An Improved Foundation for the Investigation and Treatment of Gastric Dysrhythmia

Abstract

Gastric motility disorders remain a complex clinical challenge, and inflict a substantial burden of cost and suffering on society. Gastric contractions are coordinated by an underlying electrical activity, and gastric dysrhythmias are implicated in the pathophysiology of several motility disorders. However, the significance of dysrhythmias remains uncertain, and there are few elective therapies, because current tools to investigate dysrhythmias have low reliability owing to their lack of spatial resolution. This thesis aimed to develop an improved foundation for the investigation and management of gastric dysrhythmia, by advancing and translating high-resolution (HR; multi-electrode) spatiotemporal mapping. The research is a cross-disciplinary program of bioengineering, and basic and clinical electrophysiology. A range of HR mapping devices are first developed and validated for intra-operative gastric mapping, including at open and laparoscopic surgery. Automated signal processing tools are next validated for the efficient, reliable marking, grouping, and mapping of slow wave events, and these tools are integrated into an intuitive software platform. These methodological advances are then applied in a series of experimental studies. The origin and propagation of porcine gastric slow wave activity is defined, followed by clinical translation with the first spatiotemporal analysis of normal human gastric slow wave propagation. The methods are then applied to define new patterns and mechanisms of gastric dysrhythmia, initially in a porcine model, including the first demonstration of how rapid, high-amplitude circumferential propagation emerges during dysrhythmias. The first clinical study applying HR electrical mapping is then presented, performed on a cohort of patients with diabetic and idiopathic gastroparesis, revealing new patterns of human dysrhythmia. A new classification scheme for abnormalities of human gastric slow wave initiation and conduction is proposed. Finally, the evidence for high-frequency gastric electrical stimulation is reviewed, prior to the presentation of a new 'entrainment mapping' method for better assessing gastric pacing protocols. In total, this work constitutes a coordinated series of advances that offer a strengthened foundation for investigating and managing gastric electrical abnormalities. It is hoped that these new methods and findings will translate into future clinical advances, to improve the diagnosis and treatment of these complex patient populations.