38Gastric emptying response to temporary gastric electrical stimulation is independent of symptom improvement but dependent on baseline emptying

Introduction:  Gastric electrical Stimulation (GES) is an accepted therapy for drug refractory gastroparesis, but its effect on gastric emptying is controversial.
Patients:  To examine the effect of GES on GET we examined 140 consecutive patients undergoing temporary endoscopic GES as previously described (GIE 2005: 61:455–461). Pts were 29 m, 14 f, mean age 41 years with diagnosis (DX): 44 diabetes (DM), 14 post-surgical (PS) and 82 idiopathic (ID).
Methods:  Symptom Assessment, Gastric emptying and EGG were evaluated at baseline and after temporary endoscopic GES (mean 3 day of therapy). Patients at baseline were stratified into 3 groups based on GET: Delayed, Normal and Rapid, as previously described (AGC 2001: 95:1456–1461). Symptoms (SX) of nausea (N), vomiting (V), and total SX (TSS), and GET were compared by paired t-tests and reported as mean values.
Results:  All patients had Symptoms improvement, irrespective of their DX or baseline GET: (N: 3.5 baseline to 0.9 after; V: 2.5–0.6; TSS: 15.2–5.1 for all patients with uniform changes in subgroups. There were no significant changes in GET for the whole patient group. However, when stratified by baseline GET: the delayed group accelerated (and the rapid group slowed (see table).
Conclusion:  Temporary GES performed on patients with the SX of gastroparesis shows an immediate symptom improvement, which is independent of baseline GET. The effect of temporary GES on gastric emptying is dependent on baseline emptying, with improvements seen in both delayed and rapid gastric emptying sub-groups. Conclusions about the effect of electrical stimulation on gastric emptying need stratification for baseline gastric emptying.
 

     

39Gastrointestinal electrical stimulation in post-surgical gastroparesis improves symptoms independently while gastric emptying response is dependent on baseline emptying

Introduction:  Temporary GES (tempGES) can improve both gastric emptying and symptoms in post-surgical gastroparesis (PS-GP). (SSAT 2004). Long-term effects on GI symptoms and gastric emptying are unknown. Since many PS-GP patients have non-delayed emptying, the long-term effect on baseline normal or rapid emptying is also unknown.
Patients:  36 pts (6 M, 30 F, mean age 42 years) with post-surgical: Bilroth I ( n  = 11), Bilroth II ( n  = 4), other gastric surgery ( n  = 21) disordered gastric emptying were evaluated.
Methods:  GI symptoms (vomiting = V, Total = TSS), and solid meal gastric emptying (GET) at 1 and 4 h, were compared at baseline (Base), after temporary (tempGES) and permanent (permGES) gastric electrical stimulation as previously described (NGM, 2004; 16: 635.) Long-term follow-up for permanent GES ranged from 6 month to 10 years. Results were compared by t-tests, and are reported as means ± SEM.
Results:  29 of the 36 patients were able to tolerate food for baseline quantitative gastric emptying testing. 20 patients had delayed and 9 patients had non-delayed gastric emptying, with 7/9 being rapid. With both tempGES and permGES, GI symptoms improved (p < 0.05). Both tempGES and permGES showed accelerated GET for delayed patients and generally slowed GET for non-delayed (p < 0.05 for 1 h values). See tables below.
Conclusions:  In a large group of post-surgical GP patients, temporary and permanent gastrointestinal electrical stimulation improved GI symptoms independent of gastric emptying and for a prolonged time. GES improves symptoms independent of baseline gastric emptying, and improves GET dependent on the baseline gastric emptying.
 

     

46The feasibility of duodenum electrical stimulation to produce gastrointestinal symptoms in a clinical trial

Introduction:  Gastric Electrical Stimulation (GES) is available as a Humanitarian Use Device for patients with the symptoms of gastroparesis and is effective in reducing gastrointestinal symptoms. We have previously shown that patients with gastric motor disorders often have co-existing abnormalities of the genitourinary system (Gastroenterol 112: A737, 1997), which may now be treated with sacral electrical stimulation (SES), resulting in similar improvements in genitourinary symptoms.
Patients:  We compared the results of therapy with GES and SES in 13 patients who were implanted with both devices. Patients were 11 f, 2 m, mean age of 41 years, who had documented gastroparesis as well as bladder or other pelvic floor dysfunction. All 13 patients had received their GES before the SES.
Methods:  Patients were evaluated at baseline and latest follow up (median 4 years for GES and 2 years for SES), according to previously standardized scores of GI (GI: 0–4, TSS max 20) and GU (GU: 0–3, UTSS, max 12) function. Results were compared by paired t-tests and reported as mean ± SE.
Results:  All 13 patients improved both GI and GU symptoms and the improvement in all parameters as nausea, vomiting, anorexia, bloating, abdominal pain and gastric total symptom score (TSS), leakage, urgency, voiding difficulty, number of pads used and urinary total symptom score (UTSS) were statistically significant (see table below).
Conclusions:  The combination of GES and SES appears to be both safe and effective for patients with con-comitant gastroparesis and bladder dysfunction and the existence of a stimulator for one disorder does not preclude another stimulator.
 

     

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.     

Variable abnormal physiological motility in the proximal upper gastrointestinal tract in gastroparesis

Background Traditional testing for gastroparesis with gastric emptying scintigraphy (GES) likely misses a subset of patients because of the heterogeneous nature of the disease. The primary aim of this study is to determine the prevalence of simultaneously measured transit and pressure abnormalities in patients with gastroparesis. The secondary aim is to assess diagnostic gain realized by measuring antroduodenal pressure and gastric transit with wireless motility capsule (WMC) compared to gastric transit measured by GES. Identification of abnormalities beyond gastric transit delay in gastroparesis may yield novel targets for pharmacological therapies. Methods Forty‐three subjects with symptoms of gastroparesis and previous abnormal GES within 2 years were enrolled in the study. Subjects underwent simultaneous GES and WMC to assess gastric transit. Gastric and small bowel pressure profiles were measured by WMC to determine the contribution of pressure to diagnostic gain realized with WMC. Key Results Fifty‐one percent of subjects had abnormal GES while 70% of subjects had either abnormal gastric emptying time (GET) or antroduodenal pressure. Gastric emptying time was abnormal in 60% of subjects while gastric or small bowel pressure was abnormal in 47% of subjects. The overall diagnostic gain of WMC compared to GES was 19% (P = 0.04). Seven percent of subjects had abnormal small bowel pressure profiles when both GES and GET were normal. Conclusions & Inferences (i) Gastroparesis is a heterogeneous disorder and testing only solid food emptying by scintigraphy may miss a significant amount of pathology. (ii) Measuring complementary aspects of gastric and small bowel function simultaneously results in greater detection of physiologic abnormalities that may underlie patient symptoms.     

Low-Resolution Electrogastrogram at Baseline and Response to Temporary Gastric Electrical Stimulation—A Comparison of Cutaneous With Mucosal Recordings

IntroductionGastric electrical stimulation (GES) is a widely accepted therapy for gastroparesis symptoms, but how a brief cutaneous electrogastrogram (EGG) can be used in conjunction with GES has not been well defined. We evaluated the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and gastrointestinal symptoms before and after temporary GES (tGES).Materials and MethodsWe studied 1345 patients; 991 had complete data. EGG measurements like frequency and amplitude were recorded at baseline and five days post-tGES using short recording periods. A total of 266 participants having additional cutaneous propagation values were separately analyzed. Patients underwent solid GET before and after tGES and self-reported symptoms using standardized traditional patient-reported outcomes (TradPRO) scores. Pearson correlations were assessed at baseline, post-stimulation, and their changes over the follow-up period.ResultsEGG measures correlated with symptoms and GET results. Patients with abnormal baseline cutaneous frequency had higher baseline total symptom scores (p < 0.003). Post-tGES, one-hour gastric emptying was significantly changed (p < 0.0001) and was mainly observed with abnormal baseline cutaneous frequencies (p < 0.0001). Cutaneous frequency significantly increased after tGES (p < 0.0001), correlating positively with TradPRO scores and one-hour gastric emptying. Mucosal and cutaneous measures correlated pre- and post-treatment. Of the 266 patients, 153 changed propagation states between baseline and temporary; changing states from lower at baseline to higher at temporary was more likely than vice versa. Short EGG recording times can demonstrate changes after the bioelectric therapy of GES.ConclusionEGG is valuable in the diagnosis of delayed gastric emptying and comparable with mEG. It is less invasive and can identify patients who may require GES. Frequency, amplitude, their ratio (frequency-amplitude ratio), and propagation appear to be reliable measures of EGG. EGG provides cost-effective measurement of electrophysiological properties and significantly correlates with important clinical measures. Shorter EGG recording times may be adequate to see changes from bioelectric therapies.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03876288.     

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying

Background Symptoms of gastroparesis based on patient recall correlate poorly with gastric emptying. The aim of this study is to determine if symptoms recorded during gastric emptying scintigraphy (GES) correlate with gastric emptying and with symptoms based on patient recall. Methods Patients undergoing GES completed the Patient Assessment of GI Symptoms (PAGI‐SYM) assessing symptoms over the prior 2 weeks and a questionnaire for which patients graded six symptoms during GES. A Symptom Severity Index (SSI) represented the mean of six symptoms at each time point. Key Results A total of 560 patients underwent GES for clinical evaluation of symptoms. Of 388 patients included in the study: 232 patients had normal GES (NGES), 156 delayed GES (DGES), and 11 rapid GES (RGES). Symptom severity index increased pre to postprandial for each group: NGES: 0.51 ± 0.07 to 0.92 ± 0.03, DGES: 0.60 ± 0.09 to 1.13 ± 0.05, and RGES: 0.56 ± 0.12 to 0.79 ± 0.13. Delayed gastric emptying scintigraphy patients had a higher postprandial SSI than NGES patients (1.13 ± 0.05 vs 0.92 ± 0.03, P < 0.05). Postprandial symptoms of stomach fullness (1.9 ± 0.12 vs 1.5 ± 0.09; P = 0.011), bloating (1.4 ± 0.11 vs 1.1 ± 0.09; P = 0.033), and abdominal pain (1.1 ± 0.08 vs 0.7 ± 0.12; P = 0.012) were higher in DGES than NGES. Symptom severity based on PAGI‐SYM for 2 weeks prior to GES correlated with symptoms during the test for nausea (NGES, r = 0.61; DGES, r = 0.70), stomach fullness (NGES, r = 0.47; DGES, r = 0.60), and bloating (NGES, r = 0.62, DGES, r = 0.66). Conclusions & Inferences Stomach fullness, bloating, and abdominal pain recorded during GES were higher in patients with delayed gastric emptying than in patients with normal gastric emptying. Symptoms recorded during GES correlated with those during daily life by patient recall.     

The addition of pyloroplasty as a new surgical approach to enhance effectiveness of gastric electrical stimulation therapy in patients with gastroparesis

Background Improvement of gastroparesis (GP) symptoms has been documented in patients treated with gastric electrical stimulation (GES), but acceleration of gastric emptying (GET) is unpredictable. The aim of our study was to evaluate the advantage of adding surgical pyloroplasty (PP) to GES for improvement of GET and control of symptoms in diabetes mellitus (DM), idiopathic (ID), and postvagotomy (P‐V) GP. Methods A total of 49 (17 – DM, 9 – ID, 23 – P‐V) consecutive GP patients: 38 female; mean age 42 (21–73 years); mean weight 158 lbs (102–245), underwent GES implantation, and 26 (53%) additionally received PP. Total Symptoms Score, 4‐h GET, adverse events (AEs), and days of hospitalizations were captured at baseline and at the last visit. Key Results The mean follow‐up was 7 months. Total Symptoms Score in patients who received Enterra and PP or GES alone significantly improved compared to their baseline scores (P < 0.001). GET improved by 64% at 4 h (P < 0.001) in patients with Enterra and PP, compared to 7% observed after GES therapy alone (ns). The most impressive acceleration of GET was seen in the P‐V group, who received both therapies (P = 0.004) and 8 (60%) of them normalized GET. No AEs accompanied the addition of PP to the Enterra surgery. Conclusions & Inferences (i) In drug‐refractory GP the addition of PP to GES substantially accelerated GET; (ii) The GET response in P‐V group was the most impressive; (iii) Significant symptom reductions were achieved by both procedures; and (iv) PP added to GES may sustain better long‐term symptoms control particularly in the P‐V setting.     

3Predictors of symptom non-responders to high-frequency gastric electrical stimulation for refractory gastroparesis

Chronic high‐frequency gastric electrical stimulation (GES) has been shown to improve gastroparetic symptoms and quality of life (QOL) in up to 70% of patients with refractory gastroparesis (Gastroenterology 2003; 125:421–8). Little is known about factors associated with treatment failure. Clinical and gastric function data (gastric emptying test, GET; electrogastrogram, EGG) were extracted from a retrospective analysis of 87 gastroparetic patients (48 diabetic, 20 idiopathic and 19 postsurgical) who completed GES therapy (Enterra? System, Medtronic) for at least 1 year. Total symptom score (TSS) (sum of severity of nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain and burning using a 5‐point scale, 0 = non, 4 = extremely severe), quality of life (SF‐36 Health Status Survey questionnaire including physical composite score (PCS) and mental composite score (MCS)) and GET (4‐hour scintigraphy of a low‐fat meal) were examined at baseline and 1 year follow‐up. A non‐responder had <25% reduction in TSS and a responder was defined as having a ≥ 50% reduction in TSS after 1 year of GES therapy. Results: Overall the non‐responder rate was 23% (10% in diabetic vs. 16% in postsurgical vs. 35% in idiopathic subgroup). Non‐responder rates were similar for men (22%) and women (23%) and age was not a factor. Compared to responders of GES therapy, non‐responders had similar mean baseline vomiting (2.6 vs. 3.2) and nausea scores (3.3 vs. 3.6) but a lower TSS (17.6 vs. 20.1, P < 0.05). Also non‐responders had less improvements in mean gastric retention both at 2 hours (+5.4 vs. ­8.7%) and at 4 hours (+4.0 vs. ­10.5%), less improvement in mean PCS (+2.0 vs. +12.4, P < 0.05) and gained less weight (­0.4 kg vs. +3.7 kg) than responders. 67% of non‐responders had an abnormal EGG (dysrhythmia >30% or decrease in postprandial EGG power) vs. 33% in responders. Non‐responders had more baseline mean tachygastria both in the fasting state vs. responders (26% vs. 11%, P < 0.05) and in the fed state (24% vs. 11%, P < 0.05) and less increase in postprandial EGG power (­1.3 dB vs. 1.6 dB, P < 0.05). Conclusions: The best symptom improvement achieved by high‐frequency GES therapy in refractory gastroparesis is in diabetics (10% treatment failure rate) and postsurgical (16% failure) while the worst results are in idiopathics (35% non‐responder rate). Baseline EGG abnormalities are predictors of poor symptomatic response to GES therapy and may be useful in developing a patient profile to optimize selection and expectations for GES therapy.     

Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis

Abstract  Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4-h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC− group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC− group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC− group was significantly more than in the ICC+ group both in the fasting (32 ± 8% vs 11 ± 2%) and fed states (27 ± 9% vs 12 ± 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.     

23A multi-component model can predict gastric emptying in diabetic gastroparesis

Introduction:  We have previously reported that a multi-component model of autonomic and enteric factors can help predict gastric emptying in diabetes mellitus. (Aslam N. Abell T. A four component model can quantitatively profile gastric emptying in diabetic gastropathy. Supplement to Gastroenterology Vol 118, April 2000, Number 4, Suppl 2. (Abstract No. 5341).
Patients:  Eighty-seven patients with Diabetes mellitus presenting with signs and symptoms of Gastroparesis. It included 38 males, 49 females with mean age of 39 ± 10 years.
Methods:  Autonomic tests included adrenergic tests by VC (vasoconstriction to cold) and PAR (postural ratio), and cholinergic function measured by EKG R to R interval (RRI). The Enteric measure (EGG) was measured by cutaneous electrogastrogram. The data was compared to results of standardized solid gastric emptying T50 in minutes (GE above), by linear regression.
Results:  The patients were distributed in five groups according to mean T50 of solid gastric emptying: 24 (28%) were very delayed, 13 (15%) delayed, 19 (22%) were normal, 15 (17%) were rapid, and 16 (18%) very rapid. There were statistically significant differences among the five group means for VC, RRI, and EGG, but not for PAR. (See table).
Conclusions:  In this group of patients with symptoms of Diabetic gastropathy, there is a wide range of gastric emptying values. A multi-component model demonstrates specific autonomic and enteric differences in subgroups of diabetic gastroparesis. Therapies for diabetic gastropathy, including drug and device studies, may need to take into account these physiologic differences when looking at therapeutic outcomes. Autonomic and enteric measure appear useful as part of the evaluation of patients with symptoms of diabetic gastropathy.
Means
 

     

Is symptom relief associated with reduction in gastric retention after gastric electrical stimulation treatment in patients with gastroparesis? A sensitivity analysis with logistic regression models

Background Enterra gastric electrical stimulation (GES) is an alternative treatment for gastroparesis (GP) when standard medical therapy fails. The aims of this study were to evaluate the association between total symptom score (TSS) and reduction in gastric retention (GR) after GES by GP etiology and to examine the sensitivity of the association to varying cutpoints used to define GR and TSS improvement. Methods Gastric retention assessed with a standardized ^99mTc radio‐labeled egg meal and TSS measured by a five‐point Likert scale in 221 GP patients treated with Enterra GES therapy for at least 1 year were analyzed. Bivariate chi‐square test and multivariable logistic regression with all possible cutpoints were used to assess the consistency of association and quantitate the relationship across three GP etiologies. Key Results Symptom relief in diabetic GP was more likely attributable to GR reduction as indicated by the consistently significant odds ratios (P < 0.01) across all cutpoints. The association in idiopathic GP was inconclusive because odds ratios were sensitive to cutpoints with P‐values ranging from 0.01 to 0.47. No association was found for patients with post surgical gastroparesis (P > 0.1 for all cutpoints). Patient age, gender, baseline TSS and baseline GR had no significant effect at 5% level on clinical improvement regardless of cutpoints for GR. Conclusions & Inferences Association between clinical improvements and GR reduction following GES treatment depends on patient etiology and was able to be demonstrated in diabetic GP. The association for idiopathic GP was inconclusive and no such association was found for post surgical GP across all possible cutpoint combinations.     

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.     

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 Neuromodulation With Enterra System for Nausea and Vomiting in Patients With Gastroparesis

Objective: Gastric electrical stimulation (GES) has been introduced for treating gastric motility disorders, such as gastroparesis, and obesity. A special method of GES using high frequency‐short pulses, called Enterra® Therapy, has been clinically applied to treat nausea and vomiting in patients with gastroparesis. However, its mechanisms are not well understood. Materials and Methods: General methodologies of GES published in the literature are systematically reviewed and their main effects and application are presented. The major part of this review is focused on Enterra Therapy since this is the only method that has been used clinically. A number of different GES methods have been proposed. Results: GES with long pulses or dual pulses, but not short pulses, are able to alter (enhance or inhibit) such parameters of gastric motility as gastric slow waves and gastric emptying. Synchronized GES has been reported to improve antral contractions. GES with high frequency‐short pulses, or Enterra Therapy, is known to improve nausea and vomiting in patients with gastroparesis and has a response rate of 50–70%. Improved gastric accommodation, direct enteric nervous system effects, enhanced vagal activity, and activation of central neurons are believed to be the underlying mechanisms involved in the antiemetic effect of this therapy. Conclusions: GES with high frequency‐short pulses effectively reduces nausea and vomiting in patients with gastroparesis. This antiemetic effect could be mediated via enteric, autonomic, and/or central neural mechanisms. Further systematic and controlled studies are needed to improve the efficacy of Enterra Therapy and to understand its mechanisms of action.     

Helicobacter pylori infection and gastric emptying of solids in humans

Helicobacter pylori has been implicated in a number of upper gastrointestinal illnesses. In a controlled study, we have investigated the relationship between H. pylori infection and gastric emptying of solids in two groups of patients with chronic symptoms of dyspepsia. In the first group, 19 patients with non-ulcer dyspepsia and H. pylori infection underwent a standard test of gastric emptying after ingestion of 500 μCi of Tc-labelled chicken liver. The results were compared to a control group of 16 uninfected volunteers. We also studied a second group of 20 patients with previously diagnosed idiopathic gastroparesis for the prevalence of H. pylori infection and its relationship to symptom severity and rates of gastric emptying. In the first group of patients, the half-time of gastric emptying was significantly less among the infected patients compared to the uninfected volunteers (108 ± 9 vs. 142 ± 14 min, P < 0.05). In the second group of patients with gastroparesis, the prevalence of H. pylori was not significantly different among these patients than among 21 age and sex matched controls (20% vs. 38%, P = 0.32). Gastric emptying was markedly slow in all 20 patients in the second group but less so among the four with H. pylori infection. Symptom scores were no different between infected and uninfected patients. We conclude that H. pylori infection is not associated with abnormally slow gastric emptying. On the contrary, gastric H. pylori infection appears to be associated with mildly accelerated emptying of solids compared to normal controls. Idiopathic gastroparesis and dyspepsia related H. pylori infection are separate but sometimes overlapping disorders.     

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.     

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.     

Effects and mechanisms of long-pulse gastric electrical stimulation on canine gastric tone and accommodation

Gastric electrical stimulation (GES) has been applied to treat gastroparesis and morbid obesity. The aims of this study were to evaluate the sites of stimulation and the mechanisms of GES on gastric tone and accommodation. Gastric tone and accommodation were evaluated with a barostat in surgically prepared dogs. GES was applied at seven different locations, and gastric tone was assessed at each site. The effect of truncal vagotomy on gastric tone and accommodation and the role of the nitrergic pathway were also evaluated. We have found: 1) GES induced varying degrees of gastric relaxation at all tested locations in normal dogs; 2) Gastric volume was also significantly increased with GES in vagotomized dogs and the change tended to be lower than that of normal animals; 3) Gastric accommodation was reduced during GES in both the normal and vagotomized dogs and the reduction tended to be more in the vagotomized animals; 4) The GES-induced increase in gastric volume was partially abolished by intravenous nitric oxide synthase inhibitor. GES at various sites of the stomach exerts inhibitory effect on gastric tone; the most effective sites are in the antrum along the lesser or greater curvature; the inhibitory effect of GES on gastric tone is partially mediated by the vagal and nitrergic pathway.     

The effects of tegaserod, a 5-HT4 receptor agonist, on gastric emptying in a murine model of diabetes mellitus

The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5-HT(4) receptor partial agonist, on gastric emptying. METHODS: Gastric emptying rates of a 20% glucose test meal were determined in 12-20-week-old female db/db mice and control littermates. The effects of tegaserod (0.1-2.0 mg kg(-1), i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5-HT(4)antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying. RESULTS: Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. CONCLUSIONS: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.