Rapid high‐amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias

Abstract

Background Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that: i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; iii) the driving network conductance might switch between ICC-MP and circular ICC-IM during circumferential propagation; iv) extracellular amplitudes and velocities are correlated. Methods An experimental-theoretical study was performed. HR gastric mapping was performed in pigs during normal activation, pacing and dysrhythmia. Activation profiles, velocities and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modelled as a function of membrane potentials. Key Results High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments, was faster than longitudinal propagation (8.9 vs 6.9 mm/s; p=0.004), and of higher amplitude (739 vs 528 μV; p=0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (p<0.001). Conclusions & Inferences The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks.

Experimental evidence and mathematical modeling of thermal effects on human colonic smooth muscle contractility

“…Particularly, external electrical stimulations could also be studied, as stretch-induced contractions, blocking the neural activity to better identify the role of ICCs in modulating the contractile response to cooling. Moreover, in vitro tissue studies have demonstrated that some inflammatory mediators, especially prostaglandins, can modulate the frequency of contractions in the stomach (50,73); for this reason, use of selective inhibitors would help to better explore the mechanism responsible for the cooling contractile response of smooth muscle tissue. An extended data set for a wider range of thermal conditions would also help to unveil the contractile response of longitudinal-and circular-oriented human colonic strips.…”

Numerical metrics for automated quantification of interstitial cell of Cajal network structural properties

“…metric potential physiological relevance density measures the ICC network volume, reflecting the amount of bioelectrical current generated thickness measures the width of cellular structures within the ICC network, which may impact electrical activity propagation through the network hole size reflects the distribution of ICC throughout the tissue (i.e. the 'tightness' of the network), and may relate to the uniformity of SMC activation contact ratio indicates the availability of conduction pathways from ICC to non-ICC regions within the MP, which may (through field coupling conduction mechanism [32]) relate to the efficiency of pacemaker activity conduction into SMC connectivity reflects the structural integrity of the ICC network, indicating the cohesion of entrainment pathways [33] anisotropy indicates the degree of preferential alignment of ICC structures, and may reflect the dominant slow wave propagation direction, potentially affecting predilection and resilience to dysrhythmia [34] rsif.royalsocietypublishing.org J R Soc Interface 10: 20130421…”

Gastric Arrhythmias in Gastroparesis

“…10 Wavefronts spread out rapidly and circumferentially from the pacemaker, however, by the mid-corpus, complete rings of activation have formed such that the rapid circumferential conduction ceases, and the rings thereafter move slowly and longitudinally down the stomach (Figure 1B). 11,13 Importantly, during gastric arrhythmias, rapid circumferential propagation re-emerges to become a major determinant of conduction patterns, as a consequence of either ectopic pacemaking or disruption to the normal ring wavefronts by conduction blocks (Figure 2). 10,13 …”

“…11,13 Importantly, during gastric arrhythmias, rapid circumferential propagation re-emerges to become a major determinant of conduction patterns, as a consequence of either ectopic pacemaking or disruption to the normal ring wavefronts by conduction blocks (Figure 2). 10,13 …”