The Gastric Conduction System in Health and Disease: A Translational Review

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.

Effectiveness of oral phloroglucinol as a premedication for unsedated esophagogastroduodenoscopy: A prospective, double-blinded, placebo-controlled, randomized trial

Background Anti-spasmodic agents are commonly injected during esophagogastroduodenoscopy (EGD) to improve visualization of the gastric mucosa by inhibiting gastrointestinal (GI) peristalsis. The availability of oral anti-spasmodic agents would increase convenience. In this study, we evaluated the effectiveness of oral phloroglucinol (Flospan®) as a premedication for unsedated EGD. Methods A prospective, double-blinded, placebo-controlled, randomized controlled trial was conducted in a tertiary hospital. Individuals scheduled to undergo unsedated EGD were randomly assigned to receive either oral phloroglucinol or matching placebo 15 min before EGD. The primary outcome was the rate of complete gastric peristalsis suppression. Outcomes were assessed by independent investigators according to the classification of gastric peristalsis and ease of intragastric observation at the beginning (Period A) and end (Period B) of EGD. Results Overall, 71 phloroglucinol-treated and 71 placebo-treated participants (n = 142 total) were included. The phloroglucinol group showed significantly higher proportions of participants with complete gastric peristalsis suppression than the placebo group (22.5% vs. 9.9%, P = 0.040). The ease of intragastric observation was significantly better in the phloroglucinol group than in the placebo group at Periods A (P < 0.001) and B (P = 0.005). Patients in both groups had comparable adverse events and showed willingness to take the premedication at their next examination. Conclusions Oral phloroglucinol significantly suppressed gastrointestinal peristalsis during unsedated EGD compared with placebo (Clinical trial registration number: NCT03342118).

PIV and CFD studies on analyzing intragastric flow phenomena induced by peristalsis using a human gastric flow simulator

The intragastric flow phenomena was analyzed using a human gastric flow simulator. The flow-field induced by gastric peristalsis was quantitatively measured in both liquid and liquid-solid gastric contents.

Prostaglandin regulation of gastric slow waves and peristalsis

Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE2 on slow waves in the murine stomach. PGE2 increased slow-wave frequency, and this effect was mimicked by EP3, but not by EP2, receptor agonists. Chronotropic effects were due to EP3 receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W V mice. Although the integrated chronotropic effects of EP3 receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP3 receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis.

Is normal gastric emptying a predictor of normal gastric function?

Summary Aim: Impaired gastric emptying is common in many disorders. Assuming that gastric disorders primarily affect gastric peristalsis, which secondarily results in impaired emptying, the aim of our study was to evaluate whether quantitative analysis of gastric peristalsis might be a more sensitive parameter than gastric emptying to demonstrate functional gastric impairment. Patients, methods: Gastric emptying was determined scintigraphically in 141 adult (age: 18–78 years) patients (long-term Type 1 diabetes mellitus, 82 cases; systemic sclerosis, 31 cases; atrophic gastritis, 28 cases) and 20 healthy age-matched controls after ingestion of a semiliquid test meal. In addition, gastric peristalsis was evaluated by Fourier analysis of condensed images. Results: Compared to the control persons emptying was delayed in 75/141 patients, regular in 63/141 patients, and accelerated in 3/141 patients. As expected, 81% of patients with delayed emptying presented with diminished gastric contraction amplitudes. However, independent of the aetiology of the underlying disorder, 40/63 patients with regular emptying also exhibited reduced peristalsis. Conclusion: Normal gastric emptying does not predict normal gastric function. This assumption is supported by the presence of reduced amplitudes in subgroups of patients with various disorders and normal emptying. Our results suggest that the amplitude of gastric contractions may represent a more sensitive parameter for the detection of gastric dysfunction than does gastric emptying.

Properties of Electrical Rhythmicity in the Stomach

Gastric peristaltic contractions are the basis for emptying of solids from the stomach. These events begin in the mid to high corpus region, develop into a ring around the stomach, and spread down the length of the stomach to the pylorus. The pressure wave resulting from gastric peristalsis pushes the contents of the stomach toward the pyloric sphincter, but a nearly simultaneous contraction of the ring of muscle in the pyloric canal and the terminal antrum ultimately forces much of the food in the retrograde direction, toward the body of the stomach. Sheer forces that develop as a result of this forceful retropulsion cause mechanical disruption of solid particles. Repetitive peristaltic contractions (e.g., in the human these events occur about 3 times per minute), over a period of time, reduces ingested foods to small particles. The action of gastric peristalsis in the distal stomach facilitates emptying and the reduced particle diameter aides in chemical digestion of foods in the small intestine. Pathophysiological conditions that disrupt or disorganize gastric peristalsis can impair or delay normal gastric emptying. Gastric peristaltic contractions result from depolarization of the plasma membranes of smooth muscle cells. For many years it has been known that gastric muscles display periodic (or rhythmic) electrical activity in which membrane potential oscillates between negative potentials and more depolarized levels. The oscillations in membrane potential are known as electrical slow waves (see Color Figs. 2.1 and 2.2 in separate color insert). Slow waves are generated within the tunica muscularis of the proximal corpus along the greater curvature of the stomach, and these events spread around the circumference and down the stomach to the pylorus. A greater velocity of propagation around the stomach than down the stomach causes development of a ring of excitation, and this is the electrical basis underlying gastric peristaltic contractions. Studies have shown that electrical slow waves are generated by specialized pacemaker cells, known as interstitial cells of Cajal (ICCs). The main pacemaker ICCs in the stomach form a dense network of electrically coupled cells between the circular and longitudinal muscle layers of the corpus and antrum.