Intra-operative high-resolution mapping of slow wave propagation in the human jejunum: Feasibility and initial results.

BACKGROUND: Bioelectrical slow waves are a coordinating mechanism of small intestine motility, but extracellular human studies have been restricted to a limited number of sparse electrode recordings. High-resolution (HR) mapping has offered substantial insights into spatiotemporal intestinal slow wave dynamics, but has been limited to animal studies to date. This study aimed to translate intra-operative HR mapping to define pacemaking and conduction profiles in the human small intestine. METHODS: Immediately following laparotomy, flexible-printed-circuit arrays were applied around the serosa of the proximal jejunum (128-256 electrodes; 4-5.2 mm spacing; 28-59 cm2 ). Slow wave propagation patterns were mapped, and frequencies, amplitudes, downstroke widths, and velocities were calculated. Pacemaking and propagation patterns were defined. KEY RESULTS: Analysis comprised nine patients with mean recording duration of 7.6 ± 2.8 minutes. Slow waves occurred at a frequency of 9.8 ± 0.4 cpm, amplitude 0.3 ± 0.04 mV, downstroke width 0.5 ± 0.1 seconds, and with faster circumferential velocity than longitudinal (10.1 ± 0.8 vs 9.0 ± 0.7 mm/s; P = .001). Focal pacemakers were identified and mapped (n = 4; mean frequency 9.9 ± 0.2 cpm). Disordered slow wave propagation was observed, including wavefront collisions, conduction blocks, and breakout and entrainment of pacemakers. CONCLUSIONS & INFERENCES: This study introduces HR mapping of human intestinal slow waves, and provides first descriptions of intestinal pacemaker sites and velocity anisotropy. Future translation to other intestinal regions, disease states, and postsurgical dysmotility holds potential for improving the basic and clinical understanding of small intestine pathophysiology.

Relationships between gastric slow wave frequency, velocity, and extracellular amplitude studied by a joint experimental-theoretical approach.

BACKGROUND: Gastric slow wave dysrhythmias are accompanied by deviations in frequency, velocity, and extracellular amplitude, but the inherent association between these parameters in normal activity still requires clarification. This study quantified these associations using a joint experimental-theoretical approach. METHODS: Gastric pacing was conducted in pigs with simultaneous high-resolution slow wave mapping (32-256 electrodes; 4-7.6 mm spacing). Relationships between period, velocity, and amplitude were quantified and correlated for each wavefront. Human data from two existing mapping control cohorts were analyzed to extract and correlate these same parameters. A validated biophysically based ICC model was also applied in silico to quantify velocity-period relationships during entrainment simulations and velocity-amplitude relationships from membrane potential equations. KEY RESULTS: Porcine pacing studies identified positive correlations for velocity-period (0.13 mm s-1 per 1 s, r2 =.63, P<.001) and amplitude-velocity (74 µV per 1 mm s-1 , r2 =.21, P=.002). In humans, positive correlations were also quantified for velocity-period (corpus: 0.11 mm s-1 per 1 s, r2 =.16, P<.001; antrum: 0.23 mm s-1 per 1 s, r2 =.55; P<.001), and amplitude-velocity (94 µV per 1 mm s-1 , r2 =.56; P<.001). Entrainment simulations matched the experimental velocity-period relationships and demonstrated dependence on the slow wave recovery phase. Simulated membrane potential relationships were close to these experimental results (100 µV per 1 mm s-1 ). CONCLUSIONS AND INFERENCES: These data quantify the relationships between slow wave frequency, velocity, and extracellular amplitude. The results from both human and porcine studies were in keeping with biophysical models, demonstrating concordance with ICC biophysics. These relationships are important in the regulation of gastric motility and will help to guide interpretations of dysrhythmias.

High-resolution electrical mapping of porcine gastric slow-wave propagation from the mucosal surface.

BACKGROUND: Gastric motility is coordinated by bioelectrical slow waves, and gastric dysrhythmias are reported in motility disorders. High-resolution (HR) mapping has advanced the accurate assessment of gastric dysrhythmias, offering promise as a diagnostic technique. However, HR mapping has been restricted to invasive surgical serosal access. This study investigates the feasibility of HR mapping from the gastric mucosal surface. METHODS: Experiments were conducted in vivo in 14 weaner pigs. Reference serosal recordings were performed with flexible-printed-circuit (FPC) arrays (128-192 electrodes). Mucosal recordings were performed by two methods: (i) FPC array aligned directly opposite the serosal array, and (ii) cardiac mapping catheter modified for gastric mucosal recordings. Slow-wave propagation and morphology characteristics were quantified and compared between simultaneous serosal and mucosal recordings. KEY RESULTS: Slow-wave activity was consistently recorded from the mucosal surface from both electrode arrays. Mucosally recorded slow-wave propagation was consistent with reference serosal activation pattern, frequency (P≥.3), and velocity (P≥.4). However, mucosally recorded slow-wave morphology exhibited reduced amplitude (65-72% reduced, P<.001) and wider downstroke width (18-31% wider, P≤.02), compared to serosal data. Dysrhythmias were successfully mapped and classified from the mucosal surface, accorded with serosal data, and were consistent with known dysrhythmic mechanisms in the porcine model. CONCLUSIONS & INFERENCES: High-resolution gastric electrical mapping was achieved from the mucosal surface, and demonstrated consistent propagation characteristics with serosal data. However, mucosal signal morphology was attenuated, demonstrating necessity for optimized electrode designs and analytical algorithms. This study demonstrates feasibility of endoscopic HR mapping, providing a foundation for advancement of minimally invasive spatiotemporal gastric mapping as a clinical and scientific tool.

The impact of surgical excisions on human gastric slow wave conduction, defined by high-resolution electrical mapping and in silico modeling.

BACKGROUND: Gastric contractions are coordinated by slow waves, generated by interstitial cells of Cajal (ICC). Gastric surgery affects slow wave conduction, potentially contributing to postoperative gastric dysfunction. However, the impact of gastric cuts on slow waves has not been comprehensively evaluated. This study aimed to define consequences of surgical excisions on gastric slow waves by applying high-resolution (HR) electrical mapping and in silico modeling. METHODS: Patients undergoing gastric stimulator implantation (n = 10) underwent full-thickness stapled excisions (25 × 15 mm, distal corpus) for histological evaluation, enabling HR mapping (256 electrodes; 36 cm(2) ) over and adjacent to excisions. A biophysically based in silico model of bidirectionally coupled ICC networks was developed and applied to investigate the underlying conduction mechanisms and importance of excision orientation. KEY RESULTS: Normal gastric slow waves propagated aborally (3.0 ± 0.2 cpm). Excisions induced complete conduction block and wavelets that rotated around blocks, then propagated rapidly circumferentially distal to the blocks (8.5 ± 1.2 vs normal 3.6 ± 0.4 mm/s; p < 0.01). This 'conduction anisotropy' homeostatically restored antegrade propagating gastric wavefronts distal to excisions. Excisions were associated with complex dysrhythmias in five patients: retrograde propagation (3/10), ectopics (3/10), functional blocks (2/10), and collisions (1/10). Simulations demonstrated conduction anisotropy emerged from bidirectional coupling within ICC layers and showed transverse incision length and orientation correlated with the degree of conduction distortion. CONCLUSIONS & INFERENCES: Orienting incisions in the longitudinal gastric axis causes least disruption to electrical conduction and motility. However, if transverse incisions are made, a homeostatic mechanism of gastric conduction anisotropy compensates by restoring aborally propagating wavefronts. Complex dysrhythmias accompanying excisions could modify postoperative recovery in susceptible patients.

Circumferential and functional re-entry of in vivo slow-wave activity in the porcine small intestine.

BACKGROUND: Slow-waves modulate the pattern of small intestine contractions. However, the large-scale spatial organization of intestinal slow-wave pacesetting remains uncertain because most previous studies have had limited resolution. This study applied high-resolution (HR) mapping to evaluate intestinal pacesetting mechanisms and propagation patterns in vivo. METHODS: HR serosal mapping was performed in anesthetized pigs using flexible arrays (256 electrodes; 32 × 8; 4 mm spacing), applied along the jejunum. Slow-wave propagation patterns, frequencies, and velocities were calculated. Slow-wave initiation sources were identified and analyzed by animation and isochronal activation mapping. KEY RESULTS: Analysis comprised 32 recordings from nine pigs (mean duration 5.1 ± 3.9 min). Slow-wave propagation was analyzed, and a total of 26 sources of slow-wave initiation were observed and classified as focal pacemakers (31%), sites of functional re-entry (23%) and circumferential re-entry (35%), or indeterminate sources (11%). The mean frequencies of circumferential and functional re-entry were similar (17.0 ± 0.3 vs 17.2 ± 0.4 cycle min(-1) ; P = 0.5), and greater than that of focal pacemakers (12.7 ± 0.8 cycle min(-1) ; P < 0.001). Velocity was anisotropic (12.9 ± 0.7 mm s(-1) circumferential vs 9.0 ± 0.7 mm s(-1) longitudinal; P < 0.05), contributing to the onset and maintenance of re-entry. CONCLUSIONS & INFERENCES: This study has shown multiple patterns of slow-wave initiation in the jejunum of anesthetized pigs. These results constitute the first description and analysis of circumferential re-entry in the gastrointestinal tract and functional re-entry in the in vivo small intestine. Re-entry can control the direction, pattern, and frequency of slow-wave propagation, and its occurrence and functional significance merit further investigation.

Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias.

BACKGROUND: Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC-MP) and circular interstitial cells of Cajal intramuscular (ICC-IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated. METHODS: An experimental-theoretical study was performed. High-resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials. KEY RESULTS: High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s(-1) ; P = 0.004) and of higher amplitude (739 vs 528 µV; P = 0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P < 0.001). CONCLUSIONS & INFERENCES: The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks.

A comparison of gold versus silver electrode contacts for high-resolution gastric electrical mapping using flexible printed circuit board arrays.

Stomach contractions are initiated and coordinated by electrical events termed slow waves, and slow wave abnormalities contribute to gastric motility disorders. Recently, flexible printed circuit board (PCB) multi-electrode arrays were introduced, facilitating high-resolution mapping of slow wave activity in humans. However PCBs with gold contacts have shown a moderately inferior signal quality to previous custom-built silver-wire platforms, potentially limiting analyses. This study determined if using silver instead of gold contacts improved flexible PCB performance. In a salt-bath test, modestly higher stimulus amplitudes were recorded from silver PCBs (mean 312, s.d. 89 µV) than those from gold (mean 281, s.d. 85 µV) (p < 0.001); however, the signal-to-noise ratio (SNR) was similar (p = 0.26). In eight in vivo experimental studies, involving gastric serosal recordings from five pigs, no silver versus gold differences were found in terms of slow wave amplitudes (mean 677 versus 682 µV; p = 0.91), SNR (mean 8.8 versus 8.8 dB; p = 0.94) or baseline drift (NRMS; mean 12.0 versus 12.1; p = 0.97). Under the prescribed conditions, flexible PCBs with silver or gold contacts provide comparable results in vivo, and contact material difference does not explain the performance difference between current-generation slow wave mapping platforms. Alternative explanations for this difference and the implications for electrode design are discussed.