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 Until recently, investigations of the normal patterns of motility of the healthy human colon have been limited by the resolution of in vivo recording techniques. Methods We have used a new, high-resolution fiber-optic manometry system (72 sensors at 1-cm intervals) to record motor activity from colon in 10 healthy human subjects. Key Results In the fasted colon, on the basis of rate and extent of propagation, four types of propagating motor pattern could be identified: (i) cyclic motor patterns (at 2–6/min); (ii) short single motor patterns; (iii) long single motor patterns; and (iv) occasional retrograde, slow motor patterns. For the most part, the cyclic and short single motor patterns propagated in a retrograde direction. Following a 700 kCal meal, a fifth motor pattern appeared; high-amplitude propagating sequences (HAPS) and there was large increase in retrograde cyclic motor patterns (5.6±5.4/2 h vs 34.7±19.8/2 h; p < 0.001). The duration and amplitude of individual pressure events were significantly correlated. Discriminant and multivariate analysis of duration, gradient, and amplitude of the pressure events that made up propagating motor patterns distinguished clearly two types of pressure events: those belonging to HAPS and those belonging to all other propagating motor patterns. Conclusions & Inferences This work provides the first comprehensive description of colonic motor patterns recorded by high-resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin.
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.
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.
Background The pig is a popular model for gastric electrophysiology studies. However, its normal baseline gastric activity has not been well characterized. High-resolution (HR) mapping has recently enabled an accurate description of human and canine gastric slow wave activity, and was employed here to define porcine gastric slow wave activity. Methods Fasted pigs underwent HR mapping following anesthesia and laparotomy. Flexible printed-circuit-board arrays were used (160–192 electrodes; spacing 7.62 mm). Anterior and posterior surfaces were mapped simultaneously. Activation times, velocities, amplitudes and frequencies were calculated, and regional differences evaluated. Key Results Mean slow wave frequency was 3.22 ± 0.23 cpm. Slow waves propagated isotropically from the pacemaker site (greater curvature, mid-fundus). Pacemaker activity was of higher velocity (13.3 ± 1.0 mm s−1) and greater amplitude (1.3 ± 0.2 mV) than distal fundal activity (9.0 ± 0.6 mm s−1, 0.9 ± 0.1 mV; P < 0.05). Velocities and amplitudes were similar in the distal fundus, proximal corpus (8.4 ± 0.8 mm s−1, 1.0 ± 0.1 mV), distal corpus (8.3 ± 0.8 mm s−1, 0.9 ± 0.2 mV) and antrum (6.8 ± 0.6 mm s−1, 1.1 ± 0.2 mV). Activity was continuous across the anterior and posterior gastric surfaces. Conclusions & Inferences This study has quantified normal porcine gastric slow wave activity at HR during anesthesia and laparotomy. The pacemaker region was associated with high-amplitude, high-velocity slow wave activity compared to the activity in the rest of the stomach. The increase in distal antral slow wave velocity and amplitude previously described in canines and humans is not observed in the pig. Investigators should be aware of these inter-species differences.
LARS is common, but there is substantial variation in the reporting of functional outcomes after low anterior resection. Most studies have focused on incontinence, omitting other symptoms that correlate with patients' quality of life. To improve and standardize research into LARS, a consensus definition should be developed, and these findings should inform this goal.
High resolution (HR) multi-electrode mapping is increasingly being used to evaluate gastrointestinal slow wave behaviors. To create the HR-activation maps from gastric serosal electrode recordings that quantify slow wave propagation, it is first necessary to identify the activation time (AT) of each individual slow wave event. Identifying these ATs has been a time consuming task, because there has previously been no reliable automated detection method. We have developed an automated AT detection method termed falling-edge, variable threshold (FEVT) detection. It computes a detection signal transform to accentuate the high 'energy' content of the falling edges in the serosal recording, and uses a running median estimator of the noise to set the time-varying detection threshold. The FEVT method was optimized, validated, and compared to other potential algorithms using in-vivo HR recordings from a porcine model. FEVT properly detects ATs in a wide range of waveforms, making its performance substantially superior to the other methods, especially for low signal-to-noise ratio (SNR) recordings. The algorithm offered a substantial time savings (>100 times) over manual-marking whilst achieving a highly satisfactory sensitivity (0.92) and positive-prediction value (0.89).
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