High-energy pacing inhibits slow-wave dysrhythmias in the small intestine.

The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.

Mapping the rat gastric slow wave conduction pathway: Bridging in vitro and in vivo methods, revealing a loosely-coupled region in the distal stomach.

Rhythmic electrical events, termed slow waves, govern the timing and amplitude of phasic contractions of the gastric musculature. Extracellular multielectrode measurement of gastric slow waves can be a biomarker for phenotypes of motility dysfunction. However, a gastric slow wave conduction pathway for the rat, a common animal model, is unestablished. In this study, the validity of extracellular recording was demonstrated in vitro with simultaneous intracellular and extracellular recordings and by pharmacological inhibition of slow waves. The conduction pathway was determined by in vivo extracellular recordings while considering the effect of motion. Slow wave characteristics (mean (SD)) varied regionally, having higher amplitude in the antrum than the distal corpus (1.03 (0.12) mV vs 0.75 (0.31) mV; n = 7; p = 0.025 paired t-test) and faster propagation near the greater curvature than the lesser curvature (1.00 (0.14) mm s-1 vs 0.74 (0.14) mm s-1; n = 9 GC, 7 LC; p = 0.003 unpaired t-test). Notably, in some subjects, separate wavefronts propagated near the lesser and greater curvatures with a loosely-coupled region occurring in the area near the distal corpus midline, at the interface of the two wavefronts. This region had either the greater or lesser curvature wavefront propagating through it in a time-varying manner. The conduction pattern suggests that slow waves in the rat stomach form annular wavefronts in the antrum and not the corpus. This study has implications for interpretation of the relationship between slow waves, the interstitial cells of Cajal network structure, smooth muscles, and gastric motility.

Smart capsules for sensing and sampling the gut: status, challenges and prospects.

Smart capsules are developing at a tremendous pace with a promise to become effective clinical tools for the diagnosis and monitoring of gut health. This field emerged in the early 2000s with a successful translation of an endoscopic capsule from laboratory prototype to a commercially viable clinical device. Recently, this field has accelerated and expanded into various domains beyond imaging, including the measurement of gut physiological parameters such as temperature, pH, pressure and gas sensing, and the development of sampling devices for better insight into gut health. In this review, the status of smart capsules for sensing gut parameters is presented to provide a broad picture of these state-of-the-art devices while focusing on the technical and clinical challenges the devices need to overcome to realise their value in clinical settings. Smart capsules are developed to perform sensing operations throughout the length of the gut to better understand the body's response under various conditions. Furthermore, the prospects of such sensing devices are discussed that might help readers, especially health practitioners, to adapt to this inevitable transformation in healthcare. As a compliment to gut sensing smart capsules, significant amount of effort has been put into the development of robotic capsules to collect tissue biopsy and gut microbiota samples to perform in-depth analysis after capsule retrieval which will be a game changer for gut health diagnosis, and this advancement is also covered in this review. The expansion of smart capsules to robotic capsules for gut microbiota collection has opened new avenues for research with a great promise to revolutionise human health diagnosis, monitoring and intervention.

Spatial response of jejunal pacing defined by a novel high-resolution multielectrode array.

Gastric pacing has shown preclinical success in modulating bioelectrical slow-wave activity and has potential as a novel therapy for functional motility disorders. However, the translation of pacing techniques to the small intestine remains preliminary. This paper presents the first high-resolution framework for simultaneous pacing and response mapping of the small intestine. A novel surface-contact electrode array, capable of simultaneous pacing and high-resolution mapping of the pacing response, was developed and applied in vivo on the proximal jejunum of pigs. Pacing parameters including the input energy and pacing electrode orientation were systematically evaluated, and the efficacy of pacing was determined by analyzing spatiotemporal characteristics of entrained slow waves. Histological analysis was conducted to determine if the pacing resulted in tissue damage. A total of 54 studies were conducted on 11 pigs, and pacemaker propagation patterns were successfully achieved at both low (2 mA, 50 ms) and high (4 mA, 100 ms) energy levels with the pacing electrodes oriented in the antegrade, retrograde, and circumferential directions. The high energy level performed significantly better (P = 0.014) in achieving spatial entrainment. Comparable success (greater than 70%) was achieved when pacing in the circumferential and antegrade pacing directions, and no tissue damage was observed at the pacing sites. This study defined the spatial response of small intestine pacing in vivo revealing effective pacing parameters for slow-wave entrainment in the jejunum. Intestinal pacing now awaits translation to restore disordered slow-wave activity associated with motility disorders.NEW & NOTEWORTHY A novel surface-contact electrode array customized for the small intestine anatomy enabled simultaneous pacing and high-resolution response mapping. The spatial response of small intestine bioelectrical activity to pacing was mapped for the first time in vivo. Antegrade and circumferential pacing achieved spatial entrainment over 70% of the time and their induced pattern was held for 4-6 cycles postpacing at high energy (4 mA, 100 ms, at ∼2.7 s which corresponds to 1.1 × intrinsic frequency).

The bioelectrical conduction system around the ileocecal junction defined through in vivo high-resolution mapping in rabbits.

Coordinated contractions across the small and large intestines via the ileocecal junction (ICJ) are critical to healthy gastrointestinal function and are in part governed by myoelectrical activity. In this study, the spatiotemporal characteristics of the bioelectrical conduction across the ICJ and its adjacent regions were quantified in anesthetized rabbits. High-resolution mapping was applied from the terminal ileum (TI) to the sacculus rotundus (SR), across the ICJ and into the beginning of the large intestine at the cecum ampulla coli (AC). Orally propagating slow wave patterns in the SR did not entrain the TI. However, aborally propagating patterns from the TI were able to entrain the SR. Bioelectrical activity was recorded within the ICJ and AC, revealing complex interactions of slow waves, spike bursts, and bioelectrical quiescence. This suggests the involvement of myogenic coordination when regulating motility between the small and large intestines. Mean slow wave frequency between regions did not vary significantly (13.74-17.16 cycles/min). Slow waves in the SR propagated with significantly faster speeds (18.51 ± 1.57 mm/s) compared with the TI (14.05 ± 2.53 mm/s, P = 0.0113) and AC (9.56 ± 1.56 mm/s, P = 0.0001). Significantly higher amplitudes were observed in both the TI (0.28 ± 0.13 mV, P = 0.0167) and SR (0.24 ± 0.08 mV, P = 0.0159) within the small intestine compared with the large intestine AC (0.03 ± 0.01 mV). We hypothesize that orally propagating slow waves facilitate a motor-brake pattern in the SR to limit outflow into the ICJ, similar to those previously observed in other gastrointestinal regions.NEW & NOTEWORTHY Competing slow wave pacemakers were observed in the terminal ileum and sacculus rotundus. Prevalent oral propagation in the sacculus rotundus toward the terminal ileum potentially acts as a brake mechanism limiting outflow. Slow waves and periods of quiescence at the ileocecal junction suggest that activation may depend on the coregulatory flow and distention pathways. Slow waves and spike bursts in the cecum impart a role in the coordination of motility.

Targeted ablation of gastric pacemaker sites to modulate patterns of bioelectrical slow wave activation and propagation in an anesthetized pig model.

Gastric motility is coordinated by underlying bioelectrical slow waves. Gastric dysrhythmias occur in gastrointestinal (GI) motility disorders, but there are no validated methods for eliminating dysrhythmias. We hypothesized that targeted ablation could eliminate pacemaker sites in the stomach, including dysrhythmic ectopic pacemaker sites. In vivo high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to localize normal and ectopic gastric pacemaker sites in 13 anesthetized pigs. Radiofrequency ablation was performed in a square formation surrounding the pacemaker site. Postablation high-resolution mapping revealed that ablation successfully induced localized conduction blocks after 18 min (SD 5). Normal gastric pacemaker sites were eliminated by ablation (n = 6), resulting in the emergence of a new pacemaker site immediately distal to the original site in all cases. Ectopic pacemaker sites were similarly eliminated by ablation in all cases (n = 7), and the surrounding mapped area was then entrained by normal antegrade activity in five of those cases. Histological analysis showed that ablation lesions extended through the entire depth of the muscle layer. Immunohistochemical staining confirmed localized interruption of the interstitial cell of Cajal (ICC) network through the ablation lesions. This study demonstrates that targeted gastric ablation can effectively modulate gastric electrical activation, including eliminating ectopic sites of slow wave activation underlying gastric dysrhythmias, without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.NEW & NOTEWORTHY This study presents gastric ablation as a novel tool for modulating gastric bioelectrical activation, including eliminating the normal gastric pacemaker site as well as abnormal ectopic pacemaker sites underlying gastric dysrhythmias. Targeted application of radiofrequency ablation was able to eliminate these pacemaker sites without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.

Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

Localized gastric distension disrupts slow-wave entrainment leading to temporary ectopic propagation: a high-resolution electrical mapping study.

Gastric distension is known to affect normal slow-wave activity and gastric function, but links between slow-wave dysrhythmias and stomach function are poorly understood. Low-resolution mapping is unable to capture complex spatial properties of gastric dysrhythmias, necessitating the use of high-resolution mapping techniques. Characterizing the nature of these dysrhythmias has implications in the understanding of postprandial function and the development of new mapping devices. In this two-phase study, we developed and implemented a protocol for measuring electrophysiological responses to gastric distension in porcine experiments. In vivo, serosal high-resolution electrical mapping (256 electrodes; 36 cm2) was performed in anaesthetized pigs (n = 11), and slow-wave pattern, velocity, frequency, and amplitude were quantified before, during, and after intragastric distension. Phase I experiments (n = 6) focused on developing and refining the distension mapping methods using a surgically inserted intragastric balloon, with a variety of balloon types and distension protocols. Phase II experiments (n = 5) used barostat-controlled 500-mL isovolumetric distensions of an endoscopically introduced intragastric balloon. Dysrhythmias were consistently induced in all five gastric distensions, using refined distension protocols. Dysrhythmias appeared 23 s (SD = 5 s) after the distension and lasted 129 s (SD = 72 s), which consisted of ectopic propagation originating from the greater curvature in the region of distension. In summary, our results suggest that distension disrupts gastric entrainment, inducing temporary ectopic slow-wave propagation. These results may influence the understanding of the postprandial stomach and electrophysiological effects of gastric interventions.NEW & NOTEWORTHY This study presents the discovery of temporary dysrhythmic ectopic pacemakers in the distal stomach caused by localized gastric distension. Distension-induced dysrhythmias are an interesting physiological phenomenon that can inform the design of new interventional and electrophysiological protocols for both research and the clinic. The observation of distension-induced dysrhythmias also contributes to our understanding of stretch-sensitivity in the gut and may play an important role in normal and abnormal postprandial physiology.

Gastric ablation as a novel technique for modulating electrical conduction in the in vivo stomach.

Gastric motility is coordinated by underlying bioelectrical "slow wave" activity. Slow wave dysrhythmias are associated with motility disorders, including gastroparesis, offering an underexplored potential therapeutic target. Although ablation is widely used to treat cardiac arrhythmias, this approach has not yet been trialed for gastric electrical abnormalities. We hypothesized that ablation can create localized conduction blocks and modulate slow wave activation. Radiofrequency ablation was performed on the porcine serosa in vivo, encompassing a range of parameters (55-85°C, adjacent points forming a line, 5-10 s/point). High-resolution electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to define baseline and acute postablation activation patterns. Tissue damage was evaluated by hematoxylin and eosin and c-Kit stains. Results demonstrated that RF ablation successfully induced complete conduction block and a full thickness lesion in the muscle layer at energy doses of 65-75°C for 5-10 s/point. Gastric ablation may hold therapeutic potential for gastric electrical abnormalities in the future.NEW & NOTEWORTHY This study presents gastric ablation as a new method for modulating slow wave activation and propagation in vivo, by creating localized electrical conduction blocks in the stomach, validated by high-resolution electrical mapping and histological tissue analysis. The results define the effective energy dose range for creating conduction blocks, while maintaining the mucosal and submucosal integrity, and demonstrate the electrophysiological effects of ablation. In future, gastric ablation can now be translated toward disrupting dysrhythmic slow wave activation.

Slow-wave coupling across a gastroduodenal anastomosis as a mechanism for postsurgical gastric dysfunction: evidence for a "gastrointestinal aberrant pathway".

Postsurgical gastric dysfunction is common, but the mechanisms are varied and poorly understood. The pylorus normally acts as an electrical barrier isolating gastric and intestinal slow waves. In this report, we present an aberrant electrical conduction pathway arising between the stomach and small intestine, following pyloric excision and surgical anastomosis, as a novel disease mechanism. A patient was referred with postsurgical gastroparesis following antrectomy, gastroduodenostomy, and vagotomy for peptic ulceration. Scintigraphy confirmed markedly abnormal 4-h gastric retention. Symptoms included nausea, vomiting, postprandial distress, and reflux. Intraoperative, high-resolution electrical mapping was performed across the anastomosis immediately before revision gastrectomy, and the resected anastomosis underwent immunohistochemistry for interstitial cells of Cajal. Mapping revealed continuous, stable abnormal retrograde slow-wave propagation through the anastomosis, with slow conduction occurring at the scar (4.0 ± 0.1 cycles/min; 2.5 ± 0.6 mm/s; 0.26 ± 0.15 mV). Stable abnormal retrograde propagation continued into the gastric corpus with tachygastria (3.9 ± 0.2 cycles/min; 1.6 ± 0.5 mm/s; 0.19 ± 0.12 mV). Histology confirmed ingrowth of atypical ICC through the scar, defining an aberrant pathway enabling transanastomotic electrical conduction. In conclusion, a "gastrointestinal aberrant pathway" is presented as a novel proposed cause of postsurgical gastric dysfunction. The importance of aberrant anastomotic conduction in acute and long-term surgical recovery warrants further investigation.NEW & NOTEWORTHY High-resolution gastric electrical mapping was performed during revisional surgery in a patient with severe gastric dysfunction following antrectomy and gastroduodenostomy. The results revealed continuous propagation of slow waves from the duodenum to the stomach, through the old anastomotic scar, and resulting in retrograde-propagating tachygastria. Histology showed atypical interstitial cells of Cajal growth through the anastomotic scar. Based on these results, we propose a "gastrointestinal aberrant pathway" as a mechanism for postsurgical gastric dysfunction.

The Effect of Gastric Electrical Stimulation on Small Bowel Motility in Patients With Gastroparesis and Concomitant Pancreatic and Small Bowel Dysfunction: From Animal Model to Human Application.

BACKGROUND/AIMS: Patients with gastroparesis often have biliary/pancreatic and small bowel symptoms but the effects of gastric electrical stimulation on small bowel electrical activity of the mid-gut have not been studied. Animal model aim: Establish gastric and upper small bowel/biliary slow wave activity relationships with electrical stimulation. Human study aim: Demonstrate improvement in symptoms associated with proximal small bowel dysmotility in gastric stimulated patients. MATERIALS AND METHODS: Animal model: In vivo evoked responses of duodenal and Sphincter of Oddi measures recorded during gastric electrical stimulation in a nonsurvival swine model (N = 3). High-resolution electrical slow wave mapping of frequency, amplitude, and their ratio, for duodenal and Sphincter of Oddi electrical activity were recorded. Human study: Patients (N = 8) underwent temporary gastric stimulation with small bowel electrodes. Subjective and objective data was collected before and after temporary gastric stimulation. Symptom scores, gastric emptying times, and mucosal electrograms via low-resolution mapping were recorded. RESULTS: Animal gastric stimulation resulted in some changes in electrical activity parameters, especially with the highest energies delivered but the changes were not statistically significant. Human study revealed improvement in symptom and illness severity scores, and changes in small bowel mucosal slow wave activity. CONCLUSIONS: Gastric electrical stimulation in an animal model seems to show nonsignificant effects small bowel slow wave activity and myoelectric signaling, suggesting the existence of intrinsic neural connections. Human data shows more significance, with possible potential for therapeutic use of electrical stimulation in patients with gastroparesis and pancreato-biliary and small bowel symptoms of the mid-gut. This study was limited by the nonsurvival pig model, small sample size, and open label human study.

High-resolution anatomic correlation of cyclic motor patterns in the human colon: Evidence of a rectosigmoid brake.

Colonic cyclic motor patterns (CMPs) have been hypothesized to act as a brake to limit rectal filling. However, the spatiotemporal profile of CMPs, including anatomic origins and distributions, remains unclear. This study characterized colonic CMPs using high-resolution (HR) manometry (72 sensors, 1-cm resolution) and their relationship with proximal antegrade propagating events. Nine healthy volunteers were recruited. Recordings were performed over 4 h, with a 700-kcal meal given after 2 h. Propagating events were visually identified and analyzed by pattern, origin, amplitude, extent of propagation, velocity, and duration. Manometric data were normalized using anatomic landmarks identified on abdominal radiographs. These were mapped over a three-dimensional anatomic model. CMPs comprised a majority of detected propagating events. Most occurred postprandially and were retrograde propagating events (84.9 ± 26.0 retrograde vs. 14.3 ± 11.8 antegrade events/2 h, P = 0.004). The dominant sites of initiation for retrograde CMPs were in the rectosigmoid region, with patterns proximally propagating by a mean distance of 12.4 ± 0.3 cm. There were significant differences in the characteristics of CMPs depending on the direction of travel and site of initiation. Association analysis showed that proximal antegrade propagating events occurred independently of CMPs. This study accurately characterized CMPs with anatomic correlation. CMPs were unlikely to be triggered by proximal antegrade propagating events in our study context. However, the distal origin and prominence of retrograde CMPs could still act as a mechanism to limit rectal filling and support the theory of a "rectosigmoid brake."NEW & NOTEWORTHY Retrograde cyclic motor patterns (CMPs) are the dominant motor patterns in a healthy prepared human colon. The major sites of initiation are in the rectosigmoid region, with retrograde propagation, supporting the idea of a "rectosigmoid brake." A significant increase in the number of CMPs is seen after a meal. In our study context, the majority of CMPs occurred independent of proximal propagating events, suggesting that CMPs are primarily controlled by external innervation.

A theoretical analysis of anatomical and functional intestinal slow wave re-entry.

Intestinal bioelectrical slow waves are a key regulator of intestinal motility. Peripheral pacemakers, ectopic initiations and sustained periods of re-entrant activities have all been experimentally observed to be important factors in setting the frequency of intestinal slow waves, but the tissue-level mechanisms underpinning these activities are unclear. This theoretical analysis aimed to define the initiation, maintenance, and termination criteria of two classes of intestinal re-entrant activities: anatomical re-entry and functional re-entry. Anatomical re-entry was modeled in a three-dimensional (3D) cylindrical model, and functional rotor was modeled in a 2D rectangle model. A single-pulse stimulus was used to invoke an anatomical re-entry and a prolonged refractory block was used to invoke the rotor. In both cases, the simulated re-entrant activities operated at frequencies above the baseline entrainment frequency. The anatomical re-entry simulation results demonstrated that a temporary functional refractory block would be required to initiate the re-entrant activity in a single direction around the cylindrical model. The rotor could be terminated by a single-pulse stimulus delivered around the core of the rotor. In conclusion, the simulation results provide the following new insights into the mechanisms of intestinal re-entry: (i) anatomical re-entry is only maintained within a specific range of velocities, outside of which the re-entrant activities become either an ectopic activity or simultaneous activations of the intestinal wall; (ii) a maintained rotor entrained slow waves faster in the antegrade direction than in the retrograde direction. Simulations are shown to be a valuable tool for achieving novel insights into the mechanisms of intestinal slow wave dysrhythmia.

A novel retractable laparoscopic device for mapping gastrointestinal slow wave propagation patterns.

BACKGROUND: Gastric slow waves regulate peristalsis, and gastric dysrhythmias have been implicated in functional motility disorders. To accurately define slow wave patterns, it is currently necessary to collect high-resolution serosal recordings during open surgery. We therefore developed a novel gastric slow wave mapping device for use during laparoscopic procedures. METHODS: The device consists of a retractable catheter constructed of a flexible nitinol core coated with Pebax. Once deployed through a 5-mm laparoscopic port, the spiral head is revealed with 32 electrodes at 5 mm intervals. Recordings were validated against a reference electrode array in pigs and tested in a human patient. RESULTS: Recordings from the device and a reference array in pigs were identical in frequency (2.6 cycles per minute; p = 0.91), and activation patterns and velocities were consistent (8.9 ± 0.2 vs 8.7 ± 0.1 mm s-1; p = 0.2). Device and reference amplitudes were comparable (1.3 ± 0.1 vs 1.4 ± 0.1 mV; p = 0.4), though the device signal-to-noise ratio was higher (17.5 ± 0.6 vs 12.8 ± 0.6 dB; P < 0.0001). In the human patient, corpus slow waves were recorded and mapped (frequency 2.7 ± 0.03 cycles per minute, amplitude 0.8 ± 0.4 mV, velocity 2.3 ± 0.9 mm s-1). CONCLUSION: In conclusion, the novel laparoscopic device achieves high-quality serosal slow wave recordings. It can be used for laparoscopic diagnostic studies to document slow wave patterns in patients with gastric motility disorders.

Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.

High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm2) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 ± 0.1 mV to 2.5 ± 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration.

Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting.

BACKGROUND & AIMS: Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, therefore the diseases may share pathophysiologic features. We investigated this hypothesis by quantifying densities of interstitial cells of Cajal (ICCs) and mapping slow-wave abnormalities in patients with CUNV vs controls. METHODS: Clinical data and gastric biopsy specimens were collected from 9 consecutive patients with at least 6 months of continuous symptoms of CUNV but normal gastric emptying who were treated at the University of Mississippi Medical Center, and from 9 controls (individuals free of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural analyses were performed on tissue samples. Slow-wave propagation profiles were defined by high-resolution electrical mapping (256 electrodes; 36 cm(2)). Results from patients with CUNV were compared with those of controls as well as patients with gastroparesis who were studied previously by identical methods. RESULTS: Patients with CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field, respectively; P < .05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1 of 9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wavefront collisions, conduction blocks, and re-entry), operating across bradygastric, normal (range, 2.4-3.7 cycles/min), and tachygastric frequencies; dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal vs 7.6 mm/s circumferential; P < .01). ICCs were less depleted in patients with CUNV than in those with gastroparesis (mean, 3.5 vs 2.3 bodies/field, respectively; P < .05), but slow-wave dysrhythmias were similar between groups. CONCLUSIONS: This study defined cellular and bioelectrical abnormalities in patients with CUNV, including the identification of slow-wave re-entry. Pathophysiologic features of CUNV were observed to be similar to those of gastroparesis, indicating that they could be spectra of the same disorder. These findings offer new insights into the pathogenesis of CUNV and may help to inform future treatments.

Simultaneous anterior and posterior serosal mapping of gastric slow-wave dysrhythmias induced by vasopressin.

NEW FINDINGS: What is the central question of this study? This study aimed to provide the first comparison of simultaneous high-resolution mapping of anterior and posterior gastric serosa over sustained periods. What is the main finding and its importance? Episodes of spontaneous gastric slow-wave dysrhythmias increased significantly following intravenous infusion of vasopressin compared with the baseline state. A number of persistent dysrhythmias were defined, including ectopic activation, conduction block, rotor, retrograde and collision/merger of wavefronts. Slow-wave dysrhythmias could occur either simultaneously or independently on the anterior and posterior gastric serosa, and interacted depending on activation-repolarization and frequency dynamics. High-resolution mapping enables mechanistic insights into gastric slow-wave dysrhythmias and is now achieving clinical translation. However, previous studies have focused mainly on dysrhythmias occurring on the anterior gastric wall. The present study simultaneously mapped the anterior and posterior gastric serosa during episodes of dysrhythmias induced by vasopressin to aid understanding of dysrhythmia initiation, maintenance and termination. High-resolution mapping (8 × 16 electrodes on each serosa; 20-74 cm2 ) was performed in anaesthetized dogs. Baseline recordings (21 ± 8 min) were followed by intravenous infusion of vasopressin (0.1-0.5 IU ml-1 at 60-190 ml h-1 ) and further recordings (22 ± 13 min). Slow-wave activation maps, amplitudes, velocity, interval and frequency were calculated, and differences compared between baseline and postinfusion. All dogs demonstrated an increased prevalence of dysrhythmic events following infusion of vasopressin (17 versus 51%). Both amplitude and velocity demonstrated significant differences (baseline versus postinfusion: 3.6 versus 2.2 mV; 7.7 versus 6.5 mm s-1 ; P < 0.05 for both). Dysrhythmias occurred simultaneously or independently on the anterior and posterior serosa, and then interacted according to frequency dynamics. A number of persistent dysrhythmias were compared, including the following: ectopic activation (n = 2 animals), conduction block (n = 1), rotor (n = 2), retrograde (n = 3) and collision/merger of wavefronts (n = 2). We conclude that infusion of vasopressin induces gastric dysrhythmias, which occur across a heterogeneous range of frequencies and patterns. The results demonstrate that different classes of gastric dysrhythmias may arise simultaneously or independently in one or both surfaces of the serosa, then interact according to their relative frequencies. These results will help to inform interpretation of clinical dysrhythmia.

Acute Slow Wave Responses to High-Frequency Gastric Electrical Stimulation in Patients With Gastroparesis Defined by High-Resolution Mapping.

BACKGROUND AND AIMS: High-frequency gastric electrical stimulation (GES) has emerged as a therapy for gastroparesis, but the mechanism(s) of action remain unclear. There is a need to refine stimulation protocols for clinical benefit, but a lack of accurate techniques for assessing mechanisms in clinical trials, such as slow wave modulation, has hindered progress. We thereby aimed to assess acute slow wave responses to GES in gastroparesis patients using high-resolution (HR) (multi-electrode) mapping, across a range of stimulation doses achievable by the Enterra stimulation device (Medtronic Inc., MN, USA). MATERIALS AND METHODS: Patients with medically refractory gastroparesis (n = 8) undergoing device implantation underwent intraoperative HR mapping (256 electrodes). Baseline recordings were followed by four protocols of increasing stimulation intensity, with washout periods. Slow wave patterns, frequency, velocity, amplitude, and dysrhythmia rates were quantified by investigators blinded to stimulation settings. RESULTS: There was no difference in slow wave pattern, frequency, velocity, or amplitude between baseline, washout, and stimulation periods (all p > 0.5). Dysrhythmias included ectopic pacemakers, conduction blocks, retrograde propagation, and colliding wavefronts, and dysrhythmia rates were unchanged with stimulation off vs. on (31% vs. 36% duration dysrhythmic; p > 0.5). Symptom scores and gastric emptying were improved at 5.8 month follow-up (p < 0.05). CONCLUSIONS: High-frequency GES protocols achievable from a current commercial device did not acutely modulate slow wave activity or dysrhythmias. This study advances clinical methods for identifying and assessing therapeutic GES parameters, and can be applied in future studies on higher-energy protocols and devices.