A Tissue Framework for Simulating the Effects of Gastric Electrical Stimulation andIn VivoValidation

Abstract

Gastric pacing is used to modulate normal or abnormal gastric slow-wave activity for therapeutic purposes. New protocols are required that are optimized for motility outcomes and energy efficiency. A computational tissue model was developed, incorporating smooth muscle and interstitial cell of Cajal layers, to enable predictive simulations of slow-wave entrainment efficacy under different pacing frequencies. Concurrent experimental validation was performed via high-resolution entrainment mapping in a porcine model (bipolar pacing protocol: 2 mA amplitude; 400 ms pulse-width; 17-s period; midcorpus). Entrained gastric slow-wave activity was found to be anisotropic (circular direction: 8.51 mm s−1; longitudinal: 4.58 mm s−1), and the simulation velocities were specified accordingly. Simulated and experimental slow-wave activities demonstrated satisfactory agreement, showing similar propagation patterns and frequencies (3.5–3.6 cycles per minute), and comparable zones of entrainment (ZOEs; 64 cm2). The area of ZOE achieved was found to depend on the phase interactions between the native and entrained activities. This model allows the predictions of phase interactions between native and entrained activities, and will be useful for determining optimal frequencies for gastric pacing, including multichannel pacing studies. The model provides a framework for the development of more sophisticated predictive gastric pacing simulations in future.

Cellular automaton model for simulating tissue-specific intestinal electrophysiological activity

“…This model differs from previous slow wave propagation cellular automaton models [14, 15] in that both ICC and non-ICC node types were explicitly represented, and appropriate cellular automaton rules were applied accordingly. This facilitates investigations of structure on function at much higher spatial resolutions, which is necessary to capture the ICC network structure.…”

“…However, this methodology is computationally expensive [13], mainly due to the large number of equations and parameters present in the cell model, and hence difficulties exist in up-scaling these simulations to larger multiscale simulation studies. An alternative strategy of implementing cellular automaton models to simulate slow wave propagation has also been previously conducted [14, 15], but these previous studies focused on a larger spatial scale and did not incorporate structural detail from real ICC networks.…”

Gastrointestinal system

“…These models have been integrated with tissue and cell-level models, and are beginning to demonstrate predictive capability with application to the diagnosis and treatment of gastric diseases 58. A gradient of intrinsic pacemaker potential frequency is assigned to the ICC layer of these mathematical models, to reproduce the propagation of entrained slow waves in the smooth muscle layer.…”

“…Du et al 58. have recently performed simulations of GEA across a virtual section of stomach musculature using a biophysically based computation model.…”

“…To date, GES research has proved a technically tedious exercise, requiring laborious trial and error experiments on animal models 110. More recently, biophysically based computational models of GIEA, such as those of Du et al .,58 have shown potential to act as hypothesis-testing tools for use in defining effective protocols for improved GI stimulation. This strategy may result in increased research efficiency, by transfer of developmental work to a computational rather than animal models.…”