Journal
MATHEMATICAL MEDICINE AND BIOLOGY-A JOURNAL OF THE IMA
Volume 32, Issue 4, Pages 405-423Publisher
OXFORD UNIV PRESS
DOI: 10.1093/imammb/dqu023
Keywords
gastric dysrhythmia; multi-scale; slow wave; high-resolution mapping
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Funding
- National Institute of Health [R01 DK64775]
- New Zealand Health Research Council
- Riddet Institute
- Rutherford Foundation Trust
- Marsden Fast-Start Grant from Royal Society of New Zealand
- Fraunhofer-Bessel Research Award from Alexander von Humboldt Foundation
- Fraunhofer-Gesellschaft
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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 re-entry 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.
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