Gastric Dysrhythmias Research Articles

Study of the regulatory effect of acupuncture on rotation-induced gastric dysrhythmia in rabbits.

A model of experimental gastric dysrhythmia in rabbits was set up to evaluate the effect of different acupoints on regulating gastric dysrhythmia in rabbits so as to promote acupuncture treatment for this kind of disease. A model of gastric dysrhythmia in rabbits was established by the rotation method using the basic electrical rhythm (BER) as an objective index. After puncturing at the points of Zusanli (ST36), Neiguan (PC6), Tiaokou (ST38) and Tianquan (PC2) in the four groups of experimental gastric dysrhythmia rabbits, the difference in regulatory effects on the disturbance and frequency of the gastric electric slow wave was observed. Before needling at the specific acupoints Zusanli and Neiguan, the percentage of disturbance electric slow wave for the Zusanli and Neiguan groups was 57.0785 ± 10.644 and 55.5173 ± 6.0500, respectively; after such needling, the percentage was 43.7823 ± 10.1518 and 43.5147 ± 6.8983 for the Zusanli and Neiguan groups, respectively, while the frequency of electric slow wave for the Zusanli and Neiguan groups was 2.2870 ± 0.3800 and 2.4020 ± 0.3536, respectively, before needling and after needling, the frequency was 2.7090 ± 0.5865 and 2.9220 ± 0.4923 for the Zusanli and Neiguan groups, respectively. Comparing the percentage and frequency for the Zusanli and Neiguan groups before and after needling, the result shows that both groups have a significant difference statistically (P < 0.05) but between the Zusanli and Neiguan groups, there was no significant difference. Before and after needling the nonspecific acupoints of Tiaokou and Tianquan, there was no difference between the Tiaokou and Tianquan groups. Between the Zusanli and Tiaokou groups and the Neiguan and Tianquan groups, there are significant differences in regulating gastric dysrhythmia. This model is suitable for the observation of gastric dysrhythmia. The specific acupoints of Zusanli and Neiguan have good effects on the treatment of gastric dysrhythmia.

A Multiscale Model of the Electrophysiological Basis of the Human Electrogastrogram

The motility of the stomach is coordinated by an electrical activity termed “slow waves”, and slow-wave dysrhythmias contribute to motility disorders. One major method for clinically evaluating gastric dysrhythmias has been electrogastrography (EGG); however, the clinical utility of EGG is limited partly due to the uncertainty regarding its electrophysiological basis. In this study, a multiscale model of gastric slow waves was generated from a biophysically based continuum description of cellular electrical events, coupled with a subject-specific human stomach model and high-resolution electrical mapping data. The model was then applied using a forward-modeling approach, within an anatomical torso model, to define how slow wave activity summates to generate the EGG potentials. The simulated EGG potentials were shown to be spatially varying in amplitude (0.27–0.33 mV) and duration (9.2–15.3 s), and the sources of this variance were quantified with respect to the activation timings of the underlying slow wave activity. This model constitutes an improved theory of the electrophysiological basis of the EGG, and offers a framework for optimizing the placement of EGG electrodes, and for interpreting the EGG changes occurring in disease states.

Pathophysiological and Psychosocial Study in Patients With Functional Vomiting

Background/AimsTo explore clinical patterns, predisposing factors, psychosocial aspects and the possible pathogenesis in Functional Vomiting (FV) patients.MethodsTen healthy subjects and 19 FV patients participated in this study. Gastrointestinal symptoms and psychological state were evaluated by questionnaires, including Zung self-rating anxiety and depression scale and Eysenck personality questionnaire. Cutaneous electrogastrography, perfusion nutrition load test and intragastric pressure were performed in patients. Perfusion nutrition load test and intragastric pressure were also performed in healthy subjects.ResultsFV involved young female predominantly (4 male, 15 female; age 25.8 ± 8.4 years). Postprandial vomiting soon after meal without self-induced maneuver was the most common pattern of FV. Prevalence for overlaps between FV and functional dyspepsia was high (84.2%). Emotional changes and stress contributed to the development of FV. Prevalence of abnormal psychological status and personality in patients with FV was high (83.3% and 47.1%). Patients with FV had significant postprandial gastric dysrhythmia, impaired gastric accommodation and enhanced gastric sensitivity. There were significant correlations between clinical presentations, gastric function and psychological states.ConclusionsPatients with FV had abnormal psychological status, gastric dysmotility and hypersensitivity, which indicated that both of peripheral and central abnormalities could contribute to the pathogenesis of FV.

Telemetry in a motion‐sickness model implicates the abdominal vagus in motion‐induced gastric dysrhythmia

In humans, motion sickness is associated with disruption of normal gastric myoelectric activity, and it has been proposed that this results from an imbalance of autonomic nervous system activity. We used the established Suncus murinus (house musk shrew) model of motion-induced emesis to investigate the effect of horizontal motion on gastric myoelectric activity (recorded using telemetry) and the involvement of the abdominal vagi. Surgical vagotomy increased baseline dysrhythmia and reduced the dominant power of the gastric myoelectric signals. In response to motion, normal gastric myoelectric activity was reduced in sham-operated animals but not in vagotomized animals. Vagotomy, however, failed to affect motion-induced emesis. In conclusion, motion had a differential effect in sham-operated and vagotomized animals, which is consistent with the hypothesis that motion-induced dysrhythmia arises from an autonomic nervous system imbalance.

Mechanisms of burn-induced impairment in gastric slow waves and emptying in rats

Delayed gastric emptying is common following severe large cutaneous burns; however, the mechanisms of burn-induced delayed gastric emptying remain unknown. The aim of this study was to explore the possible involvement of hyperglycemia and cyclooxygenase-2 receptors in the burn-induced gastric dysrhythmias. Gastric slow waves and gastric emptying were assessed in rats 6 h following sham or burn injury. Animals were randomized to one sham-burn and seven burn groups: untreated; two groups of saline treated (control); insulin treated (5 IU/kg); cyclooxygenase-2 inhibitor treated (10 mg/kg); ghrelin treated (2 nmol/rat); and gastric electrical stimulation treated. It was found that 1) severe burn injury impaired gastric slow waves postprandially and delayed gastric emptying; 2) the impairment in gastric slow waves included a decrease in the slow-wave frequency and in the percentage of normal slow waves, and an increase in the percentage of bradygastria (P = 0.001, 0.01, and 0.01, respectively vs. preburn values). None of the gastric slow-wave parameters was significantly correlated with gastric emptying; 3) cyclooxygenase-2 inhibitor normalized burn-induced delayed gastric emptying (P = 0.3 vs. sham-burn), but not gastric dysrhythmias (P < 0.002 vs. sham), whereas insulin normalized both gastric emptying (P = 0.4 vs. sham-burn) and gastric dysrhythmias (P = 0.3 vs. sham-burn); 4) both gastric electrical stimulation and ghrelin accelerated burn-induced delayed gastric emptying (P = 0.002 and 0.04, respectively, vs. untreated burn). In conclusion, hyperglycemia alters gastric slow-wave activity and delayed gastric emptying, while cyclooxygenase-2 inhibition delays gastric emptying without altering gastric slow-wave activity.

Gastric electrical stimulation with long pulses in humans and animals: can data obtained in animals be replicated in humans?

The aim of this study was to investigate and compare effective parameters for gastric electrical stimulation (GES) to modulate gastric muscle functions in different species. Four species: Pigs, dogs, rats, and mice implanted with two pairs of electrodes on the serosal surface of the stomach were studied, respectively. Experiment 1 was designed to entrain/pace gastric slow waves and included a series of 5-min periods with long-pulse GES of different pulse widths and frequencies. Experiment 2 was designed to induce gastric dysrhythmia with long-pulse GES of different frequencies. Gastric slow waves were recorded during the entire experiment. 1) The minimum pulse width for GES to completely entrain the slow waves was similar (100-400 msec) in all four species. 2) With fixed amplitude (4 mA) and pulse width (400 msec), the highest frequency at which slow waves could be paced was similar (about 10-60% higher than the intrinsic slow wave frequency) in all species. 3) With fixed pulse width of 400 msec and amplitude of 6 mA, GES with nine to 18 cycles per min (cpm) was able to induce dysrhythmia in dogs. In addition, there was no significant difference among these frequencies of 9-18 cpm. 4) GES with 400 msec, 6 mA, and 9 cpm was able to induce dysrhythmia in all species. These effective GES parameters in results 1-4 were similar to those used in humans in the literature. There is no significant difference in stimulation parameters when GES is applied to alter gastric slow waves in different animal models. Furthermore, the effective parameters for GES to alter slow waves are similar between the humans and various animal models. These findings suggest that stimulation parameters obtained from animal studies are applicable in humans.

Ameliorating effects and mechanisms of electroacupuncture on gastric dysrhythmia, delayed emptying, and impaired accommodation in diabetic rats

The aim of this study was to investigate the effects and mechanisms of electroacupuncture (EA) on gastric accommodation, gastric dysrhythmia, and gastric emptying (GE) in streptozotocin (STZ)-induced diabetic rats. Five experiments were performed in five groups of STZ-induced diabetic rats to study the effects of EA at ST-36 (Zusanli) on gastric slow-wave dysrhythmia, delayed GE and intestinal transit, impaired gastric accommodation, and the mechanisms of EA involving the autonomic and opioidergic pathways. We found the following: 1) EA improved gastric dysrhythmia in the diabetic rats. The normal percentage of slow waves was 55.4 +/- 2.9% at baseline and significantly increased to 69.2 +/- 2.2% with EA (P = 0.01); this effect was blocked by naloxone. 2) EA resulted in a 21.4% increase in GE and 18.2% increase in small intestinal transit in the diabetic rats. 3) EA restored diabetes-induced impairment in gastric accommodation. Gastric accommodation was 0.98 +/- 0.13 ml with sham EA and significantly increased to 1.21 +/- 0.15 ml with EA (P = 0.01), and this effect was blocked by naloxone. 4) EA increased vagal activity assessed by the spectral analysis of the heart rate variability. We concluded that EA at ST-36 improves gastric dysrhythmia, delayed GE and intestinal transit, and impaired accommodation in STZ-induced diabetic rats, and the improvement seems to be mainly mediated via the vagal pathway. EA may have a promising therapeutic potential for diabetic gastroparesis.

Gastric slow waves, gastrointestinal symptoms and peptides in systemic sclerosis patients

Impaired gastric slow waves, frequent gastrointestinal (GI) symptoms and altered GI peptides have been reported in Scleroderma (SSc) patients. The aim of this study was to investigate the associations among these three important components in GI dysmotility. Seventeen fasted SSc patients underwent four channel surface electrogastrography, measuring % of normal gastric slow waves or dysrhythmia. Patients completed a questionnaire designed by us to assess demographics, upper and lower GI symptoms (symptom presence, frequency and impact on quality of life, QOL), by YES/NO, Likert Scales and Visual Analogue Scales 1-100 mm (called GI Dysmotility Questionnaire, GIDQ) and health-related QOL by SF-36. Fasting plasma vasoactive intestinal peptide (VIP) and motilin levels were measured by peptide immunoassays. There were significant correlations between percentages of gastric dysrhythmias (bradygastria or arrhythmia) and a number of major GI symptoms such as nausea, abdominal bloating and pain. The plasma level of VIP was correlated positively with % dysrhythmia but negatively with % normal slow waves. Motilin was positively correlated with slow wave coupling (coordination). No major differences were noted in the measured peptides or gastric slow waves between limited SSc and diffuse SSc. Correlations were noted between SF-36 domain scores and our GIDQ scores. In SSc patients, gastric dysrhythmias are correlated with certain GI symptoms. Correlations are also noted between plasma VIP/Motilin levels and gastric slow waves. Thus in SSc, gastric dysrhythmias may be predictive of development of certain dyspeptic symptoms. Plasma VIP may be involved in the development of dysrhythmias.

Gastric dysmotility in major depression

Somatic symptoms of the gastrointestinal tract occur frequently in major depressive disorder (MDD) and might be associated with the known autonomic imbalance in the disease. Hence, we have investigated gastric electrical activity in patients suffering from major depression before and after treatment by means of electrogastrography (EGG) to investigate a putative association with either the disease state and its symptoms or its relation to the treatment. EGG readings before and after ingestion of a test meal of 27 patients suffering from major depression were recorded before and after treatment with antidepressants and compared with age-matched controls. Abdominal symptoms were rated by a specific Autonomic Nervous Symptom-score. We found a significantly increased amount of tachygastria before and after medication, indicating increased sympathetic modulation. A significant difference was observed for the instability coefficients before and after medication, indicating gastric dysmotility in our patients prior to treatment. The elevated approximate entropy measure points to increased complexity and dysregulation. Furthermore, we have observed a correlation between subjective sensation of sweating and dry mouth with the sympathetic parameter tachygastria. Our results suggest that major depression is associated with gastric dysrhythmia possibly caused by increased sympathetic modulation. Linear and non-linear EGG measures emphasize a possible role of the autonomic nervous system in the development of gastric symptoms. The treatment with antidepressants seems to increase the activity of the sympathetic nervous system, without aggravating gastric symptoms. The association of increased sympathetic modulation with somatic symptoms was indicated by correlation analysis with these symptoms.

Effects and mechanisms of gastrointestinal electrical stimulation on slow waves: a systematic canine study

The aims of this study were to determine optimal pacing parameters of electrical stimulation on different gut segments and to investigate effects and possible mechanisms of gastrointestinal electrical stimulation on gut slow waves. Twelve female hound-mix dogs were used in this study. A total of six pairs of electrodes were implanted on the stomach, duodenum, and ascending colon. Bilateral truncal vagotomy was performed in six of the dogs. One experiment was designed to study the effects of the pacing frequency on the entrainment of gut slow waves. Another experiment was designed to study the modulatory effects of the vagal and sympathetic pathways on gastrointestinal pacing. The frequency of slow waves was 4.88 +/- 0.23 cpm (range, 4-6 cpm) in the stomach and 19.68 +/- 0.31 cpm (range, 18-22 cpm) in the duodenum. There were no consistent or dominant frequencies of the slow waves in the colon. The optimal parameters to entrain slow waves were: frequency of 1.1 intrinsic frequency (IF; 10% higher than IF) and pulse width of 150-450 ms (mean, 320.0 +/- 85.4 ms) for the stomach, and 1.1 IF and 10-20 ms for the small intestine. Electrical stimulation was not able to alter colon slow waves. The maximum entrainable frequency was 1.27 IF in the stomach and 1.21 IF in the duodenum. Gastrointestinal pacing was not blocked by vagotomy nor the application of an alpha- or beta-adrenergic receptor antagonist; whereas the induction of gastric dysrhythmia with electrical stimulation was completely blocked by the application of the alpha- or beta-adrenergic receptor antagonist. Gastrointestinal pacing is achievable in the stomach and small intestine but not the colon, and the maximal entrainable frequency of the gastric and small intestinal slow waves is about 20% higher than the IF. The entrainment of slow waves with gastrointestinal pacing is not modulated by the vagal or sympathetic pathways, suggesting a purely peripheral or muscle effect.

Gastric myoelectrical differences between Parkinson's disease and multiple system atrophy

The electrogastrogram (EGG) was recorded for 24 hours in 17 Parkinson's disease (PD) patients, 17 multiple system atrophy (MSA) patients, and 8 healthy control subjects to elucidate the differences in the EGG findings between the two diseases. Eight EGG segments (3 preprandial, 3 postprandial, and 2 sleep segments) were selected from the total recording for spectral analysis, from which we obtained the dominant frequency (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. PD patients showed irregular slow waves, high HFR%, and high ICDF, whereas MSA patients showed regular slow waves and low ICDF. Although DF and NFR% increased after meal in controls, postprandial increases in DF and NFR% were less significant in both patient groups compared to the controls. The PD patients presented gastric dysrhythmias indicating gastric pacemaker disturbances. The MSA patients showed regular slow waves with low variability of the slow wave rhythm (low ICDF), which might have resulted from the involvement of gastric autonomic nerve function.

W2051 Electroacupuncture (EA) Improves Impaired Gastric Accommodation, Gastric Dysrhythmia and Delayed Gastric Emptying via the Opioid Pathway in Diabetic Rats Induced By Streptozotocin (STZ)

Introduction: Motor functions of the stomach have traditionally been regarded to differ by stomach region. However, to date there have been few studies on the gastric contractility of the human stomach. Objectives: The aim of the present study was therefore to examine the response to acetylcholine and electrical field stimulation (EFS) of the human fundus, corpus and antrum. Methods: Gastric muscles were obtained from 71 patients (44 males, 27 females with an average age of 60.7 yrs; 34 85 yrs) undergoing gastric cancer surgery. Muscle strips (n = 71) were isolated and attached to a fixed mount and to an isometric strain gauge. The muscle strips were studied In Vitro for their contractile responses to acetylcholine (n=25) and electrical field stimulation (EFS, n=46). N-nitro-L-arginine (L-NA), atropine and tetrodotoxin (TTX) were added to assess the nitro oxide-mediated changes and cholinergic neural pathway involved in EFS-induced contractions. Results: Spontaneous contractile activity was observed in muscle strips of stomach regions. In the antrum, acetylcholine induced increase in contraction frequency and peak contraction in dose dependent pattern, but no significant change was noticed in muscle tone. In corpus and fundus, acetylcholine induced dose-dependent increase in peak contraction and muscle tone, but there was no significant change in frequency. The response to EFS also differed by stomach region. EFS produced no significant change in contractile activity in 22 of 46 muscle strips. When EFS evoked frequency-dependent contraction or relaxation in muscle strips, contraction was primarily observed in the muscle strips from the antrum, and relaxation was primarily observed in the muscle strips of the corpus and fundus. The addition of LNA (100 uM) to the muscle bath converted the EFS-induced relaxation to contractions and increased the EFS-induced contractions. EFS-induced contractions were abolished by atropine (1uM) or TTX (1uM). Conclusions: Our study demonstrated that the response to acetylcholine and electrical field stimulation on human gastric fundus and corpus is different with that of human gastric antrum.

Synchronized gastric electrical stimulation improves vagotomy-induced impairment in gastric accommodation via the nitrergic pathway in dogs

Impaired gastric accommodation and gastric dysrhythmia are common in gastroparesis and functional dyspepsia. Recent studies have shown that synchronized gastric electrical stimulation (SGES) accelerates gastric emptying and enhances antral contractions in dogs. The aim of this study was to investigate the effects and mechanism of SGES on gastric accommodation and slow waves impaired by vagotomy in dogs. Gastric tone, compliance, and accommodation as well as slow waves with and without SGES were assessed in seven female regular dogs and seven dogs with bilateral truncal vagotomy, chronically implanted with gastric serosal electrodes and a gastric cannula. We found that 1) vagotomy impaired gastric accommodation that was normalized by SGES. The postprandial increase in gastric volume was 283.5 +/- 50.6 ml in the controlled dogs, 155.2 +/- 49.2 ml in the vagotomized dogs, and 304.0 +/- 57.8 ml in the vagotomized dogs with SGES. The ameliorating effect of SGES was no longer observed after application of N(omega)-nitro-L-arginine (L-NNA); 2) vagotomy did not alter gastric compliance whereas SGES improved gastric compliance in the vagotomized dogs, and the improvement was also blocked by L-NNA; and 3) vagotomy impaired antral slow wave rhythmicity in both fasting and fed states. SGES at the proximal stomach enhanced the postprandial rhythmicity and amplitude (dominant power) of the gastric slow waves in the antrum. In conclusion, SGES with appropriate parameters restores gastric accommodation and improves gastric slow waves impaired by vagotomy. The improvement in gastric accommodation with SGES is mediated via the nitrergic pathway. Combined with previously reported findings (enhanced antral contractions and accelerated gastric emptying) and findings in this study (improved gastric accommodation and slow waves), SGES may be a viable therapy for gastroparesis.

Cisplatin-Induced Gastric Dysrhythmia and Emesis in Dogs and Possible Role of Gastric Electrical Stimulation

The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation.

T1337 Local Release of Nitric Oxide Restores Gastric Emptying of Solid Food in STZ-Induced Diabetic Rats

G A A b st ra ct s recovery. Then the rats were fed with 1.5ml phenol red solution mixed with methycellulose and EA was performed for 30min immediately after feeding. Gastric retention of phenol red was calculated by the spectrophotometric method. In the control session, no EA was performed. In another study, a gastric balloon was chronically implanted in 5 rats. Gastric accommodationwasmeasured by barostat with ramp distension before and after the induction of diabetes, and with and .without EA at ST36. Results: 1. EA improved gastric dysrhythmia in diabetic rats. The normal percentage of slow wave was 54.7 ± 4.0% at baseline and significantly increased to 68.4 ± 3.6% with EA (P < 0.01) and sustained at 67.8 ± 2.3% during recovery period and 67.1 ± 5.2 after the test meal (P < 0.01). 2. EA resulted in a 21.4% increase in gastric emptying in diabetic rats. Gastric emptying at 30minwas 75.1±5.0% in the control diabetic animals and 91.2±1.5% in the diabetic animals with EA (P=0.01). 3. EA improved impaired gastric accommodation. The confirmed diabetic rats showed a significantly decreased gastric accommodation (0.85 ± 0.14ml with diabetes vs. 0.69 ± 0.12ml before STZ injection, P = 0.05). EA at ST36 resulted in a striking effect on gastric accommodation with a mean increase of 87.8 ± 25.8% (P < 0.05). 4. EA significantly increased vagal activity and sympathovagal balance in diabetic rats. The high frequency (vagal component) was 0.55±0.05 at baseline and increased to 0.61 ± 0.03 during EA (P = 0.03); the LF/HF (sympathovagal balance) was 0.85 ± 0.13 at baseline and significantly decreased to 0.67 ± 0.08 during EA. Conclusion: EA at ST 36 improves impaired gastric accommodation, gastric dysrhythmia and delayed gastric emptying and the improvement may be mediated via the vagal pathway. EA may have a promising therapeutic potential for diabetic gastroparesis.

T1359 Prostaglandin EP 3 Receptor-Mediated Disruption of Gastric Slow Wave Rhythm and Coupling Measured By Multichannel Mucosal Mapping in An In Vivo Canine Model

Background: Prostaglandin synthesis inhibitors (e.g. indomethacin) prevent gastric slow wave dysrhythmias in humanmodels, showing endogenous prostaglandins disrupt slowwave cycling. In isolated tissues, prostaglandin EP3 agonists elicit slow wave rhythm disturbances. Prostaglandin infusion evokes dysrhythmias in an In Vivo canine model, but roles of different EP receptors are unexplored. Regional differences in actions of EP agonists on In Vivo slow waves are unknown. Aims: (i) To compare dose-dependent effects of intravenous prostaglandin E2 (PGE2), butaprost (EP2 agonist), and sulprostone (EP3 agonist) on slow wave rhythm and coupling In Vivo and (ii) to contrast regional responses of the corpus to the antrum. Methods: 6 female dogs (18-25 kg) underwent slow wave mapping on separate days under 3 conditions (PGE2, butaprost, and sulprostone). After overnight fasting, endoscopy was performed with midazolam and ketamine and a catheter with 3 bipolar electrodes was affixed to the mucosa using endoclips 2, 7 and 17 cm from the pylorus. Multichannel recordings were obtained x 30 min under control conditions, and with low, medium, and high dose infusions of the test agents. Slow wave parameters at each recording site were % time in normal frequency (3.7-6.3 cycles per min[cpm]), bradygastria ( 6.3 cpm). Corpus-antrum coupling was calculated by commercial software (AcqKnowledge). Results: In control recordings, % time in normal rhythm was 61±7% proximally, 58±10% in the middle lead, and 84±3% distally. Corpus-antrum coupling was 78±4%. Low-dose PGE2 (35 μg/kg/h) reduced time in normal rhythm to 64±14% (P=0.05) and increased time in bradygastria from 9±2 to 22±6% (P=0.02) distally but did not induce tachygastria and had no effect on normal rhythm (61±4%) proximally. Coupling decreased to 69±5% with PGE2 (P=0.01). Higher PGE2 doses did not have additional effect. Mediumdose sulprostone (0.15 μg/kg/min) reduced normal rhythm to 60±7% (P=0.01) and increased bradygastria to 18±2% (P=0.01) distally but did not alter proximal normal rhythm (70.3+11.4%). High dose sulprostone (0.5 μg/kg/min) decreased coupling to 72±7% (P= 0.02). High-dose butaprost (0.5 μg/kg/min) did not affect distal (71±14%) or proximal (60±13%) normal rhythm or coupling (77±15%). Conclusions: Prostaglandin E2 promotes loss of normal slow wave rhythm in an In Vivo canine model with induction of bradygastria and uncoupling that are restricted to the antrum. These effects are mimicked by the EP3 agonist sulprostone but not the EP2 agonist butaprost. Thus as in excised tissues, prominent slow wave disruption is observed with EP3 receptor agonism in whole animals.

T1076 Drug-Induced Gastric Dysrhythmia and Emesis in Dogs and Possible Roles of Gastric Electrical Stimulation

T1076 Drug-Induced Gastric Dysrhythmia and Emesis in Dogs and Possible Roles of Gastric Electrical Stimulation

Interstitial cells of Cajal in diabetic gastroenteropathy

Gastroenteropathy causes considerable morbidity in patients with diabetes mellitus and represents a major healthcare burden. Current treatments are largely symptomatic and frequently ineffective. Development of new therapeutic options is hampered by poor understanding of the underlying pathomechanisms. Experimental studies and sparse human data indicate that diabetic gastroenteropathy is multifactorial and involves not only parasympathetic and sympathetic autonomic nerves, but also enteric neurons, smooth muscle cells and interstitial cells of Cajal (ICC). ICC are mesenchymal cells that occur throughout the muscular coat of the gastrointestinal tract and provide functions critical for normal gastrointestinal motility including generation and propagation of electrical slow waves and mediation of bidirectional communication between the autonomic nervous system and smooth muscle cells. Through these functions, and in concert with other cell types of the gastrointestinal muscles, ICC support basic gastrointestinal functions such as digestion, absorption and waste removal. Loss or dysfunction of ICC in various dysmotilities and their animal models has been shown to lead to gastric dysrhythmias, gastroparesis, slow intestinal transit, impaired neuroeffector mechanisms and altered visceral afferent signalling that are considered hallmarks of diabetic gastroenteropathy. These findings and an increasing body of evidence indicating disruptions of ICC networks in diabetes suggest that the loss of ICC in this disorder is probably of functional significance and could even be a major pathogenetic factor. Future research should focus on the identification of the molecular and cellular mechanisms underlying ICC loss in diabetes and the translation of the experimental findings into treatments.

A novel method of 2-channel dual-pulse gastric electrical stimulation improves solid gastric emptying in dogs

Gastric electrical stimulation (GES) is known to improve vomiting with short pulses, normalize dysrhythmia with long pulses, and accelerate gastric emptying with 2 channels. The aim of this study was to assess the effects of a new method GES, namely, 2-channel GES with dual pulses on gastric emptying of solids as well as gastric dysrhythmia and emetic responses. Seven beagle dogs implanted with 4 pairs of electrodes were studied. A novel method of GES was proposed: 2-channel dual-pulse GES in which each stimulus was composed of a short pulse followed with a long pulse, and stimulation was delivered at 2 different locations. The study was performed to test the effects of this new method of GES on vasopressin-induced delayed gastric emptying of solids, gastric dysrhythmia, and emetic responses. (1) Vasopressin-induced gastric dysrhythmia and emetic responses, as well as delayed gastric emptying of solids (P < .01). (2) Two-channel, but not 1-channel, dual-pulse GES was able to accelerate vasopressin-induced delayed gastric emptying of solids. (3) Both 1- and 2-channel dual-pulse GES was capable of improving dysrhythmia and emetic responses (P < .01). The novel method of 2-channel dual-pulse GES is capable of accelerating gastric emptying of solids and improving dysrhythmia and emetic responses induced by vasopressin. This new method of GES may have a potential for gastroparesis.

Clinical application prospects of gastric pacing for treating postoperative gastric motility disorders

Similar to the heartbeat, gastric peristalsis is regulated by an electrical rhythm generated by a pacemaker. Thus, electrical dysrhythmia of gastric slow waves will inevitably affect gastric peristalsis and emptying. The recurrence of postoperative gastroparesis is thereby closely related to the abnormalities of electrical dysrhythmia and ectopic pacemakers, resulting in postoperatively persistent gastric motility disorders in some severe cases, despite the use of prokinetic and antiemetic drugs. Recent studies have demonstrated that gastric pacing, analogous to pacing the human heart, is an attractive and promising therapy that is both feasible and safe. Gastric pacing has been shown to be strikingly effective in normalizing gastric dysrhythmia, increasing the activity of the gastric slow wave and thereby prompting gastric dynamia and emptying. Furthermore, the long-term utilization of gastric pacing can (i) relieve patients from clinical symptoms, such as nausea and vomiting; (ii) release patients with severe postoperative gastroparesis from relying on prokinetic drugs and the jejunal feeding tube; (iii) return patients to normal oral nutritional intake and provide a more satisfactory nutritional status and most importantly; and (iv) give patients a better quality of life. Overall, research focused on gastric pacing has demonstrated excellent prospects for clinical application in the treatment of postoperative gastroparesis disorders, especially for those unresponsive to prokinetic drugs.