Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA.

PURPOSE: There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. The rigidity of the cortical ECM limits expansion of the follicle and consequently oocyte maturation, maintaining the follicle in its quiescent state. Quiescent primordial, primary, and secondary follicles still exist in primary ovarian insufficiency (POI) patients, and techniques as in vitro activation (IVA) and drug-free IVA have recently been developed aiming to activate these follicles based on the Hippo signaling disruption that is essential in mechanotransduction. In this context, we analyze the effect of drug-free IVA in POI patients, comparing the relationship between possible resumption ovarian function and biomechanical properties of ovarian tissue. METHODS: Nineteen POI patients according to ESHRE criteria who underwent drug-free IVA by laparoscopy between January 2018 and December 2019 and were followed up for a year after the intervention. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure tissue stiffness (Young's elastic modulus, E) at the micrometer scale. Functional outcomes after drug-free were analyzed. RESULTS: Resumption of ovarian function was observed in 10 patients (52.6%) and two of them became pregnant with live births. There were no differences in clinical characteristics (age and duration of amenorrhea) and basal hormone parameters (FSH and AMH) depending on whether or not there was activation after surgery. However, ovarian cortex stiffness was significantly greater in patients with ovarian activity after drug-free IVA: median E = 5519 Pa (2260-11,296) vs 1501 (999-3474); p-value < 0.001. CONCLUSIONS: Biomechanical properties of ovarian cortex in POI patients have a great variability, and higher ovarian tissue stiffness entails a more favorable status when drug-free IVA is applied in their treatment. This status is probably related to an ovary with more residual follicles, which would explain a greater possibility of ovarian follicular reactivations after treatment.

Public health response to an outbreak of SARS-CoV2 infection in a Barcelona prison.

An outbreak of SARS-CoV2 infection in a Barcelona prison was studied. One hundred and forty-eight inmates and 36 prison staff were evaluated by rt-PCR, and 24.1% (40 prisoners, two health workers and four non-health workers) tested positive. In all, 94.8% of cases were asymptomatic. The inmates were isolated in prison module 4, which was converted into an emergency COVID unit. There were no deaths. Generalised screening and the isolation and evaluation of the people infected were key measures. Symptom-based surveillance must be supplemented by rapid contact-based monitoring in order to avoid asymptomatic spread among prisoners and the community at large.

Early effects of continuous positive airway pressure in a rodent model of allergic rhinitis.

BACKGROUND: Continuous positive airway pressure (CPAP) is the most commonly used treatment in obstructive sleep apnea. In a previous rat model study, we demonstrated that nasal CPAP induces early rhinitis expressed by nasal neutrophil extravasation. Here we hypothesized that nasal CPAP would worsen nasal inflammation on a previously inflamed mucosa. The objective of this study was to evaluate the early nasal CPAP effects of allergic rhinitis (AR) in a rodent model. METHODS: Twenty Sprague-Dawley rats were sensitized with intraperitoneal ovalbumin (OVA). Nasal inflammation was induced by the administration of intranasal OVA during consecutive days. The same procedure was performed in 20 control rats treated with saline solution. The allergic (AR) and non-allergic (NAR) rats were then randomized to nasal CPAP at 10 cm H2O for five hours or to sham CPAP. The degree of nasal inflammation was assessed by evaluating the percentage of neutrophils, eosinophils, basophils, and lymphocytes in the nasal mucosa. An unpaired Mann-Whitney test was used to analyze differences between groups. RESULTS: The greatest inflammation was observed in the group of AR without CPAP (1.24% ± 0.94%), followed by NAR with CPAP (0.64% ± 0.30%), AR with CPAP (0.64% ± 0.40%), and NAR without CPAP (0.21% ± 0.29%). CONCLUSIONS: Administration of nasal CPAP or allergy sensitization can produce, individually, neutrophil extravasation on the nasal mucosa of a rat model. The application of both stimuli is not responsible for increased inflammation. Therefore, this study suggests that rhinitis is not a major limitation for CPAP administration.

Fructose consumption impairs serotonergic signaling in the murine enteric nervous system.

The intake of free fructose has increased substantially since the development of high-fructose corn syrup. This has not only been associated with metabolic disorders but recent evidence also indicates that chronic fructose consumption can affect neuronal and cognitive function. In this study we investigated the effects of fructose consumption on serotonergic signaling and neuronal activity in the mouse submucous plexus. Male mice were put on a control or fructose (23% solution) diet for 6 weeks or were assigned to a recovery group that received normal water (2 weeks) after 4 weeks of fructose. At the end of the diet, gene expressions and enteric neuronal activity, after depolarization with high K(+) and 5-HT, were measured using Ca(2+) imaging and RT-qPCR, respectively. Even in the lack of gain weight and the absence of changes in duodenal permeability, the total number of 5-HT-responding neurons and the depolarization and 5-HT-evoked Ca(2+) amplitudes were significantly lower after fructose consumption. Expression of synaptobrevin CaV 2.1 and CaV 2.2 mRNA did not differ after fructose intake; however, CaV 2.1 mRNA levels were significantly higher in the recovery animals. SERT mRNA concentration, isolated from submucosal plexus containing mucosal epithelium, was significantly decreased after fructose consumption. Chronic fructose consumption impairs serotonergic signaling in the mouse submucous plexus, prior to weight gain and detectable intestinal permeability problems.

Localization and expression of TRPV1 and TRPA1 in the human oropharynx and larynx.

BACKGROUND: Previous studies have found that TRPV1 and TRPA1 receptor agonists improve swallow response in patients with oropharyngeal dysphagia (OD), but little is known about the expression of these receptors in the human oropharynx. The aim of this study was to assess the expression and localization of TRPV1 and TRPA1 in human samples from the oropharynx of healthy patients, to provide the basis for new pharmacological treatments for OD. METHODS: Samples from oropharyngeal regions innervated by cranial nerves V, IX, and X (tongue, pharynx, and epiglottis) were obtained during ENT surgery and processed either for mRNA (21 patients) or for immunohistochemical assays (seven patients). The expression analysis was performed with RT-qPCR using ACTBh as reference gene. Hemotoxylin and eosin staining was used to study the histology; the immunohistochemical assay used (i) neuron-specific enolase to detect nerve fibers or (ii) fluorescent probes to locate TRPV1 and TRPA1. RESULTS: TRPV1 was expressed in the three studied regions, with higher levels in CN V region (tongue) than in CN X region (epiglottis; p < 0.05), and was localized at epithelial cells and nociceptive fibers in all studied regions. TRPA1 was also expressed in all studied regions, but was always localized below the basal lamina. No immunoreactivity for TRPA1 was found on epithelial cells. CONCLUSIONS & INFERENCES: TRPV1 and TRPA1 are widely expressed in the human oropharynx with two distinct patterns. Our study further confirms that TRPV1/A1 receptors are promising therapeutic targets to develop active treatments for OD patients.

The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients.

BACKGROUND: Antireflux therapy may lead to recovery of impaired mucosal integrity in gastro-esophageal reflux disease (GERD) patients as reflected by an increase in baseline impedance. The study objective was to evaluate the effect of endoscopic fundoplication and proton pump inhibitor (PPI) PPI therapy on baseline impedance and heartburn severity in GERD patients. METHODS: Forty-seven GERD patients randomized to endoscopic fundoplication (n = 32) or PPI therapy (n = 15), and 29 healthy controls were included. Before randomization and 6 months after treatment, baseline impedance was obtained during 24-h pH-impedance monitoring. Heartburn severity was evaluated using the GERD-HRQL questionnaire. KEY RESULTS: Before treatment, baseline impedance in GERD patients was lower than in healthy controls (p < 0.001). Antireflux therapy increased baseline impedance (from 1498 [IQR 951-2472] to 2393 [IQR 1353-3027] Ω, p = 0.001), however it only led to a partial recovery when compared to healthy controls (2393 [IQR 1353-3027] vs 2983 [2335-3810] Ω, p < 0.01). The effect of both treatment options was not significantly different (p = 0.13) despite the increased number of non-acid reflux events in the PPI group. No correlation was found between baseline impedance and GERD symptoms before or after treatment. CONCLUSIONS & INFERENCES: Reduction in acid reflux by endoscopic fundoplication or PPI therapy leads to an increase in baseline impedance in GERD patients, likely to reflect recovery of mucosal integrity. The impact of non-acid reflux events on esophageal mucosal integrity may be limited as no difference in the increase in baseline impedance was observed after both treatment options. The lack of association between impedance baseline and heartburn severity indicates that other factors may contribute to heartburn perception in GERD.

Effect of baclofen on the acid pocket at the gastroesophageal junction.

Previous studies established that a pocket of highly acidic gastric juice is present postprandially at the gastroesophageal junction in man. The GABA-B agonist baclofen inhibits postprandial reflux events through its effects on the lower esophageal sphincter (LES). The aim of the current study was to investigate whether baclofen would affect the location and the extent of the postprandial acid pocket in healthy volunteers. Twelve healthy volunteers underwent acid pocket studies on two different occasions, at least 1 week apart. LES position was determined preprandially with pull-through manometry. Dual pH electrode and manometry probe stepwise pull-through (1 cm/minute, LES-10 to +5 cm) was performed at 30-minute intervals for 150 minutes, with administration of placebo or baclofen 40 mg after the first and ingestion of a liquid meal after the second pull-through. After placebo, a significant drop in intragastric gastric pH was present at the gastroesophageal junction after the meal, reflecting the acid pocket, and this was associated with a drop in LES pressure. Baclofen did not affect the presence of the acid pocket, but prevented the postprandial drop in LES pressure, and the extent of the acid pocket above the upper margin of the manometrically located LES was significantly decreased by baclofen (1.6 ± 0.7 vs. 0.3 ± 0.4 cm at 60 minutes, 2.2 ± 0.6 vs. 0.2 ± 0.6 at 90 minutes, and 1.5 ± 0.5 vs. 0.7 ± 0.7 cm at 120 minutes, all P < 0.05). Baclofen does not alter the intragastric acid pocket, but limits its extension into the distal esophagus, probably through an increase in postprandial LES pressure.

Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non-erosive reflux disease.

BACKGROUND: Non-erosive reflux disease (NERD) patients generally present with heartburn as the main symptom. Antidepressants might help to relieve heartburn by acting on the esophagus-brain axis. We aimed to assess the effect of nortriptyline on behavioral and brain responses to painful esophageal acid infusion in NERD patients evaluated with functional magnetic resonance imaging (fMRI). METHODS: In a randomized double-blind crossover design, 20 NERD patients off proton pump inhibitors (36.1 ± 9.3 years, 75% women) were assigned to 21 days of nortriptyline and placebo, in counterbalanced order, with a 21 days washout period in between both treatment periods. Changes in acid-induced brain response on fMRI and heartburn perception were assessed and at the end of each treatment. KEY RESULTS: Nortriptyline significantly reduced the acid-induced brain response in prefrontal cortex (median [IQR]: -1.9 [-4.5 to -0.1] vs -0.3 [-2.5 to 2.3]; p = 0.050), caudate (-3.0 [-5.1 to -0.01] vs 0.48 [-1.9 to 3.1]; p = 0.029), insula (-2.4 [-4.8 to -0.6] vs -0.2 [-1.5 to 1.5]; p = 0.029), cingulate (-4.2 [-8.8 to -0.1] vs -0.6 [-1.8 to 3.0]; p = 0.017), and hippocampus (-2.7 [-6.0 to 0.5] vs -0.04 [-2.3 to 1.9]; p = 0.006) in comparison with placebo. However, there was no significant difference between nortriptyline and placebo in clinical outcomes and side effects. CONCLUSIONS & INFERENCES: Nortriptyline decreased the brain response to esophageal acid infusion more markedly than placebo, but without clinical significance.

Postprandial symptoms originating from the stomach in functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is characterized by chronic epigastric symptoms. The stomach has been held responsible for the generation of symptoms, but the latest reports have pointed out that also the duodenum can be implicated in the pathophysiology. The aim of this study was to elucidate which dyspeptic symptoms originate from the stomach and/or from the small intestine after a meal. METHODS: Two hundred eighty-four FD patients underwent a gastric emptying breath test. Breath samples were taken and the intensity of six dyspeptic symptoms (fullness, bloating, belching, nausea, epigastric burning, and epigastric pain) was scored before a meal and at 15 min intervals for a period of 240 min postprandially. Time curves of each symptom were analyzed and severity scores during the gastric and the intestinal phase were compared. KEY RESULTS: Time curves of fullness, bloating, belching, and nausea displayed a significant negative slope, while symptom severity of epigastric burning and epigastric pain did not decrease over time. Numerical analysis revealed that scores for fullness, bloating, and belching were higher during the gastric phase compared with the intestinal phase. On the other hand, intensities of nausea, epigastric burning, and epigastric pain were similar during both phases. CONCLUSIONS & INFERENCES: Intensities of fullness, bloating, and belching decrease with food moving from the stomach to the small intestine indicating that the stomach plays a crucial role in the generation of these symptoms. In contrast, the symptom severity of epigastric burning and epigastric pain persists with progression of food to the small intestine.

Pathophysiology of gastro-esophageal reflux disease: a role for mucosa integrity?

BACKGROUND: Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. PURPOSE: This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed.

Role of duodenal mucosal nerve endings in the acid-induced duodenogastric sensorimotor reflex: effect of benzocaine in healthy humans.

BACKGROUND: Duodenal acid exposure induces a duodenogastric reflex resulting in gastric relaxation, inhibition of antral motility, and sensitization of the proximal stomach to distension. Duodenal hypersensitivity to acid has been identified as a potential pathogenic mechanism in functional dyspepsia. The nature and localization of the duodenal acid-sensitive receptors are still elusive. We hypothesize that acid directly activates superficial afferent nerve endings in the duodenal mucosa, triggering the duodenogastric reflex. METHODS: In a double-blind, randomized, crossover study in 13 healthy volunteers, benzocaine, a local anesthetic, vs saline was perfused in the duodenum 15 min before duodenal acid perfusion. Gastric responses were monitored by a barostat. Stepwise isobaric gastric distensions were performed before and during acid perfusion. Symptoms were evaluated by visual analogue scales for six dyspeptic symptoms and an overall perception score. KEY RESULTS: Benzocaine perfusion caused a relaxation of the stomach prior to duodenal acidification, indicating the existence of an excitatory duodenogastric tone. Pretreatment of the duodenum with benzocaine reduced the acid-induced gastric relaxation by 50% and abolished the inhibition of phasic motility of the proximal stomach. Finally, sensitization to distension was more pronounced in the benzocaine condition because of higher proximal gastric volumes. CONCLUSIONS & INFERENCES: These findings support a model in which different neuronal subpopulations are responsible for the motor and sensory limb of the acid-sensitive duodenogastric reflex, making benzocaine an unsuitable drug to treat duodenal hypersensitivity to acid. These data provide more insight in the contribution of duodenal neuronal input to gastric physiology in the fasting state.

Local micromechanical properties of decellularized lung scaffolds measured with atomic force microscopy.

Bioartificial lungs re-engineered from decellularized organ scaffolds are a promising alternative to lung transplantation. Critical features for improving scaffold repopulation depend on the mechanical properties of the cell microenvironment. However, the mechanics of the lung extracellular matrix (ECM) is poorly defined. The local mechanical properties of the ECM were measured in different regions of decellularized rat lung scaffolds with atomic force microscopy. Lungs excised from rats (n=11) were decellularized with sodium dodecyl sulfate (SDS) and cut into ~7µm thick slices. The complex elastic modulus (G(∗)) of lung ECM was measured over a frequency band ranging from 0.1 to 11.45Hz. Measurements were taken in alveolar wall segments, alveolar wall junctions and pleural regions. The storage modulus (G', real part of G(∗)) of alveolar ECM was ~6kPa, showing small changes between wall segments and junctions. Pleural regions were threefold stiffer than alveolar walls. G' of alveolar walls and pleura increased with frequency as a weak power law with exponent 0.05. The loss modulus (G″, imaginary part of G(∗)) was 10-fold lower and showed a frequency dependence similar to that of G' at low frequencies (0.1-1Hz), but increased more markedly at higher frequencies. Local differences in mechanical properties and topology of the parenchymal site could be relevant mechanical cues for regulating the spatial distribution, differentiation and function of lung cells.

Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health.

BACKGROUND: Menthol reduces intestinal motility in animal studies, an effect that is probably mediated by transient receptor potential channels. Peppermint oil (PO), with menthol as a major constituent, is widely used as a spasmolytic agent in irritable bowel syndrome. In the current study, we investigated the effect of acute PO administration on intragastric pressure (IGP) profiles and gastric sensorimotor functions in health. METHODS: Healthy volunteers underwent IGP measurement before and during continuous intragastric infusion of a nutrient drink (n = 13), and gastric barostat studies (n = 13). A single capsule of PO (182 mg) or placebo was administered during the studies in a randomized controlled crossover design. Throughout the studies, healthy volunteers scored 11 epigastric symptoms on a visual analogue scale (VAS); satiation was scored on a 6-point Likert scale during intragastric infusion. KEY RESULTS: During fasting, IGP and motility index (MI) of the proximal stomach decreased significantly after PO administration compared with placebo (P < 0.0001 and <0.05, respectively). In contrast, during intragastric infusion of the nutrient drink, no significant differences were detected between PO and placebo in IGP profiles, MI, satiation scores, and epigastric symptoms. The maximum infused volume, gastric compliance or sensitivity to balloon distention did not differ between both treatment arms. However, reduced appetite scores were seen during fasting after PO treatment, as compared with placebo (P = 0.01). Postprandial VAS scores were similar between PO and placebo. CONCLUSIONS & INFERENCES: Peppermint oil reduces IGP, proximal phasic contractility, and appetite, with negligible effects on gastric sensitivity, tone, accommodation, and nutrient tolerance in health.

Origin and modulation of circular smooth muscle layer contractions in the porcine esophagus.

BACKGROUND: The origin and modulation mechanisms controlling timing and amplitude of esophageal body peristalsis are not fully understood. We aimed to characterize the neurotransmitters involved in the origin and modulation of circular smooth muscle esophageal body (EB) contractions. METHODS: Responses of porcine EB strips to electrical stimulation of motor neurons (MNs) were assessed in organ baths and with microelectrodes. The effect of antagonists of inhibitory (L-NAME 1 mmol L(-1) , MRS2179 10 µmol L(-1) ) and excitatory neurotransmitters (atropine 1 µmol L(-1) ; SR140333 1 µmol L(-1) -NK(1) ra-, GR94800 1 µmol L(-1) -NK(2) ra-) and of ganglionic neurotransmitters (hexamethonium 100 µmol L(-1) , ondansetron 1 µmol L(-1) , NF279 10 µmol L(-1) ) were characterized. KEY RESULTS: Electrical field stimulation (EFS) induced a frequency-dependent off-contraction (16.8 ± 0.8 g) following a latency period. Latency was significantly reduced by L-NAME (-66.1 ± 4.1%) and MRS2179 (-25.9 ± 5.6%), and strongly increased by atropine (+36.8 ± 5.8%). Amplitude was reduced by L-NAME (-69.9 ± 10.4%), MRS2179 (-34.1 ± 6.0%), atropine (-42.3 ± 4.7%), hexamethonium (-18.9 ± 3.3%), NF279 (-20.7 ± 3.5%), ondansetron (-16.3 ± 3.2%), GR94800 (-28.0 ± 4.8%) SR140333 (-20.9 ± 7.1%), and α-chymotrypsin (-31.3 ± 7.0%). The EFS induced a monophasic nitrergic inhibitory junction potential. CONCLUSIONS & INFERENCES: Our results suggest that timing (latency) and amplitude of esophageal contractions are determined by a balance of complex interactions between excitatory and inhibitory MNs. Latency depends on the activation of inhibitory MNs releasing NO and a minor purinergic contribution through P2Y(1) receptors, and excitatory MNs releasing ACh. Amplitude depends on a major contribution of excitatory MNs releasing ACh and tachykinins, and also on inhibitory MNs releasing NO, ATP or related purines, and peptidergic neurotransmitters acting as strong modulators of the excitatory neuroeffector transmission.

A double-blind sham-controlled study of the effect of radiofrequency energy on symptoms and distensibility of the gastro-esophageal junction in GERD.

OBJECTIVES: Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients treated with radiofrequency delivery (Stretta procedure) at the gastro-esophageal junction (GEJ), but the mechanism underlying this improvement is unclear. The objective of this study was to test the hypothesis that Stretta alters GEJ resistance. METHODS: We conducted a double-blind randomized cross-over study of Stretta and sham treatment. Consecutive GERD patients were included in the study. The study was conducted in a tertiary care center. Patients underwent two upper gastrointestinal endoscopies with 3 months interval, during which active or sham Stretta treatment was performed in a randomized double-blind manner. Symptom assessment, endoscopy, manometry, 24-h esophageal pH monitoring, and a distensibility test of the GEJ were done before the start of the study and after 3 months. RESULTS: Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measure. In all, 22 GERD patients (17 females, mean age 47±12 years) participated in the study; 11 in each group. Initial sham treatment did not affect any of the parameters studied. Three months after initial Stretta procedure, no changes were observed in esophageal acid exposure and lower esophageal sphincter (LES) pressure. In contrast, symptom score was significantly improved and GEJ compliance was significantly decreased. Administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-Stretta level, arguing against GEJ fibrosis as the underlying mechanism. CONCLUSIONS: The limitation of this study was reflux evaluation did not include impedance monitoring. In this sham-controlled study, Stretta improved GERD symptoms and decreased GEJ compliance. Decreased GEJ compliance, which reflects altered LES neuromuscular function, may contribute to symptomatic benefit by decreasing refluxate volume.

The effect of spontaneous breathing on systemic interleukin-6 during ventilator weaning.

During the weaning process, spontaneous breathing trials (SBTs) involve cardiopulmonary stress for ventilated patients. As interleukin (IL)-6 is a major modulator of the stress response, we hypothesised that systemic IL-6 increases during a SBT and that this increase is more evident in SBT failure. 49 SBTs of 30-min duration were performed on different mechanically ventilated patients, and classified as SBT failure or success. Blood samples were drawn before and at the end of the SBT. An additional sample was drawn 24 h later in a subset of patients (n = 39). Serum IL-6 levels and other inflammatory mediators commonly associated with stress were determined. IL-6 levels increased from mechanical ventilation to spontaneous breathing in all patients (p = 0.02) and in the chronic obstructive pulmonary disease (COPD) population (p = 0.05) with SBT failure compared with success, but not in non-COPD patients (p = 0.12). After 24 h of SBT stress, IL-6 levels decreased in patients with SBT failure (under mechanical ventilation at that point) (p = 0.02) and those with weaning success (p = 0.04). No changes were observed in the remaining inflammatory mediators. Systemic IL-6 increases during a 30-min, failed SBT, especially in COPD patients. Future studies may corroborate the different IL-6 responses among different populations who initiate weaning, together with the potential clinical implications.

Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers.

There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean ± standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility.