Human gastric slow wave activity redefined through high-resolution mapping

Abstract

Gastric contractions are initiated, propagated and coordinated by underlying rhythmic bioelectrical potentials termed slow waves. Slow waves propagate through the musculature via conduction networks comprised of specialised cells, and act in combination with the enteric nervous system to regulate peristalsis. Disordered slow wave activity has been associated with the pathophysiology of several motility disorders, and occurs as a result of the abnormal function of, or disruption to these specialised cells and their distribution pathways. This thesis aimed to: i) define regional variations in slow wave characteristics in the distal stomach, identified during previous high resolution (HR) mapping research, ii) explore the consequences of disruption to the bioelectrical conduction pathways and removal of the primary gastric pacemaker, and iii) develop new laparoscopic recording arrays with a view to increasing coverage and accuracy of slow wave mapping. The investigation of slow wave characteristics in the distal stomach was performed using HR mapping techniques and flexible printed circuit (FPC) electrode arrays. The arrays were positioned on the antrum and used to detect significant increases in the velocity (3.3 ± 0.1 mm s-1 vs 7.5 ± 0.6 mm s-1; p<0.01) and amplitude (1.5 ± 0.1 vs 2.5 ± 0.1 mV; p<0.01) of slow wave activity as it passes from the proximal to the prepyloric antrum. The zones of high velocity and amplitude were defined using the pyloric sphincter and the angularis incisura for reference. The region of high velocity commenced approximately 28 mm proximal to the pyloric ring, continued for 22 mm and terminated approximately 6 mm proximal to the pyloric ring. The high amplitude region commenced approximately 36 mm proximal to the pyloric ring, continued for 22 mm, and terminated approximately 14 mm orad. These results were applied to parameterise a three-dimensional geometric model of the stomach, and demonstrated the importance of the terminal antral contraction in enhancing mixing efficiency. Exploring the effects of primary pacemaker removal and disruption to slow wave conduction networks was achieved using HR mapping techniques in bariatric patients undergoing laparoscopic sleeve gastrectomy (LSG). Sterilisable FPC electrode arrays were applied to the serosal surface of the stomach in vivo, prior-to and following LSG. Patients exhibiting normal activity before LSG commonly developed a persistent antral ectopic pacemaker postoperatively, and retrograde propagation of slow waves from this region. The frequency (2.7 ± 0.3 vs 2.8 ± 0.3 cpm; p>0.05) and amplitude (1.7 ± 0.2 vs 1.6 ± 0.6 mV; p>=0.05) of slow wave cycles was unaffected, however velocity increased significantly (3.8 ± 0.8 vs 12.5 ± 0.8 mm s-1; p=0.01) following surgery. These data show that primary pacemaker removal and disruption of slow wave conduction networks causes dysrhythmic activation and propagation patterns. These may resolve naturally or potentially lead to the development of gastric motility disorders. HR mapping of a previous LSG patient reporting ongoing pain, acid reflux and food intolerance 15-months postoperatively revealed a persistent ectopic pacemaker in the antral region of the sleeve. Slow waves were found to consistently propagate around an area conduction block, and were of a higher velocity (12.6 ± 4.8 mm s-1) than anticipated. However, frequency (2.2 ± 0.01 cpm) and amplitude (2.3 ± 1.9 mV) were within normal ranges. The results suggest that pain, reflux and food intolerance following LSG may be associated with a deviation from normal bioelectrical activity patterns occurring following removal of the gastric pacemaker. The increasing adoption of minimally invasive procedures for the treatment of gastrointestinal (GI) diseases prompted the development of a laparoscopic device capable of recording slow wave activity directly from the serosal surface of the target organ. This device improved on previous designs with a larger coverage area and a greater number of electrodes; a larger field of electrodes is particularly relevant when attempting to characterise dysrhythmias, and reduce error when calculating the direction and velocity of slow waves. Simultaneous recordings from the improved design and a FPC array in pigs were identical in frequency (2.6 cpm; p>0.05). Activation patterns and velocities were also consistent (8.9 ± 0.2 vs 8.7 ± 0.1 mm s-1; p>0.05). Device and reference amplitudes were comparable (1.3 ± 0.1 vs 1.4 ± 0.1 mV; p>0.05), although the device signal to noise ratio (SNR) was higher (17.5 ± 0.6 vs 12.8 ± 0.6 dB; p<0.01). Slow wave activity was also recorded and mapped from the corpus of a human patient and was within the known physiological range for human gastric slow waves (frequency 2.7 ± 0.03 cpm), amplitude 0.8 ± 0.4 mV, velocity 2.3 ± 0.9 mm s-1). The laparoscopic device achieved high-quality gastric serosal slow wave recordings and demonstrated its potential for documenting slow wave characteristics in patients with gastric dysmotility disorders. The work within this thesis presents a series of advances that enhance our investigation and understanding of gastric slow waves. It is anticipated that these novel mapping tools, combined with improved knowledge of both normal and dysrhythmic activity will progress clinical diagnoses and patient treatment options.