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.