Inter-organ Communication in the Gut: Elucidating Electromechanical Coupling across the Gastroduodenal Junction
Electromechanical coupling of the gastroduodenal junction (GDJ) has been indicated as a target for clinical management of disorders of gut-brain interaction (DGBI) and dysmotililty conditions. Rhythmic ‘slow waves’, generated by interstitial cells of Cajal (ICC), and myogenic ‘spikes’ are bioelectrical mechanisms underpinning gastrointestinal (GI) motility, though their relationship with clinical pathophysiology is still emerging. Currently, clinical management of GI disorders is limited to inconsistent tests and symptomatic profiling, neither of which reflect the underlying pathophysiology of the typically unspecific symptoms experienced by many patients. Consequently, treatments often progress along a trial-and-error pathway, whereby patients may be exposed to a multitude of pharmaceutical and surgical interventions, with many experiencing refractory symptoms. Following an evaluation of the literature, high-resolution electrode arrays and anatomically-specific electrode cradles were designed for measurement of bioelectrical and mechanical activity across the in vivo GDJ. Subsequently, simultaneous impedance planimetry (EndoFLIP) enabled visualisation of electromechanical coupling, and immunohistochemistry revealed functional anatomy. Finally, measurements were conducted to elucidate the effect of prokinetics and truncal vagotomy on electromechanical coupling. In the future, these electromechanical measurement techniques and documented physiological phenomena will be fundamental in the reclassification of healthy and dysfunctional gastroduodenal motility. Where current clinical practice must utilise symptom profiles and inconsistent tests, followed by trial and error treatment pathways, this thesis forms foundational evidence for biomarker-driven diagnoses and appropriate treatments - whereby diseases are instead characterised, diagnosed, and treated based upon their organic cause, on a patient-by-patient level. In conclusion, engineering design, medical imaging, and physiological experimentation were developed and utilised to describe electromechanical coupling at the GDJ.
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