High-resolution slow wave mapping of the in-vivo rabbit small intestine

Abstract

Gastrointestinal (GI) motility is coordinated by rhythmic underlying bioelectric events known as slow waves. The interstitial cells of cajal (ICC) are the pacemaker cells in the GI tract and they generate and mediate slow wave events. The small intestine plays a key role in digestion and enables the supply of nutrients into the bloodstream. Analysing this slow wave activity will provide us with an improved understanding of the mechanisms governing intestinal motility. Earlier studies using low-resolution techniques have observed the existence of a frequency gradient and multiple pacemakers across the intestine. However, the findings from these studies lack the spatiotemporal characteristics to define the origin and propagation of these slow waves in the intestine. The introduction of high-resolution (HR) mapping in the GI field was a major step in understanding the existence of multiple pacemaker activities and validating the spatiotemporal relationship of slow waves. However, to date it has been applied to a limited number of in-vivo animal studies. In this thesis, HR in-vivo mapping was performed on the rabbit small intestine and the sacculus rotundus located at the ileocecal junction (N = 5). The main aim of the study was to acquire slow wave signal from the rabbit small intestine. This was achieved by using flexible printed circuit board (FPCB) array contained in specialised cradles to match the circumference of the small intestine. Slow wave signals from the FPCB were digitised using a passive multi-channel electrophysiological system. To analyse the obtained the slow wave data, a signal smoothing technique with validated ventilation removal method was used to filter the slow waves. In addition, an automated marking algorithm (Falling edge variable threshold, [FEVT]) was adapted and tuned for marking the slow wave activation times. The findings of this study showed the existence of aboral propagating slow waves from the rabbit duodenum. The aboral propagation demonstrated the ability of slow waves to move the digesta across the small intestine. In addition, a consistent oral propagation was also seen in the ileum especially in the terminal ileum indicative of retroperistalsis. The change in the propagation pattern to collision and the abolishment of colliding wavefronts was captured precisely in the present invivo mapping study. The evidence of entraining slow wave activity across the terminal ileum from the sacculus rotundus was found to be consistent with the earlier Alvarez studies using low resolution mapping. This is the first successful HR mapping across the sacculus rotundus and terminal ileum illustrating spatiotemporal propagational characteristics. Furthermore, slow wave activity from the focal pacemakers was also found to be similar with the previous studies exhibiting propagation in both oral and in aboral direction. The existence of a frequency gradient across the small intestine was found to be similar to earlier animal studies. The average frequency in the duodenum of the rabbit decreased from 20.1 ± 1.2 cycles per minute (cpm) to 10.5 ± 0.8 cpm, ( < 0.002) in the terminal ileum. The existence of such a frequency gradient demonstrated that different anatomical segments can function as a pacemaker. However, an increase in frequency was evident across the SR and terminal ileum compared to the ileum (13.0 ± 1.6 cpm versus 10.8 ± 0.7 cpm, ( < 0.001)). The increase in slow wave frequency demonstrated the ability of the SR to act as a dominant distal pacemaker in maintaining the motility across the terminal ileum and towards the ileocecal junction. A transient increase in the average velocity after a declined slow wave velocity (e.g., Rabbit 2; 14.6 ± 0.7 mm/s versus 6.0 ± 1.0 mm/s, ( < 0.001)) was evident in the present rabbit studies. One rabbit exhibited a decrease in average slow wave amplitude across the small intestine (duodenum: 0.11 ± 0.01 mV versus ileum: 0.07 ± 0.01 mV, ( < 0.001)) similar to previous mapping studies. Whereas all the other four rabbits exhibited an increase in slow wave amplitude towards ileum. In addition, SR mapping studies also showed an increase in the average velocity and amplitude across the SR and terminal ileum compared to the ileum. The work presented in this thesis has illustrated an experimental approach for HR slow wave intestinal recording in rabbits. Furthermore, the data was quantified to show the dynamic electrophysiological mechanisms in a normal rabbit model. Furthermore the initial investigation in the SR and terminal ileum provides a new insights in understanding the slow wave activity from the distal end of the small intestine.