Abstract
Gastrointestinal motility is coordinated by slow waves (SWs) generated by the interstitial cells of Cajal (ICC). Experimental studies have shown that SWs spontaneously activate at different intrinsic frequencies in isolated tissue, whereas in intact tissues they are entrained to a single frequency. Gastric pacing has been used in an attempt to improve motility in disorders such as gastroparesis by modulating entrainment, but the optimal methods of pacing are currently unknown. Computational models can aid in the interpretation of complex in vivo recordings and help to determine optimal pacing strategies. However, previous computational models of SW entrainment are limited to the intrinsic pacing frequency as the primary determinant of the conduction velocity, and are not able to accurately represent the effects of external stimuli and electrical anisotropies. In this paper, we present a novel computationally efficient method for modeling SW propagation through the ICC network while accounting for conductivity parameters and fiber orientations. The method successfully reproduced experimental recordings of entrainment following gastric transection and the effects of gastric pacing on SW activity. It provides a reliable new tool for investigating gastric electrophysiology in normal and diseased states, and to guide and focus future experimental studies.
Similar content being viewed by others
References
Beyder, A., J. L. Rae, C. Bernard, P. R. Strege, F. Sachs, and G. Farrugia. Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel. J. Physiol. 588:4969–4985, 2010.
Buist, M. L., A. Corrias, and Y. C. Poh. A model of slow wave propagation and entrainment along the stomach. Ann. Biomed. Eng. 38:3022–3030, 2010.
Buist, M. L., and Y. C. Poh. An extended bidomain framework incorporating multiple cell types. Biophys. J. 99:13–18, 2010.
Cheng, L. K., G. O’Grady, P. Du, J. U. Egbuji, J. A. Windsor, and A. J. Pullan. Gastrointestinal system. Wiley Interdiscip. Rev. Syst. Biol. Med. 2:65–79, 2010.
Corrias, A., and M. L. Buist. A quantitative model of gastric smooth muscle cellular activation. Ann. Biomed. Eng. 35:1595–1607, 2007.
Corrias, A., and M. L. Buist. Quantitative cellular description of gastric slow wave activity. Am. J. Physiol. Gastrointest. Liver Physiol. 294:G989–G995, 2008.
Cousins, H. M., F. R. Edwards, H. Hickey, C. E. Hill, and G. D. S. Hirst. Electrical coupling between the myenteric interstitial cells of Cajal and adjacent muscle layers in the guinea-pig gastric antrum. J. Physiol. 550:829–844, 2003.
Dickens, E. J., G. D. Hirst, and T. Tomita. Identification of rhythmically active cells in guinea-pig stomach. J. Physiol. 514(Pt 2):515–531, 1999.
Du, P., G. O’Grady, J. U. Egbuji, W. J. Lammers, D. Budgett, P. Nielsen, J. A. Windsor, A. J. Pullan, and L. K. Cheng. High-resolution mapping of in vivo gastrointestinal slow wave activity using flexible printed circuit board electrodes: methodology and validation. Ann. Biomed. Eng. 37:839–846, 2009.
Du, P., G. O’Grady, S. J. Gibbons, R. Yassi, R. Lees-Green, G. Farrugia, L. K. Cheng, and A. J. Pullan. Tissue-specific mathematical models of slow wave entrainment in wild-type and 5-HT(2B) knockout mice with altered interstitial cells of Cajal networks. Biophys. J. 98:1772–1781, 2010.
Du, P., G. O’Grady, J. A. Windsor, L. K. Cheng, and A. J. Pullan. A tissue framework for simulating the effects of gastric electrical stimulation and in vivo validation. IEEE Trans. Biomed. Eng. 56:2755–2761, 2009.
El-Sharkawy, T. Y., K. G. Morgan, and J. H. Szurszewski. Intracellular electrical activity of canine and human gastric smooth muscle. J. Physiol. 279:291–307, 1978.
Farrugia, G. Interstitial cells of Cajal in health and disease. Neurogastroenterol. Motil. 20(Suppl 1):54–63, 2008.
Hinder, R. A., and K. A. Kelly. Human gastric pacesetter potential. Am. J. Surg. 133:29–33, 1977.
Hirst, G. D., and F. R. Edwards. Generation of slow waves in the antral region of guinea-pig stomach—a stochastic process. J. Physiol. 535:165–180, 2001.
Imtiaz, M. S., D. W. Smith, and D. F. van Helden. A theoretical model of slow wave regulation using voltage-dependent synthesis of inositol 1,4,5-trisphosphate. Biophys. J. 83:1877–1890, 2002.
Kim, T. W., S. D. Koh, T. Ordog, S. M. Ward, and K. M. Sanders. Muscarinic regulation of pacemaker frequency in murine gastric interstitial cells of Cajal. J. Physiol. 546:415–425, 2003.
Lees-Green, R., P. Du, G. O’Grady, A. Beyder, G. Farrugia, and A. J. Pullan. Biophysically based modeling of the interstitial cells of Cajal: current status and future perspectives. Front. Physiol. 2:29, 2011.
Lin, Z. Y., R. W. McCallum, B. D. Schirmer, and J. D. Z. Chen. Effects of pacing parameters on entrainment of gastric slow waves in patients with gastroparesis. Am. J. Physiol. Gastrointest. Liver Physiol. 274:G186–G191, 1998.
McCallum, R. W., J. D. Chen, Z. Lin, B. D. Schirmer, and R. D. Williams. Gastric pacing improves emptying and symptoms in patients with gastroparesis. Gastroenterology 114:456–461, 1998.
Mirams, G. R., C. J. Arthurs, M. O. Bernabeu, R. Bordas, J. Cooper, A. Corrias, Y. Davit, S.-J. Dunn, A. G. Fletcher, D. G. Harvey, M. E. Marsh, J. M. Osborne, P. Pathmanathan, J. Pitt-Francis, J. Southern, N. Zemzemi, and D. J. Gavaghan. Chaste: an open source C++ library for computational physiology and biology. PLoS Comput. Biol. 9:e1002970, 2013.
O’Grady, G., T. R. Angeli, P. Du, C. Lahr, W. J. E. P. Lammers, J. A. Windsor, T. L. Abell, G. Farrugia, A. J. Pullan, and L. K. Cheng. Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping. Gastroenterology 143(589–98):e1–e3, 2012.
O’Grady, G., P. Du, W. J. E. P. Lammers, J. U. Egbuji, P. Mithraratne, J. D. Z. Chen, L. K. Cheng, J. A. Windsor, and A. J. Pullan. High-resolution entrainment mapping of gastric pacing: a new analytical tool. Am. J. Physiol. Gastrointest. Liver Physiol. 298:G314–G321, 2010.
O’Grady, G., P. Du, N. Paskaranandavadivel, T. R. Angeli, W. J. E. P. Lammers, S. J. Asirvatham, I. A. Windor, G. Farrugia, A. J. Pullan, and L. K. Cheng. Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias. Neurogastroenterol. Motil. 24(7):e299–e312, 2012. doi:10.1111/j.1365-2982.2012.01932.x.
Pathmanathan, P., M. O. Bernabeu, R. Bordas, J. Cooper, A. Garny, J. M. Pitt-Francis, J. P. Whiteley, and D. J. Gavaghan. A numerical guide to the solution of the bi-domain equations of cardiac electrophysiology. Prog. Biophys. Mol. Biol. 102:136–155, 2010.
Poh, Y. C., A. Beyder, P. R. Strege, G. Farrugia, and M. L. Buist. Quantification of gastrointestinal sodium channelopathy. J. Theor. Biol. 293:41–48, 2012.
Sanders, K. M., S. D. Koh, and S. M. Ward. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu. Rev. Physiol. 68:307–343, 2006.
Ward, S. M., R. E. Dixon, A. de Faoite, and K. M. Sanders. Voltage-dependent calcium entry underlies propagation of slow waves in canine gastric antrum. J. Physiol. 561:793–810, 2004.
Yin, J., and J. D. Z. Chen. Implantable gastric electrical stimulation: ready for prime time? Gastroenterology 134:665–667, 2008.
Yoneda, S., H. Takano, M. Takaki, H. Suzuki, S. M. Ward, T. Ordög, J. R. Bayguinov, B. Horowitz, A. Epperson, L. Shen, H. Westphal, K. M. Sanders, and G. D. S. Hirst. Regenerative potentials evoked in circular smooth muscle of the antral region of guinea-pig stomach. J. Physiol. 517:563–573, 1999.
Acknowledgments
This work was supported in part by Grants from the Riddet Institute, New Zealand, Health Research Council, New Zealand and NIH (R01 DK 64775). The authors thank Mr. Niranchan Paskaranandavadivel at the Auckland Bioengineering Institute for his suggestions.
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Nathalie Virag oversaw the review of this article.
Appendices
Appendix A
Appendix B
The following plots show the comparison of different ionic channel currents describing the ICC cell behaviour for FSM-CB model and ICC-CB model.
Rights and permissions
About this article
Cite this article
Sathar, S., Trew, M.L., Du, P. et al. A Biophysically Based Finite-State Machine Model for Analyzing Gastric Experimental Entrainment and Pacing Recordings. Ann Biomed Eng 42, 858–870 (2014). https://doi.org/10.1007/s10439-013-0949-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10439-013-0949-5