Background & Aims Interstitial cells of Cajal (ICC) generate slow waves. Disrupted ICC networks and gastric dysrhythmias are each associated with gastroparesis. However, there are no data on the initiation and propagation of slow waves in gastroparesis, because research tools have lacked spatial resolution. We applied high-resolution electrical mapping to quantify and classify gastroparesis slow-wave abnormalities in spatiotemporal detail. Methods Serosal HR mapping was performed, using flexible arrays (256 electrodes; 36 cm2), at stimulator implantation in 12 patients with diabetic or idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and amplitude field mapping, and propagation animation. ICC numbers were determined from gastric biopsies. Results Mean ICC counts were reduced in patients with gastroparesis (2.3 vs 5.4 bodies/field; P<.001). Slow-wave abnormalities were detected by HR mapping in 11/12 patients. Several new patterns were observed and classified as ‘abnormal initiation’ (10/12; stable ectopic pacemakers or diffuse focal events; median 3.3 c/min, range 2.1-5.7), or ‘abnormal conduction’ (7/10; reduced velocities or conduction blocks; median 2.9 c/min; range 2.1-3.6). Circumferential conduction emerged during aberrant initiation or incomplete block and was associated with velocity elevation (7.3 vs 2.9 mm s−1; P=.002) and increased amplitudes beyond a low base value (415 vs 170 μV; P=.002). Conclusions HR mapping revealed new categories of abnormal human slow-wave activity. Abnormalities of slow-wave initiation and conduction occur in gastroparesis, often at normal frequency, which could be missed by tests that lack spatial resolution. Irregular initiation, aberrant conduction, and low amplitude activity could contribute to the pathogenesis of gastroparesis.

Slow waves coordinate gastric motility, and abnormal slow-wave activity is thought to contribute to motility disorders. The current understanding of normal human gastric slow-wave activity is based on extrapolation from data derived from sparse electrode recordings and is therefore potentially incomplete. This study employed high-resolution (HR) mapping to reevaluate human gastric slow-wave activity. HR mapping was performed in 12 patients with normal stomachs undergoing upper abdominal surgery, using flexible printed circuit board (PCB) arrays (interelectrode distance 7.6 mm). Up to six PCBs (192 electrodes; 93 cm(2)) were used simultaneously. Slow-wave activity was characterized by spatiotemporal mapping, and regional frequencies, amplitudes, and velocities were defined and compared. Slow-wave activity in the pacemaker region (mid to upper corpus, greater curvature) was of greater amplitude (mean 0.57 mV) and higher velocity (8.0 mm/s) than the corpus (0.25 mV, 3.0 mm/s) (P < 0.001) and displayed isotropic propagation. A marked transition to higher amplitude and velocity activity occurred in the antrum (0.52 mV, 5.9 mm/s) (P < 0.001). Multiple (3-4) wavefronts were found to propagate simultaneously in the organoaxial direction. Frequencies were consistent between regions (2.83 +/- 0.35 cycles per min). HR mapping has provided a more complete understanding of normal human gastric slow-wave activity. The pacemaker region is associated with high-amplitude, high-velocity activity, and multiple wavefronts propagate simultaneously. These data provide a baseline for future HR mapping studies in disease states and will inform noninvasive diagnostic strategies.

Background & Aims Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, so the diseases therefore 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, treated at the University of Mississippi Medical Center, and from 9 controls (individuals undergoing bariatric surgery but 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 cm2). Results from patients with CUNV were compared to those of controls as well as patients with gastroparesis who were previously studied by identical methods. Results Patients with CUNV had fewer ICCs than controls (mean 3.5 vs 5.6 bodies/field; P<.05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1/9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wave front 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 those with gastroparesis (mean 3.5 vs 2.3 bodies/field; 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.

High-resolution, multi-electrode mapping is providing valuable new insights into the origin, propagation, and abnormalities of gastrointestinal (GI) slow wave activity. Construction of high-resolution mapping arrays has previously been a costly and time-consuming endeavor, and existing arrays are not well suited for human research as they cannot be reliably and repeatedly sterilized. The design and fabrication of a new flexible printed circuit board (PCB) multi-electrode array that is suitable for GI mapping is presented, together with its in vivo validation in a porcine model. A modified methodology for characterizing slow waves and forming spatiotemporal activation maps showing slow waves propagation is also demonstrated. The validation study found that flexible PCB electrode arrays are able to reliably record gastric slow wave activity with signal quality near that achieved by traditional epoxy resin-embedded silver electrode arrays. Flexible PCB electrode arrays provide a clinically viable alternative to previously published devices for the high-resolution mapping of GI slow wave activity. PCBs may be mass-produced at low cost, and are easily sterilized and potentially disposable, making them ideally suited to intra-operative human use.

Background The significance of gastric dysrhythmias remains uncertain. Progress requires a better understanding of dyrshythmic behaviors, including the slow wave patterns that accompany or promote them. The aim of this study was to use high-resolution (HR) spatiotemporal mapping to characterize and quantify the initiation and conduction of porcine gastric dysrhythmias. Methods HR mapping was performed on healthy fasted weaner pigs under general anesthesia. Recordings were made from the gastric serosa using flexible arrays (160–192 electrodes; 7.6mm spacing). Dysrhythmias were observed to occur in 14 of 97 individual recordings (from 8 out of 16 pigs), and these events were characterized, quantified and classified using isochronal mapping and animation. Key Results All observed dysrhythmias originated in the corpus and fundus. The range of dysrhythmias included incomplete conduction block (n=3 pigs; 3.9±0.5 cpm; normal range: 3.2±0.2 cpm) complete conduction block (n=3; 3.7±0.4 cpm), escape rhythm (n=5; 2.0±0.3 cpm), competing ectopic pacemakers (n=5, 3.7±0.1 cpm) and functional re-entry (n=3, 4.1±0.4 cpm). Incomplete conduction block was observed to self-perpetuate due to retrograde propagation of wave fragments. Functional re-entry occurred in the corpus around a line of unidirectional block. ‘Double potentials’ were observed in electrograms at sites of re-entry and at wave collisions. Conclusions & Inferences Intraoperative multi-electrode mapping of fasted weaner healthy pigs detected dysrhythmias in 15% of recordings (from 50% of animals), including patterns not previously reported. The techniques and findings described here offer new opportunities to understand the nature of human gastric dysrhythmias.