Optimization of pacing parameters to entrain slow wave activity in the pig jejunum

Abstract Pacing has been proposed as a therapy to restore function in motility disorders associated with electrical dysrhythmias. The spatial response of bioelectrical activity in the small intestine to pacing is poorly understood due to a lack of high-resolution investigations. This study systematically varied pacing parameters to determine the optimal settings for the spatial entrainment of slow wave activity in the jejunum. An electrode array was developed to allow simultaneous pacing and high-resolution mapping of the small intestine. Pacing parameters including pulse-width (50, 100 ms), pulse-amplitude (2, 4, 8 mA) and pacing electrode orientation (antegrade, retrograde, circumferential) were systematically varied and applied to the jejunum (n = 15 pigs). Pulse-amplitudes of 4 mA (p = 0.012) and 8 mA (p = 0.002) were more effective than 2 mA in achieving spatial entrainment while pulse-widths of 50 ms and 100 ms had comparable effects (p = 0.125). A pulse-width of 100 ms and a pulse-amplitude of 4 mA were determined to be most effective for slow wave entrainment when paced in the antegrade or circumferential direction with a success rate of greater than 75%. These settings can be applied in chronic studies to evaluate the long-term efficacy of pacing, a critical aspect in determining its therapeutic potential

Continuum Based Bioelectrical Simulations using Structurally Realistic Gastrointestinal Pacemaker Cell Networks

Cellular and tissue level bioelectrical activity was simulated over structurally realistic 3D interstitial cell of Cajal (ICC) networks reconstructed from confocal images of a wild type (WT) mouse model with a normal ICC distribution and a Spry4 knockout (KO) mouse model with a mild ICC hyperplasia. First, the ICC pixels within the confocal images were segmented. Then, the segmented images were visually inspected and the 3D surface mesh of the ICC tissue network was created from the 90 slices spanning the myenteric plexus ICC network. After two additional concentric meshes (representing the non-ICC and tissue bath regions) surrounding the ICC region were added, a 3D tetrahedral volume mesh containing the three regions was reconstructed. The electrical propagation through the tissue network was simulated using the bidomain continuum model. The results showed that the ICC network of the WT mouse had a smaller volume than the KO mouse (0.008 vs 0.012 mm3). The simulated bioelectrical activity for both mice showed an isotropic propagation from the initial activation region. Mean velocities of 4.2±1.5 and 4.1±1.3 mm/s were reported for the WT and KO mice, respectively. The velocity in the x-direction was higher than the y-direction for the WT mouse with a percent difference of 14.8%. On the other hand, the velocity in the y-direction was higher for the KO mouse with a percent difference of 9.5%. For both cases, there was no propagation in the z-direction as all the solution points along the same z-depth were simultaneously activated.SCOPUS: cp.pinfo:eu-repo/semantics/publishe