RESUMEN
BACKGROUND: Administration of a bitter compound can alter the intragastric pressure (IGP) after a meal. Additionally, a negative correlation between IGP and the number of transient lower esophageal sphincter relaxations (TLESRs) has been demonstrated. However, the effect of a bitter tastant on the number of TLESRs and subsequent reflux episodes has never been investigated and it is unclear whether bitter food items should be avoided in gastro-esophageal reflux disease. We hypothesize that bitter administration in healthy volunteers (HVs) will lead to an increase in the number of TLESRs. METHODS: After an overnight fast, 20 female HVs (36 years [21-63]) underwent a high-resolution impedance manometry (HRiM) measurement. After placement of the HRiM probe, 0.1 ml/kg of a 10 mM denatonium benzoate solution (bitter) or an identical volume of water (placebo) was administered directly into the stomach. The number of TLESRs and reflux episodes was quantified 30 min before and 2 h after consumption of a high caloric meal. KEY RESULTS: There was no significant difference in the number of TLESRs or reflux episodes between the bitter and placebo condition. Additionally, no differences were observed in the nature (gas or liquid) and extent of reflux events. Lower esophageal sphincter pressures dropped significantly in the first postprandial hour to start recovering slowly back to baseline values during the second postprandial hour (p < 0.0001), without any difference between both conditions. CONCLUSIONS & INTERFERENCES: Administration of the bitter tastant denatonium benzoate has no influence on the number of TLESRs or reflux episodes.
Asunto(s)
Agentes Aversivos/farmacología , Esfínter Esofágico Inferior/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Compuestos de Amonio Cuaternario/farmacología , Gusto/fisiología , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Reflujo Gastroesofágico , Voluntarios Sanos , Humanos , Persona de Mediana Edad , Peristaltismo/efectos de los fármacosRESUMEN
BACKGROUND: Drugs such as citalopram, "targeting" the serotonin pathway, can alter esophageal mechano-chemical sensitivity and gastrointestinal motility. The aim of this study was to clarify the effect of citalopram on esophageal motility and sphincter function, transient lower esophageal sphincter relaxations (TLESRs), and reflux events. METHODS: Sixteen healthy volunteers (HV) receiving 20 mg citalopram or placebo intravenously, in a randomized cross-over fashion, underwent two high-resolution impedance manometry studies involving liquid swallows and a high-fat, high-caloric meal. Manometric, reflux, and symptom-related parameters were studied. KEY RESULTS: A lower distal contractile integral was recorded under citalopram, compared with placebo (P = 0.026). Upper esophageal sphincter (UES) resting pressure was significantly higher after citalopram administration throughout the study (P < 0.05, all periods). Similarly, the UES postswallow mean and maximum pressures were higher in the citalopram condition (P < 0.0001, in both cases) and this was also the case for the 0.2 s integrated relaxation pressure (P = 0.04). Esophagogastric junction resting pressures in the citalopram visit were significantly higher during swallow protocol, preprandial period, and the first postprandial hour (P < 0.05, in all cases). TLESRs and total reflux events were both reduced after citalopram infusion (P = 0.01, in both cases). During treatment with citalopram, five participants complained about globus sensation (P = 0.06). This citalopram-induced globus was associated with higher UES postswallow mean and maximum pressure values (P = 0.01 and P = 0.04, respectively). CONCLUSIONS AND INFERENCES: Administration of citalopram exerts a diversified response on esophageal motility and sphincter function, linked to clinically relevant phenomena: a reduction in postprandial TLESRs and the induction of drug-induced globus.
Asunto(s)
Citalopram/farmacología , Unión Esofagogástrica/efectos de los fármacos , Esófago/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Trastornos de Deglución/fisiopatología , Femenino , Reflujo Gastroesofágico/fisiopatología , Globo Faríngeo/fisiopatología , Voluntarios Sanos , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to investigate the frequency and circadian changes in transient lower esophageal sphincter relaxations (TLESRs) in normal volunteers using 24-hour high-resolution impedance manometry (HRIM). METHODS: Fifteen volunteers underwent HRIM. TLESRs were recorded during the mealtime, 2-hour postprandial, daytime, and supine periods. The catheter was firmly secured to the nose, and subjects went home, ate normal meals, and continued routine daily activities. KEY RESULTS: Successful recordings were obtained in 11 volunteers. Overall, 1083 TLESRs were documented; the average occurrence was 4.2/h, and the duration was 21.0 ± 5.2 seconds. The majority of the TLESRs occurred during the 2-hour postprandial (42.7%) and daytime (31.5%) periods, while 10.2% and 15.6% occurred during the mealtime and supine periods, respectively. Eight hundred and eighty-six (81.8%) TLESRs were associated with reflux. Overall, 25.5% of TLESRs were preceded by partial secondary peristalsis (PSP), while 74.5% were preceded by nothing. Terminating events included primary peristalsis (PP; 40.3%), PSP (42.8%), full secondary peristalsis (FSP; 8.2%), or nothing (8.7%). Both preceding and terminating events periodically changed throughout the four periods. One hundred and twelve (10.3%) TLESRs with both preceding and terminating events of PSP, presenting as a "mirror phenomenon," were documented. The majority of these TLESRs occurred during the supine (70.5%). CONCLUSIONS & INFERENCES: Transient lower esophageal sphincter relaxations are common physiological motor events in normal volunteers; these events have certain circadian rhythms, as do the events that precede and terminate TLESR events. A special "mirror phenomenon" is observed when both the preceding and terminating events are PSP.
Asunto(s)
Esfínter Esofágico Inferior/fisiopatología , Manometría/métodos , Adulto , Ritmo Circadiano , Femenino , Voluntarios Sanos , Humanos , Masculino , Monitoreo Fisiológico , Relajación Muscular , Periodo Posprandial , Valores de Referencia , Posición Supina , Adulto JovenRESUMEN
The pathogenesis of gastroesophageal reflux disease (GERD) is complex and involves changes in reflux exposure, epithelial resistance, and visceral sensitivity. The gastric refluxate is a noxious material that injures the esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the primary determinant of disease severity. This exposure arises via compromise of the anti-reflux barrier and reduced ability of the esophagus to clear and buffer the refluxate, leading to reflux disease. However, complications and symptoms also occur in the context of normal reflux burden, when there is either poor epithelial resistance or increased visceral sensitivity. Reflux therefore develops via alterations in the balance of aggressive and defensive forces.
Asunto(s)
Esfínter Esofágico Inferior/fisiopatología , Jugo Gástrico/fisiología , Mucosa Gástrica/metabolismo , Reflujo Gastroesofágico/etiología , Infecciones por Helicobacter/complicaciones , Ansiedad/complicaciones , Depresión/complicaciones , Mucosa Esofágica/fisiopatología , Esfínter Esofágico Inferior/inervación , Esofagitis Péptica , Reflujo Gastroesofágico/diagnóstico , Helicobacter pylori/aislamiento & purificación , Hernia Hiatal/complicaciones , Humanos , Manometría , Obesidad/complicaciones , Obesidad/fisiopatología , Índice de Severidad de la Enfermedad , Estrés Psicológico/complicacionesRESUMEN
BACKGROUND & AIMS: Central obesity promotes gastroesophageal reflux, which may be related to increased intra-abdominal pressure. We investigated the effect of increasing abdominal pressure by waist belt on reflux in patients with reflux disease. METHODS: We performed a prospective study of patients with esophagitis (n = 8) or Barrett's esophagus (n = 6); median age was 56 years and median body mass index was 26.8. Proton pump inhibitors were stopped at least 7 days before the study and H2 receptor antagonists were stopped for at least 24 hours before. The severity of upper GI symptoms was assessed and measurements of height, weight, and waist and hip circumference taken. Combined high-resolution pH measurement and manometry were performed in fasted state for 20 minutes and for 90 minutes following a standardized meal. The squamocolumnar junction was marked by endoscopically placed radiopaque clips. The procedures were performed with and without a waist belt (a weight-lifter belt applied tightly and inflated to a constant cuff pressure of 50 mmHg). We compared variables between groups using the Wilcoxon Signed Rank test and tested for correlations using Spearman Rho bivariate analysis. RESULTS: Without the belt, intragastric pressure correlated with waist circumference (r = 0.682; P = .008), with the range in pressure between smallest and largest waist circumference being 15 mmHg. The belt increased intragastric pressure by a median of 6.9 mmHg during fasting (P = .002) and by 9.0 mmHg after the meal (P = .001). Gastroesophageal acid reflux at each of the pH sensors extending 5.5 cm proximal to the peak lower esophageal sphincter pressure point was increased by approximately 8-fold by the belt (all P < .05). Following the meal, the mean number of reflux events with the belt was 4, vs 2 without (P = .008). Transient lower esophageal sphincter relaxations were not increased by the belt, but those associated with reflux were increased (2 vs 3.5; P = .04). The most marked effect of the belt was impaired esophageal clearance of refluxed acid (median values of 23.0 seconds without belt vs 81.1 seconds with belt) (P = .008). The pattern of impaired clearance was that of rapid re-reflux after peristaltic clearance. CONCLUSIONS: In a prospective study of patients with esophagitis or Barrett's esophagus, we found belt compression increased acid reflux following a meal. The intragastric pressure rise inducing this effect is well within the range associated with differing waist circumference and likely to be relevant to the association between obesity and reflux disease.
Asunto(s)
Esófago de Barrett/etiología , Vestuario/efectos adversos , Esofagitis/etiología , Esófago/fisiopatología , Reflujo Gastroesofágico/etiología , Obesidad Abdominal/complicaciones , Adulto , Anciano , Esófago de Barrett/diagnóstico , Esófago de Barrett/fisiopatología , Índice de Masa Corporal , Constricción , Endoscopía Gastrointestinal , Monitorización del pH Esofágico , Esofagitis/diagnóstico , Esofagitis/fisiopatología , Femenino , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/fisiopatología , Humanos , Masculino , Manometría , Persona de Mediana Edad , Obesidad Abdominal/diagnóstico , Valor Predictivo de las Pruebas , Presión , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Circunferencia de la Cintura , Adulto JovenRESUMEN
Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.
RESUMEN
BACKGROUND: Gastro-esophageal reflux (GER), the retrograde flow of gastric contents into the esophagus is a physiologic phenomenon, which can evoke symptoms and/or lesions in the esophagus (=gastro-esophageal reflux disease or GERD). Proton pump inhibitors (PPIs) reduce gastric acidity; however, as they are unable to control transient lower esophageal sphincter relaxations (TLESRs), the main mechanism for reflux in GERD, they do not abolish reflux. TLESRs occur predominantly in the postprandial period, and they are believed to be triggered by gastric distention. Gastric accommodation (GA) is the physiologic response to gastric distention and serves to prevent a rise in gastric wall tension during food intake. We aimed to study the relationship between GA and TLESRs, as they both are triggered by gastric distention. METHODS: We studied 12 GERD patients (average age 37 years [range 18-62], 7m/5f) and nine healthy volunteers (average age 27 years [range 22-36], 2m/7f) using high resolution manometry-impedance measurement before and after a mixed meal challenge. We determined the number of TLESRs (with or without reflux) and measured pre- and postprandial IGP. The change in IGP between the pre- and postprandial period (ΔIGP) is used as surrogate for GA. We also measured LES pressure before and after the meal and calculated the change (ΔLESp). KEY RESULTS: There were no statistical differences between pre- and postprandial IGP in GERD and healthy volunteers and similarly, there was no significant difference between pre- and postprandial LES pressures in GERD patients and healthy volunteers. The number of TLESRs (with or without reflux) was similar in GERD and healthy volunteers. More importantly, we did observe a negative correlation between ΔIGP and the number of TLESRs, irrespective of whether they were associated with reflux or not, in the GERD patients (without reflux r = -0.67, p = 0.017; with reflux r = -0.81, p = 0.0014). The same observations were found in healthy volunteers, where ΔIGP and the number of TLESRs are significantly inversely correlated (without reflux r = -0.87, p = 0.0045; with reflux r = -0.75, p = 0.021). We could not establish a correlation between ΔLESp and the number of TLESRs, neither in GERD patients nor in healthy volunteers. CONCLUSIONS & INFERENCES: This is the first study showing a clear negative correlation between ΔIGP and the number of TLESRs, irrespective of whether they were associated with reflux or not, both in GERD patients and in healthy subjects. These results suggest that TLESRs and GA are closely linked, probably through activation of mechanoreceptors involved in triggering of TLESRs.
Asunto(s)
Esfínter Esofágico Inferior/fisiopatología , Reflujo Gastroesofágico/fisiopatología , Motilidad Gastrointestinal , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial/fisiología , Adulto JovenRESUMEN
BACKGROUND & AIMS: In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma. METHODS: We performed a study of 24 healthy, Helicobacter pylori-negative volunteers with a small WC and 27 with a large WC. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. RESULTS: The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). CONCLUSIONS: Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.
Asunto(s)
Cardias/patología , Reflujo Gastroesofágico/etiología , Obesidad/complicaciones , Circunferencia de la Cintura , Adulto , Anciano , Biopsia , Esfínter Esofágico Inferior/patología , Femenino , Determinación de la Acidez Gástrica , Humanos , Masculino , Manometría , Metaplasia , Persona de Mediana Edad , Membrana Mucosa/patología , Obesidad/patologíaRESUMEN
BACKGROUND: Differences in lower esophageal sphincter (LES) and peristaltic function and in transient LES relaxations (TLESR) have been described in patients with gastro-esophageal reflux disease (GERD). However, some of these differences may be the result of chronic GERD rather than being an underlying contributory factor. METHODS: Twins discordant for GERD symptoms, i.e., only one twin had GERD symptoms, underwent standard LES and esophageal body manometry, and then using a sleeve sensor prolonged LES and pH monitoring, 30 min before and 60 min after a 250 mL 1200 kcal lipid meal. KEY RESULTS: Eight monozygotic and 24 dizygotic female twins were studied. Although there was no difference in preprandial LES pressure (symptomatic 13.2 ± 7.1 mmHg vs asymptomatic 15.1 ± 6.2 mmHg, P = 0.4), LES pressure fell further postprandially in symptomatic twins (LES pressure area under the curve 465 ± 126 vs 331 ± 141 mmHg h, P < 0.01). 12/37 (32%) of acid reflux episodes in symptomatic twins occurred due to low LES pressure or deep inspiration/strain and 0/17 in asymptomatic twins (P = 0.01). There was no difference between symptomatic and asymptomatic twins in: peristaltic amplitude, ineffective esophageal body motility, hiatus hernia prevalence, or LES length. There was also no difference in TLESR frequency preprandially (symptomatic median 1(range 0-2) vs asymptomatic 0(0-2), P = 0.08) or postprandially (2.5(1-8) vs 3(1-6), P = 0.81). CONCLUSIONS & INFERENCES: Twins with GERD symptoms had lower postprandial LES pressure and given the close genetic link between the twins, it is possible that such differences are caused by GERD. Acid reflux episodes associated with a hypotensive LES were seen in symptomatic, but not in asymptomatic twins.