Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping.

BACKGROUND & AIMS Interstitial cells of Cajal (ICC) generate slow waves. Disrupted ICC networks and gastric dysrhythmias are each associated with gastroparesis. However, there are no data on the initiation and propagation of slow waves in gastroparesis because research tools have lacked spatial resolution. We applied high-resolution electrical mapping to quantify and classify gastroparesis slow-wave abnormalities in spatiotemporal detail. METHODS Serosal high-resolution mapping was performed using flexible arrays (256 electrodes; 36 cm(2)) at stimulator implantation in 12 patients with diabetic or idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and amplitude field mapping, and propagation animation. ICC numbers were determined from gastric biopsy specimens. RESULTS Mean ICC counts were reduced in patients with gastroparesis (2.3 vs 5.4 bodies/field; P < .001). Slow-wave abnormalities were detected by high-resolution mapping in 11 of 12 patients. Several new patterns were observed and classified as abnormal initiation (10/12; stable ectopic pacemakers or diffuse focal events; median, 3.3 cycles/min; range, 2.1-5.7 cycles/min) or abnormal conduction (7/10; reduced velocities or conduction blocks; median, 2.9 cycles/min; range, 2.1-3.6 cycles/min). Circumferential conduction emerged during aberrant initiation or incomplete block and was associated with velocity elevation (7.3 vs 2.9 mm s(-1); P = .002) and increased amplitudes beyond a low base value (415 vs 170 μV; P = .002). CONCLUSIONS High-resolution mapping revealed new categories of abnormal human slow-wave activity. Abnormalities of slow-wave initiation and conduction occur in gastroparesis, often at normal frequency, which could be missed by tests that lack spatial resolution. Irregular initiation, aberrant conduction, and low amplitude activity could contribute to the pathogenesis of gastroparesis.

[1]  Z. Lin,et al.  Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis , 2009, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[2]  A. Pullan,et al.  Origin, propagation and regional characteristics of porcine gastric slow wave activity determined by high‐resolution mapping , 2010, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[3]  M. Camilleri,et al.  Consensus Recommendations for Gastric Emptying Scintigraphy: A Joint Report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine , 2008, The American Journal of Gastroenterology.

[4]  M. Bortolotti,et al.  Gastric Myoelectric Activity in Patients with Chronic Idiopathic Gastroparesis , 1990 .

[5]  P. Nielsen,et al.  High-resolution Mapping of In Vivo Gastrointestinal Slow Wave Activity Using Flexible Printed Circuit Board Electrodes: Methodology and Validation , 2009, Annals of Biomedical Engineering.

[6]  Kalpesh Besherdas,et al.  Abnormalities of the electrogastrogram in functional gastrointestinal disorders , 1999, American Journal of Gastroenterology.

[7]  Andrew J. Pullan,et al.  Improved signal processing techniques for the analysis of high resolution serosal slow wave activity in the stomach , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[8]  P. Pasricha,et al.  Ultrastructural differences between diabetic and idiopathic gastroparesis , 2012, Journal of cellular and molecular medicine.

[9]  G. Farrugia,et al.  Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years , 2010, Gut.

[10]  T. Ordög,et al.  Interstitial cells of Cajal in diabetic gastroenteropathy , 2007, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[11]  Leo K. Cheng,et al.  High-resolution entrainment mapping of gastric pacing: a new analytical tool. , 2010, American journal of physiology. Gastrointestinal and liver physiology.

[12]  Leo K. Cheng,et al.  A novel laparoscopic device for measuring gastrointestinal slow-wave activity , 2009, Surgical Endoscopy.

[13]  G O'Grady,et al.  High‐resolution spatial analysis of slow wave initiation and conduction in porcine gastric dysrhythmia , 2011, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[14]  Andrew J. Pullan,et al.  Falling-Edge, Variable Threshold (FEVT) Method for the Automated Detection of Gastric Slow Wave Events in High-Resolution Serosal Electrode Recordings , 2010, Annals of Biomedical Engineering.

[15]  R. McCallum,et al.  Abnormal gastric myoelectrical activity and delayed gastric emptying in patients with symptoms suggestive of gastroparesis , 1996, Digestive Diseases and Sciences.

[16]  Luc Ver Donck,et al.  Origin and propagation of the slow wave in the canine stomach: the outlines of a gastric conduction system. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[17]  B. Kuo,et al.  Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule , 2010, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[18]  J. L. Grashuis,et al.  What is measured in electrogastrography? , 1980, Digestive Diseases and Sciences.

[19]  Andrew J. Pullan,et al.  Quantification of velocity anisotropy during gastric electrical arrhythmia , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[20]  P. Pasricha,et al.  Clinical‐histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium , 2012, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[21]  F. Edwards,et al.  Propagation of slow waves in the guinea‐pig gastric antrum , 2006, The Journal of physiology.

[22]  K. Sanders,et al.  Movement based artifacts may contaminate extracellular electrical recordings from GI muscles , 2011, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[23]  Leo K. Cheng,et al.  A multiscale model of the electrophysiological basis of the human electrogastrogram. , 2010, Biophysical journal.

[24]  Leo K. Cheng,et al.  Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping. , 2010, American journal of physiology. Gastrointestinal and liver physiology.

[25]  P. Pasricha,et al.  Cellular changes in diabetic and idiopathic gastroparesis. , 2011, Gastroenterology.

[26]  W. Hasler,et al.  Directed endoscopic mucosal mapping of normal and dysrhythmic gastric slow waves in healthy humans , 2004, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[27]  W. Lammers,et al.  Focal activities and re-entrant propagations as mechanisms of gastric tachyarrhythmias. , 2008, Gastroenterology.

[28]  G O'Grady,et al.  Rapid high‐amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias , 2012, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[29]  B. Bravenboer,et al.  Hyperglycemia induces abnormalities of gastric myoelectrical activity in patients with type I diabetes mellitus. , 1994, Gastroenterology.

[30]  Leo K. Cheng,et al.  The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail , 2012, BMC Gastroenterology.

[31]  P. Pasricha,et al.  Rhythmic and Spatial Abnormalities of Gastric Slow Waves in Patients With Functional Dyspepsia , 2009, Journal of clinical gastroenterology.

[32]  H. Parkman,et al.  Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force , 2003, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[33]  Andrew J. Pullan,et al.  An Improved Method for the Estimation and Visualization of Velocity Fields from Gastric High-Resolution Electrical Mapping , 2012, IEEE Transactions on Biomedical Engineering.

[34]  G. Farrugia Interstitial cells of Cajal in health and disease , 2008, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[35]  J. Jalife,et al.  Cardiac Electrophysiology: From Cell to Bedside , 1990 .

[36]  Leo K. Cheng,et al.  Tissue-specific mathematical models of slow wave entrainment in wild-type and 5-HT(2B) knockout mice with altered interstitial cells of Cajal networks. , 2010, Biophysical journal.

[37]  Andrew J. Pullan,et al.  Automated Gastric Slow Wave Cycle Partitioning and Visualization for High-resolution Activation Time Maps , 2010, Annals of Biomedical Engineering.

[38]  K. Koch The electrifying stomach , 2011, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[39]  R A Ross,et al.  Gastric pacing improves emptying and symptoms in patients with gastroparesis. , 1998, Gastroenterology.

[40]  W. Hasler,et al.  Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside. VI. Pathogenesis and therapeutic approaches to human gastric dysrhythmias. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[41]  G. O’Grady Gastrointestinal extracellular electrical recordings: fact or artifact? , 2012, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.