per minute) in the postprandial period, fasting and night time was 4.2 +/- 0.2, 5 +/- 0.2 and 4.7 +/- 0.3, respectively, P < 0.05 postprandial vs other periods. Antral and fundic mechanical activities were highly correlated during fasting, particularly at night. This novel method of prolonged gastric recording provides valuable data on the mechanical and electrical activity of the stomach, not feasible by current methods of recording. During fasting, fundic and antral motor activities are highly correlated and are associated with periodic pauses in electrical activity.     

Efficacy and efficiency of gastric electrical stimulation with short pulses in the treatment of vasopressin-induced emetic responses in dogs

The aim of this study was to determine the most effective and efficient anti-emetic parameters of short-pulse gastric electrical stimulation (GES) in dogs. Seven female beagle dogs implanted with four pairs of gastric electrodes were studied in eight randomized sessions (saline, vasopressin, and six GES sessions with different parameters). Each session consisted of four 20-min recordings of gastric slow waves and symptoms. In sessions 1 and 2, saline and vasopressin, respectively, were infused during the second 20-min period. The protocol of the other six sessions was the same as session 2 except that GES was continuously applied. It was found that: (1) vasopressin induced gastric dysrhythmia and emetic response (P < 0.01, anova); (2) short-pulse GES with a frequency of 14 or 40 Hz and pulse width of 0.1 or 0.3 ms, but not 0.6 ms was able to reduce symptoms induced by vasopressin; (3) short-pulse GES with a pulse width of 0.3 ms was the most effective in preventing vasopressin-induced symptoms; (4) none of the tested GES methods improved vasopressin-induced gastric dysrhythmia. We conclude that vasopressin induces gastric dysrhythmia and symptoms. Short-pulse GES with a pulse width of 0.3 ms and frequency of 14 Hz is most effective and efficient in preventing vasopressin-induced emetic responses in dogs.     

Effect of high-frequency gastric electrical stimulation on gastric myoelectric activity in gastroparetic patients

The aim of this study was to investigate the effect of gastric electrical stimulation (GES) on gastric myoelectric activity (GMA) and to identify possible mechanisms that could help explain how high-frequency GES is effective in treating nausea and vomiting associated with gastroparesis. Fifteen gastroparetic patients who received high-frequency GES were enrolled. Two pairs of temporary pacing wires were implanted on the serosa of the stomach along the greater curvature during surgery for placement of the permanent stimulation device. Two-channel serosal recordings of GMA before and during GES were measured. A gastric emptying test and severity of nausea and vomiting were assessed at baseline and at 3 months of GES. Power spectral and cross correlation analyses revealed that impaired propagation of slow waves (50%), tachygastria (30%) and abnormal myoelectric responses to a meal (50%) were the main abnormalities observed at baseline. GES with a high frequency significantly enhanced the slow wave amplitude and propagation velocity, and resulted in a significant improvement in nausea and vomiting but did not entrain the gastric slow wave or improve gastric emptying after 3 months of GES.     

Delayed gastric emptying rates and impaired antral motility in children fulfilling Rome III criteria for functional abdominal pain

Background Gastric sensorymotor dysfunctions have been implicated in the pathophysiology of some functional gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome. Therefore, we hypothesized that abnormal gastric emptying and impaired antral motility are possible underlying mechanisms of symptoms in children with functional abdominal pain (FAP). Methods Hundred and two children [37 (36.3%) males, 4–14 years, mean 7.8 years, SD 2.7 years] fulfilling Rome III criteria for FAP were recruited for this study. An age and sex compatible group of healthy children (n = 20) were selected as controls [8 (40%) males, 4–14 years, mean 8.4 years, SD 3.0 years]. Liquid gastric emptying rate (GER) and antral motility parameters (amplitude of antral contractions, frequency of antral contractions and antral motility index) were assessed using a previously reported ultrasound method. Key Results Average GER (42.1% vs 66.2% in controls), amplitude of antral contractions (56.5% vs 89%), frequency of contractions per 3 min (8.5 vs 9.3), and antral motility index (4.9 vs 8.3) were significantly lower in patients with FAP compared with controls (P < 0.01). Fasting antral area was higher in patients (1.4 vs 0.6, P < 0.0001). GER negatively correlated with the scores obtained for severity of abdominal pain (r = ?0.29, P = 0.004). Conclusions & Inferences Gastric emptying rate and antral motility parameters were significantly impaired in patients with FAP and GER negatively correlated with symptom severity. These findings highlight the possible role of gastrointestinal motility abnormalities in the pathophysiology of childhood FAP.     

An energy algorithm improves symptoms in some patients with gastroparesis and treated with gastric electrical stimulation

Gastric electrical stimulation (GES) is effective to improve symptoms of nausea and vomiting in most patients, but very little is known about the effect of varying stimulation parameters. We analysed stimulation parameters in a pilot study of 22 patients (12 idiopathic, four diabetic and four postsurgical) with drug-refractory gastroparesis who did not respond optimally to initial settings. Patients underwent high-frequency/low energy GES using identical initial stimulation parameters: 5 mA of current, 330 micros pulse width, 14 Hz for 0.1 s on and 5.0 s off. Due to lack on optimal response, 22 patients underwent alteration of an algorithm using stimulation parameters. At follow-up (mean of 4.3 years) a dose-response relationship for charge, power and energy were compared with baseline for the whole group and for each diagnostic subgroup by anova data are reported as mean +/- SE. Based on the mean of individual dose-response curves, differences in data are charge, current per pulse and energy per pulse were noted for the whole group at follow up vs baseline. The subgroup of patients with postsurgical gastroparesis required the most energy using the algorithm. In conclusion, an algorithmic approach to identify optimal stimulation parameters in GES for individual patients is associated with symptom improvement. Also, certain subgroups appear to have different energy parameters. Based on this preliminary data, the use of an algorithm for some patients with GES is feasible and may have potential for clinical application. A randomized-controlled trial of different stimulation parameters for GES seems warranted.     

Association between changes in symptoms and gastric emptying in gastroparetic patients treated with gastric electrical stimulation

Abstract  To investigate whether there is an association between gastric emptying rate and symptom improvement in gastroparetic patients treated with gastric electrical stimulation (GES), we retrospectively reviewed 63 gastroparetic patients who received GES therapy for at least 1 year. Patient characteristics, seven upper gastrointestinal (GI) symptoms and 4-h standardized gastric emptying test (GET) were evaluated at baseline and at 1 year of GES. All symptoms were significantly reduced ( P  <   0.001). Mean gastric retention was reduced by 7% ( P  =   0.102) for measurement at 4 h. Of the 63 patients, 14 had their GET normalized and 49 remained delayed after 1 year. Normalized GET patients had a similar symptom improvement as those whose GET remained delayed. Of all upper GI symptoms, the improvements in vomiting ( P  =   0.04), nausea ( P  =   0.002) and epigastric pain ( P  =   0.001) were significantly correlated with reduction in 4-h gastric retention between baseline and 12 months of GES therapy for patients with normalized gastric emptying but there were no correlations with any symptoms and change in gastric emptying for those patients who remained delayed. In summary, overall gastric emptying is not significantly accelerated at 4 h after successful symptomatic improvement with GES but nausea, vomiting and epigastric pain can be correlated with normalization of GET in a subset of patients.     

Dual pulse intestinal electrical stimulation normalizes intestinal dysrhythmia and improves symptoms induced by vasopressin in fed state in dogs

To assess effects of dual pulse intestinal electrical stimulation (DPIES) on intestinal dysrhythmia and motility, and symptoms induced by vasopressin in conscious dogs. The study was performed in three postprandial sessions (control; vasopressin; DPIES) in six dogs with two pairs of electrodes chronically implanted on the serosal surface of the proximal jejunum and with a chronic duodenal fistula. A manometric catheter was advanced into the small intestine via the intestinal cannula. Motility and intestinal slow waves were recorded. Symptoms were assessed. During vasopressin infusion, the percentage of normal intestinal slow wave frequency was decreased (P < 0.01), reflected as a significant increase in the percentage of both bradygastria and tachygastria; the motility index decreased (P < 0.01) and the symptom score increased (P < 0.01). In the session of DPIES, the percentage of normal slow wave frequency was recovered (P < 0.05 vs vasopressin), attributed to a reduction in both bradyarrhythmia and tachyarrhythmia; the symptom score was reduced (P < 0.05 vs vasopressin); the motility index was not significantly increased. These results suggest that vasopressin induces intestinal dysrhythmia and emetic symptoms and inhibits intestinal motility. Dual pulse intestinal electrical stimulation is capable of improving intestinal dysrhythmia and emetic symptoms but not impaired intestinal motility induced by vasopressin.     

Video-based spatio-temporal maps for analysis of gastric motility in vitro: effects of vagal stimulation in guinea-pigs

Our aim was to evaluate topographically specific gastric motility changes induced by graded vagal activation. A recently developed method of constructing spatio-temporal maps of motility from video movies was adapted to the in vitro perfused guinea-pig stomach with an intact vagal nerve supply. In the unstimulated preparation, spontaneous activity was low or absent. Bilateral vagal stimulation with frequencies as low as 0.2 Hz triggered weak anally, and in some cases orally, propagating antral contractions at rates of about 5-6 min-1. Upon stimulation with higher frequencies, antral contractions increased significantly in length (starting more proximally) and amplitude, and produced large pressure peaks of up to 25 hPa, with maximal effects at 2-4 Hz. In contrast, the speed of propagation and the interval between peristaltic waves did not change with vagal stimulation at any frequency. Vagal stimulation also produced a significant and frequency-dependent enlargement of the fundus with a maximal effect at 4 Hz. It is concluded that a very low tonic vagal activity is apparently necessary and sufficient to express basic antral motility, while more sustained vagal activity is necessary for high-amplitude gastric contractions and significant sustained fundic relaxation. The constant interval between propagating contractions supports the concept that vagal input impinges on intrinsic enteric neural circuits that have a modulatory role in the myogenic mechanism underlying slow-wave peristalsis, rather than directly on gastric musculature.     

Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis

The aims were to determine symptom responses and long-term outcomes in gastroparetic patients receiving gastric electrical stimulation (GES) therapy beyond 3 years by presenting per protocol analysis and intention-to-treat (ITT) analysis. Data collected at baseline, 1 year and beyond 3 years in 55 patients included total symptom scores (TSS), nutritional status, weight, hospitalizations, the use of prokinetic and/or antiemetic medications, HbA1c in diabetics and adverse events. Of the 55 patients, 10 died of non-pacemaker-related complications, six had the devices removed and two could not be reached. The remaining 37 patients had the device activated for a mean of 45 months. Both per protocol and ITT analysis demonstrated that TSS, hospitalization days and the use of medications were all significantly reduced at 1 year and were sustained beyond 3 years. Average TSS decreased by 62.5% for the 37 patients completing 3 years of GES. At implantation, 15/37 patients required nutritional support and only five continued beyond 3 years. Mean HbA1c level in diabetics was significantly reduced from 9.5 to 7.9% at 3 years. We conclude that a significant improvement in symptoms and all measures of clinical outcome can be maintained for greater than 3 years with GES in patients with refractory gastroparesis.