High-resolution mapping of gastric slow wave uncoupling induced by glucagon

Gastrointestinal (GI) motility is in part governed by the rhythmic myoelectrical waves of the GI tract, also known as slow waves. Disordered slow wave rhythms and patterns are associated with functional motility disorders. Various drugs have been used to simulate disease states to develop and investigate the efficacy of novel therapies for treating GI disorders. Slow wave dysrhythmias associated with GI conditions are commonly characterized based on their frequency, but this metric has also been shown to be unreliable. This study induced slow wave dysrhythmias in the stomach and quantified the slow wave spatial response using high resolution mapping techniques (128 electrodes at 5 mm inter-electrode spacing). Glucagon (0.0125 mg/kg) was infused to induce hyperglycemia in pigs (n=6, 42.8 ± 8.1 kg). The resultant slow wave dysrhythmias were mapped and quantified by determining the frequency of slow wave activity and the prevalence of regions of uncoupled activity compared to the baseline recordings. At baseline, slow waves were fully entrained and propagated at a regular frequency of 3.4 ± 1.0 cycles per minute (cpm) with no presence of disordered activity. However, after the infusion of glucagon, slow wave activity was uncoupled in 3.2 - 10.9 % of the mapped region, with slow waves occurring during every alternate slow wave cycle compared to other regions. Therefore, slow wave activity in regular and uncoupled regions occurred in a 2:1 frequency ratio in the ranges between 2.1 - 3.1 cpm and 1.0 - 1.6 cpm. The findings highlighted the importance of high-resolution mapping techniques to define electrical dysrhythmias of the stomach which otherwise would have been undetected with a few sparse electrodes due to spatial aliasing. This study defined the response of gastric slow wave activity resulting from glucagon-induced hyperglycemia for the first time in pigs. In the future, the developed framework can be used to simulate disease states and assess the effectiveness of novel therapies such as pacing in treating GI disorders.