Mapping the rat gastric slow-wave conduction pathway: bridging in vitro and in vivo methods, revealing a loosely coupled region in the distal stomach.

Rhythmic electrical events, termed slow waves, govern the timing and amplitude of phasic contractions of the gastric musculature. Extracellular multielectrode measurement of gastric slow waves can be a biomarker for phenotypes of motility dysfunction. However, a gastric slow-wave conduction pathway for the rat, a common animal model, is unestablished. In this study, the validity of extracellular recording was demonstrated in vitro with simultaneous intracellular and extracellular recordings and by pharmacological inhibition of slow waves. The conduction pathway was determined by in vivo extracellular recordings while considering the effect of motion. Slow-wave characteristics [means (SD)] varied regionally having higher amplitude in the antrum than the distal corpus [1.03 (0.12) mV vs. 0.75 (0.31) mV; n = 7; P = 0.025 paired t test] and faster propagation near the greater curvature than the lesser curvature [1.00 (0.14) mm·s-1 vs. 0.74 (0.14) mm·s-1; n = 9 GC, 7 LC; P = 0.003 unpaired t test]. Notably, in some subjects, separate wavefronts propagated near the lesser and greater curvatures with a loosely coupled region occurring in the area near the distal corpus midline at the interface of the two wavefronts. This region had either the greater or lesser curvature wavefront propagating through it in a time-varying manner. The conduction pattern suggests that slow waves in the rat stomach form annular wavefronts in the antrum and not the corpus. This study has implications for interpretation of the relationship between slow waves, the interstitial cells of Cajal network structure, smooth muscles, and gastric motility.NEW & NOTEWORTHY Mapping of rat gastric slow waves showed regional variations in their organization. In some subjects, separate wavefronts propagated near the lesser and greater curvatures with a loosely coupled region near the midline, between the wavefronts, having a varying slow-wave origin. Furthermore, simultaneous intracellular and extracellular recordings were concordant and independent of movement artifacts, indicating that extracellular recordings can be interpreted in terms of their intracellular counterparts when intracellular recording is not possible.

High-energy pacing inhibits slow-wave dysrhythmias in the small intestine.

The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy.

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20-30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency 'slow wave' which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

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

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.

Biomimetic Closed-Loop Control of a Novel Soft Gastric Simulator Toward Emulating Antral Contraction Waves.

Soft gastric simulators are in vitro biomimetic modules that can reproduce the antral contraction waves (ACWs). Along with providing information concerning stomach contents, stomach simulators enable experts to evaluate the digestion process of foods and drugs. Traditionally, open-loop control approaches were implemented on stomach simulators to produce ACWs. Constructing a closed-loop control system is essential to improve the simulator's ability to imitate ACWs in additional scenarios and avoid constant tuning. Closed-loop control can enhance stomach simulators in accuracy, responding to various food and drug contents, timing, and unknown disturbances. In this article, a new generation of anatomically realistic soft pneumatic gastric simulators is designed and fabricated. The presented simulator represents the antrum, the lower portion of the stomach where ACWs occur. It is equipped with a real-time feedback system to implement diverse closed-loop controllers on demand. All the details of the physical design, fabrication, and assembly process are discussed. Also, the measures taken for the mechatronics design and sensory system are highlighted in this article. Through several implementation algorithms and techniques, three closed-loop controllers, including model-based and model-free schemes are designed and successfully applied on the presented simulator to imitate ACWs. All the experimental outcomes are carefully analyzed and compared against the biological counterparts. It is demonstrated that the presented simulator can serve as a reliable tool and method to scrutinize digestion and promote novel technologies around the human stomach and the digestion process. This research methodology can also be utilized to develop other biomimetic and bioinspired applications.

A Review of In Vitro and In Silico Swallowing Simulators: Design and Applications.

Swallowing is a primary and complex behaviour that transports food and drink from the oral cavity, through the pharynx and oesophagus, into the stomach at an appropriate rate and speed. To understand this sophisticated behaviour, a tremendous amount of research has been carried out by utilising the in vivo approach, which is often challenging to perform, poses a risk to the subjects if interventions are undertaken and are seldom able to control for confounding factors. In contrast, in silico (computational) and in vitro (instrumental) methods offer an alternate insight into the process of the human swallowing system. However, the appropriateness of the design and application of these methods have not been formally evaluated. The purpose of this review is to investigate and evaluate the state of the art of in vitro and in silico swallowing simulators, focusing on the evaluation of their mechanical or computational designs in comparison to the corresponding swallowing mechanisms during various phases of swallowing (oral phase, pharyngeal phase and esophageal phase). Additionally, the potential of the simulators is also discussed in various areas of applications, including the study of swallowing impairments, swallowing medications, food process design and dysphagia management. We also address current limitations and recommendations for the future development of existing simulators.

Neural regulation of slow waves and phasic contractions in the distal stomach: a mathematical model.

Objective.Neural regulation of gastric motility occurs partly through the regulation of gastric bioelectrical slow waves (SWs) and phasic contractions. The interaction of the tissues and organs involved in this regulatory process is complex. We sought to infer the relative importance of cellular mechanisms in inhibitory neural regulation of the stomach by enteric neurons and the interaction of inhibitory and excitatory electrical field stimulation.Approach.A novel mathematical model of gastric motility regulation by enteric neurons was developed and scenarios were simulated to determine the mechanisms through which enteric neural influence is exerted. This model was coupled to revised and extended electrophysiological models of gastric SWs and smooth muscle cells (SMCs).Main results.The mathematical model predicted that regulation of contractile apparatus sensitivity to intracellular calcium in the SMC was the major inhibition mechanism of active tension development, and that the effect on SW amplitude depended on the inhibition of non-specific cation currents more than the inhibition of calcium-activated chloride current (kiNSCC= 0.77 vs kiAno1= 0.33). The model predicted that the interaction between inhibitory and excitatory neural regulation, when applied with simultaneous and equal intensity, resulted in an inhibition of contraction amplitude almost equivalent to that of inhibitory stimulation (79% vs 77% decrease), while the effect on frequency was overall excitatory, though less than excitatory stimulation alone (66% vs 47% increase).Significance.The mathematical model predicts the effects of inhibitory and excitatory enteric neural stimulation on gastric motility function, as well as the effects when inhibitory and excitatory enteric neural stimulation interact. Incorporation of the model into organ-level simulations will provide insights regarding pathological mechanisms that underpin gastric functional disorders, and allow forin silicotesting of the effects of clinical neuromodulation protocols for the treatment of these disorders.