This article reviews and places into context the development of lower oesophageal sphincter (LOS) manometry, the key technique for researching the mechanics of this region. The first of two major challenges, being able to record sphincter pressure accurately with generally available equipment, was solved by the advent of perfused manometry in the 1960s. The other main challenge was to achieve reliable, continuous recording of LOS pressure, despite the constant movements of the LOS relative to the manometric catheter. Though well documented, this challenge is still poorly understood and prioritised, as many clinical/diagnostic and research manometric studies use methods for LOS manometry that are invalidated by LOS movement. There are two techniques that can record continuously from the LOS, despite its movements: high resolution manometry (HRM), which uses multiple point pressure sensors spaced at 1 cm interval or less, and the sleeve, which is a single long sensor. HRM provides valuable additional information on the varied topography of pressure patterns across the gastro-oesophageal junction and how this can change in an individual, second to second. HRM especially, but also sleeve manometry continue to advance understanding of the mechanics of gastro-oesophageal reflux, to unravel the mysteries of the mechanics of hiatus hernia and the diaphragmatic hiatus, to define why antireflux surgery fails or causes dysphagia, to recognise patients with dysphagia due to isolated defects of LOS relaxation and to test novel therapies for reflux disease directed at LOS function. Ample evidence now exists that accurate monitoring of LOS and gastro-oesophageal junction pressures is important for the diagnostic assessment of many patients and for advancing research into several aspects of the mechanical function of the LOS and its surrounding structures. This evidence now needs to be better reflected in the methods used for routine clinical practice and research.
To elucidate the mechanisms involved in the relaxing effect of 2-amino-4, 4α-dihydro-4α-7-dimethyl-3H-phenoxazine-3-one (Phx-1) on smooth muscle, we investigated its effects on the contraction of both intact and skinned (cell membrane permeabilized) preparations from the guinea pig taenia cecum. In intact preparations, Phx-1 concentration-dependently suppressed the contraction induced by either acetylcholine (ACh) or high-K+ with an IC50 value estimated at around 100 μM. Similar inhibitory actions of Phx-1 on force were observed in intracellular Ca store depleted preparations. In cell membrane depolarized preparations in the absence of extracellular Ca, however, Phx-1 had little effect on either caffeine- or ACh-induced contractions. In skinned preparations, Phx-1 suppressed Ca2+-induced contractions at concentrations higher than 100 μM. These results suggest that inhibition of smooth muscle contraction by Phx-1 is due mainly to inhibition of Ca2+-influx, although Phx-1 also seems to have direct inhibitory effects on the activities of the contractile apparatus.
Recent investigations in humans point out to a disturbing effect of auditory stimuli on the functional integrity of the brain-gut axis. The study was devoted to a systematic comparative evaluation of the effect of noises of different frequency spectra on the postprandial electrical and transport functions of the digestive tract in humans. Twenty six healthy subjects attended a cross-over study, which aimed at comparison of the effect of pink contrasted to blue noise within a given category (band or tonal) and a meal stimulus type (semi-liquid or solid test meal). A panel of noninvasive measurement methods was applied: heart rate variability (HRV) analysis, surface electrogastrography, 13CO2 breath tests for gastric emptying (GE), lactulose hydrogen breath test for orocecal transit time (OCTT). The blue tonal noise was rated the most annoying one, whereas solely the pink noises exerted discernible cardiovascular effects. No one of the four noises was capable of overriding the meal-induced preponderance of the sympathetic tone. The postprandial gastric myoelectrical activity and the GE of either the semiliquid or the solid test meal appeared to be `resistant' to the noise exposure, irrespective of the noise type. Similar was the finding in the case of the OCTT, with the exception of a statistically significant retardation of the OCTT with the blue band noise. Ingestion of mixed caloric meals seems to elicit a protective influence against noise-elicited derangements of the functional integrity of the digestive tract proven formerly to occur during the fasting period.