The gastric conduction system in health and disease: a translational review

Abstract

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow wave activity in the human stomach is provided first, followed by a detailed discussion of its organisation at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a novel non-invasive gastric mapping device

“…Multiple studies have identified ICC network depletion as a pathological hallmark of both gastroparesis, and more recently CNVS, associated with a macrophage-driven immune dysregulation. 11,16–19 ICC loss leads to slow-wave irregularities and contractile dysfunction, 16,17,20 which is consistent with our data showing weak, irregular and unstable gastric myoelectrical activity and impaired meal responses. Benchmark studies have shown that ICC depletion is restricted to ∼50% of NVS patients, with the remainder showing normal ICC counts, 16,19 approximating our two subgroups.…”

“…Classifications of individual subjects as normal, abnormal or indeterminate tests were therefore undertaken by the consensus panel exclusively according to spectral analyses in this study. The following 3 features were employed, according to the Gastric Alimetry labeling and existing gastric electrophysiology literature: 20,27,52,53 presence of a meal response (power ratio >1.4 compared to a baseline period) presence of a clear and consistent dominant frequency band within the spectral plot presence of a normal rhythm (stability typically within a range of 2.5 - 3.6 cpm) Isolated stable high or low frequencies were not judged abnormal in this study. 16,17,45 …”

“…These metrics encompass spatial descriptions of gastric electrophysiological activity, providing increased sensitivity by detecting abnormal gastric activation patterns. 16,17,20,22,24,45 The spatial metrics assessed in this study were devised to measure wave propagation stability, which was previously shown to be abnormal in subsets of NVS patients in serosal HR mapping studies. 16,17 These spatial metrics included the 'spatial frequency stability' (defined as the percentage of the recording during which there is a single dominant frequency across the mapped field), 'average spatial covariance' 29 (defined as the average absolute value of the covariance between pairs of electrodes computed over the course of a recording).…”

“…7,11,[16][17][18] A dominant feature has been interstitial cell of Cajal (ICC) depletion, associated with changes in proinflammatory macrophages, 11,16,17,19 which has been linked to aberrant gastric electrical patterns recorded using high-resolution (HR) electrical mapping. 16,17,20,21 Electrogastrography (EGG) has previously been the only clinical method for evaluating gastric myoelectrical function. EGG has demonstrated consistent abnormalities in NVS, 13 however multiple limitations restricted clinical adoption, including noise susceptibility, low resolution in the face of gastric anatomical variability, inability to evaluate spatial patterns, and low specificity for disease subtypes.…”

“…7,11,16–18 A dominant feature has been interstitial cell of Cajal (ICC) depletion, associated with changes in proinflammatory macrophages, 11,16,17,19 which has been linked to aberrant gastric electrical patterns recorded using high-resolution (HR) electrical mapping. 16,17,20,21…”