A theoretical study of the initiation, maintenance and termination of gastric slow wave re-entry

Abstract

Gastric slow wave dysrhythmias are associated with motility disorders. Periods of tachygastria associated with slow wave re-entry were recently recognized as one important dysrhythmia mechanism, but factors promoting and sustaining gastric reentry are currently unknown. This study reports two experimental forms of gastric re-entry and presents a series of multi-scale models that define criteria for slow wave re-entry initiation, maintenance, and termination. High-resolution electrical mapping was conducted in porcine and canine models and two spatiotemporal patterns of re-entrant activities were captured: single-loop rotor and double-loop figure-of-eight. Two separate multi-scale mathematical models were developed to reproduce the velocity and entrainment frequency of these experimental recordings. A single-pulse stimulus was used to invoke a rotor re-entry in the porcine model and a figure-of-eight re-entry in the canine model. In both cases, the simulated re-entrant activities were found to be perpetuated by tachygastria that was accompanied by a reduction in the propagation velocity in the re-entrant pathways. The simulated re-entrant activities were terminated by a single-pulse stimulus targeted at the tip of re-entrant wave, after which normal antegrade propagation was restored by the underlying intrinsic frequency gradient. Main findings: (i) the stability of re-entry is regulated by stimulus timing, intrinsic frequency gradient and conductivity; (ii) tachygastria due to re-entry increases the frequency gradient while showing decreased propagation velocity; (iii) re-entry may be effectively terminated by a targeted stimulus at the core, allowing the intrinsic slow wave conduction system to re-establish itself.

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

“…As noted by Publicover et al., the gastric frequency‐velocity relationship similarly contributes to the regulation of spacing between gastric contractions, potentially aiding in the optimization of peristalsis and mixing. Our models indicate that refractory tail interactions are responsible for this phenomenon, whereby wavefront speed drops as a response to encroachment on the tail of previous events, likely based on ion channel recovery kinetics . These observations are supported by the work of Lammers et al.…”

“…confirmed and expanded these findings in vitro in isolated canine gastric tissue strips, and more recently Du et al. also predicted a theoretical reduction in velocity within re‐entrant gastric wavefronts as rotor frequencies increased …”

“…The extracellular potentials were calculated over the range of velocities observed experimentally (ie, 2 to 10 mm s −1 ) by adjusting the pacing intervals. The remaining setup and numerical procedures of both models were as previously described …”

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

“…), whereas previous studies have also identified double rotors in the stomach, which was also defined as figure‐of‐eight re‐entry (Du et al . b ). During the rotor re‐entry, the anterior serosal surface showed rapid circumferential propagation, giving rise to both anterograde and retrograde wavefronts.…”

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

“…The zero‐flux boundary conditions and Euler numerical solution procedures were employed (refer Ref. for details). The entrained frequency was 3.0 cpm over an underlying intrinsic frequency gradient of 3.0–2.4 cpm .…”