Acid Perfusion Research Articles

Epithelial barrier integrity and intraluminal nitric oxide production in response to acid perfusion of the ferret oesophagus

To evaluate the source and role of acid-induced intraluminal nitric oxide (NO) production in the oesophagus by studying how the exposure of the oesophagus to acid affects NO release, via the NO-producing enzyme NO synthase and its relation to changes in epithelial barrier integrity. Ferrets were anaesthetized and their oesophagi were divided at both ends. The test subjects were pre-treated with the intravenous NO synthase inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME, 100 mg kg(-1)) and 1400W (12 mg kg(-1)). Untreated and N(G)-nitro-D-arginine-methyl ester pre-treated (D-NAME, 100 mg kg(-1)) animals served as controls. The oesophagus was then perfused with either HCl (0.1 m) or physiological saline for 20 min. The intraluminal NO concentration was determined before and after the acid/saline infusion while the transmucosal potential difference (PD) was monitored continuously. Oesophageal biopsies were examined for expression of inducible NO synthase using immunohistochemistry. The intraluminal NO concentration increased after acid exposure. This was blocked by L-NAME and 1400W, but not by D-NAME. The peak PD response was not affected by agents affecting NO synthesis, while the plateau response was attenuated by L-NAME, D-NAME and 1400W. Immunohistochemistry revealed inducible NO synthase expression in the epithelium. Exposing the ferret oesophageal mucosa to acid elicited an increase in juxtamucosal NO formation through the activation of inducible NO synthase. The corresponding electrophysiological observations suggested an association between mucosal NO production and epithelial integrity.

Effect of repeated cycles of acute esophagitis and healing on esophageal peristalsis, tone, and length

Severe esophagitis is associated with motor abnormalities in the esophageal body and lower esophageal sphincter. Reflux disease involves repeated episodes of mucosal inflammation and spontaneous or treatment-induced healing. The aims of this study were 1) to further assess changes induced by acute esophagitis on esophageal peristalsis, tone, and shortening and 2) to assess the effect of repeated sequences of acute esophagitis-healing on these motor parameters. Experiments were performed on adult cats. Esophageal manometry and barostat were performed before, 24 h after, and every 7 days after intraesophageal acid perfusion (0.1 N HCl, 80 min). Esophageal length was measured during manometry, and compliance of the esophageal body was assessed with barostat. The identical protocol was performed 8 and 16 wk after the first acid perfusion. The degree of esophageal mucosal damage was evaluated by endoscopy, histopathology, and myeloperoxidase activity. Acid perfusion induced severe esophagitis. At 24 h, distal peristaltic contractions disappeared, lower esophageal sphincter pressure was reduced by 60%, the esophagus length was 1-2 cm shorter, and esophageal compliance was reduced by 30%. Most parameters recovered in 4 wk. Subsequent repeated acute injuries induced similar endoscopic esophagitis but a different pattern of inflammatory infiltration and fibrosis in the mucosa and muscle layers, resulting in milder motor disturbances. Acute experimental esophagitis provokes severe but reversible hypomotility. Spaced repeated acute injuries provoke milder motor effects, suggesting an adaptive response.

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.

Long-term outcome is worse after laparoscopic than after conventional Nissen fundoplication

Objective. No long-term studies of laparoscopic and open fundoplication were available in 1994. The aim of this study was to compare reflux control and side effects after laparoscopic and open fundoplication. Material and methods. Adult patients with uncomplicated gastro-oesophageal reflux disease were included in this prospective randomized clinical trial between laparoscopic and open 360° fundoplication. Patients with uncomplicated gastro-oesophageal reflux disease were included with the exception of those with weak peristalsis or suspected short oesophagus. Two senior surgeons, well trained in laparoscopic antireflux surgery, performed the 45 laparoscopic operations. Forty-eight patients underwent open surgery performed or supervised by two other senior surgeons, also well trained in gastro-oesophageal surgery. One of the latter recruited all the patients. Manometry and 24-h oesophageal pH monitoring were performed before operation and 6 months postoperatively. Manometry also included a short-term reflux test, an acid clearing test and an acid perfusion test. Symptom evaluation was performed before surgery, 6 moths after and at long-term follow-up (33–79 months postoperatively) by the same surgeon. Long-term follow-up also included endoscopy. Results. Six months after laparoscopy 4 patients had disabling dysphagia. None of the patient had disabling dysphagia after laparotomy. Four patients had mild heartburn 6 months after laparoscopy and 2 patients after laparotomy. Between 6 months’ follow-up and long-term follow-up, 6 patients were reoperated on in the laparoscopy group and 2 patients in the laparotomy group. Three patients operated on with laparotomy had died of intercurrent diseases. After laparoscopy, at long-term follow-up, 62% of patients (28/45) were satisfied compared with 91% (41/45) after laparotomy. The difference was significant (p<0.01). Conclusions. Early postoperative reflux control was similar for laparoscopic and conventional fundoplication. At long-term follow-up significantly more patients were satisfied after laparotomy than after laparoscopy.

Scatter and cross-talk correction for one-day acquisition of123i-bmipp and99mtc-tetrofosmin myocardial spect

123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TET) are widely used for evaluation of myocardial fatty acid metabolism and perfusion, respectively. ECG-gated TET SPECT is also used for evaluation of myocardial wall motion. These tests are often performed on the same day to minimize both the time required and inconvenience to patients and medical staff. However, as 123I and 99mTc have similar emission energies (159 keV and 140 keV, respectively), it is necessary to consider not only scattered photons, but also primary photons of each radionuclide detected in the wrong window (cross-talk). In this study, we developed and evaluated the effectiveness of a new scatter and cross-talk correction imaging protocol. Fourteen patients with ischemic heart disease or heart failure (8 men and 6 women with a mean age of 69.4 yr, ranging from 45 to 94 yr) were enrolled in this study. In the routine one-day acquisition protocol, BMIPP SPECT was performed in the morning, with TET SPECT performed 4 h later. An additional SPECT was performed just before injection of TET with the energy window for 99mTc. These data correspond to the scatter and cross-talk factor of the next TET SPECT. The correction was performed by subtraction of the scatter and cross-talk factor from TET SPECT. Data are presented as means +/- S.E. Statistical analyses were performed using Wilcoxon's matched-pairs signed-ranks test, and p < 0.05 was considered significant. The percentage of scatter and cross-talk relative to the corrected total count was 26.0 +/- 5.3%. EDV and ESV after correction were significantly greater than those before correction (p = 0.019 and 0.016, respectively). After correction, EF was smaller than that before correction, but the difference was not significant. Perfusion scores (17 segments per heart) were significantly lower after as compared with those before correction (p < 0.001). Scatter and cross-talk correction revealed significant differences in EDV, ESV, and perfusion scores. These observations indicate that scatter and cross-talk correction is required for one-day acquisition of 123I-BMIPP and 99mTc-tetrofosmin SPECT.

Sensory testing of the esophagus.

Originally, sensory testing of the esophagus included the acid perfusion test and the edrophonium test, which were developed to assess patients with non-cardiac chest pain. In the last 2 decades interest in functional esophageal disorders has increased and thus further understanding of the underlying mechanisms of esophageal pain required development of new sensory testing techniques. Balloon distension using a computerized electronic device, electrical stimulation and impedance planimetry have generated important information about esophageal sensory thresholds for pain in different disease states. Intraluminal ultrasonography has been used to determine the physiologic changes of the muscle wall of the esophagus during perception of typical esophageal symptoms. Central evaluation of patients undergoing esophageal stimulation has recently been introduced to assess cerebral activation in different esophageal disorders. However, many studies using esophageal sensory testing are afflicted with significant design flaws, making interpretation of the results very difficult. This is primarily due to lack of recognition of factors that can modulate esophageal sensation.

Proinflammatory cytokines alter/reduce esophageal circular muscle contraction in experimental cat esophagitis.

Cholinergic mechanisms are largely responsible for esophageal contraction in response to swallowing or to in vitro electrical field stimulation (EFS). After induction of experimental esophagitis by repeated acid perfusion, the responses to swallowing and to EFS were significantly reduced but contraction in response to ACh was not affected, suggesting that cholinergic mechanisms are damaged by acid perfusion but that myogenic mechanisms are not. Measurements of ACh release in response to EFS confirmed that release of ACh was reduced in esophagitis compared with normal controls. To examine factors contributing to this neuropathy, normal esophageal strips were incubated for 1-2 h with the proinflammatory cytokines IL-1beta (100 U/ml), IL-6 (1 ng/ml), or TNF-alpha (1 ng/ml). IL-1beta and IL-6 levels, measured by Western blot analysis, increased in esophagitis compared with normal circular muscle. IL-1beta and IL-6 reduced contraction in response to EFS (2-10 Hz, 0.2 ms) but did not affect ACh-induced contraction, suggesting that these cytokines inhibit ACh release without affecting myogenic contractile mechanisms. EFS-induced ACh release was significantly reduced in normal esophageal strips by incubation in IL-1beta or IL-6, suggesting that they may contribute to the contractility changes. TNF-alpha at 1 ng/ml, however, did not affect the response to ACh or to electrical stimulation but inhibited both at higher concentrations. TNF-alpha levels were low in normal muscle and did not increase with esophagitis. The data suggest that the proinflammatory cytokines IL-1beta and IL-6 contribute to reduced esophageal contraction by inhibiting release of ACh from myenteric neurons.

Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases.

Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. To investigate oesophageal hypersensitivity in Japanese NERD patients. We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 +/- 3.4, 4.4 +/- 3.4, 27.8 +/- 26.7, respectively) were higher than in erosive GERD (3.2 +/- 3.3, 3.0 +/- 3.2, 18.2 +/- 24.8) and Barrett patients (2.5 +/- 4.0, 1.8 +/- 3.3, 15.0 +/- 28.8), and significantly higher than in the control group (1.7 +/- 2.7, 1.1 +/- 2.0, 5.4 +/- 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Suprarenal fixation of endograft in abdominal aortic aneurysm treatment: focus on renal function.

The objective of this work was to evaluate any variation of renal function detected by renal scintigraphy after the suprarenal fixation of endografts for abdominal aortic aneurysm (AAA) repair. In the few articles that have considered this problem, renal function was evaluated only by biochemical tests, which are inadequate in demonstrating small changes in renal function and in appreciating the worsening of a single kidney's function. Between April 1999 and May 2002, 47 patients with an inappropriate infrarenal proximal neck had a suprarenal fixation for AAA. To assess renal function, a technetium-99m diethylene triamine penta-acetic acid (TC-DTPA) perfusion scintigraphy was performed preoperatively on the third postoperative day and at 6, 12 months, and then yearly thereafter. Worsening of renal function was defined as a decrease of glomerular filtration rate (GFR) > or =20% (detected with Gates method). Serum creatinine level was tested preoperatively and at the first and third postoperative day. Endograft deployment was technically successful in 44 patients (93.6%); clinical perioperative success was obtained in 46 patients (97.8%). In 12 patients (25.5%), a permanent reduction of the GFR was observed using postoperative TC-DTPA perfusion scintigraphy. By 99m TC-DTPA perfusion scintigraphy, a permanent reduction of GFR was observed postoperatively in 12 patients. A slight GFR reduction (<20%) was present in 7 (14.9%) patients, due to the planned occlusion of accessory renal arteries. A more significant GFR reduction (>20%) was present unexpectedly in 5 (10.6%) patients, in 3 of these a single kidney was involved, in 5 both with an increase of the serum creatinine level >20%. Suprarenal fixation of endografts in AAA treatment is a safe procedure with good early and midterm procedural results and a risk of GFR impairment (>20%) of 10.6%.

Cold and heat pain assessment of the human oesophagus after experimental sensitisation with acid

The aim of the present study was to investigate the effect of thermal stimulation of the oesophagus before and after sensitisation with acid. In 17 healthy subjects a stimulation bag was used to re-circulate water at 5 and 60 °C for up to 90 s in the lower part of the oesophagus. The area under the temperature curve was used to assess the caloric load. The thermal stimuli were repeated after perfusion of the oesophagus with acid. The evoked pain intensity and referred pain areas (at the pain threshold) were assessed. At baseline the subjects were able to tolerate less caloric load (42%) for the heat compared to the cold stimuli ( P=0.007). The heat stimuli resulted in an increased referred pain area as compared with the cold stimuli ( P=0.03). Following acid perfusion there was a selective sensitisation to the heat pain stimuli as only 36% of the initial caloric load was tolerated ( P=0.012), whereas the sensation to the cold stimuli was unchanged. After acid perfusion, the referred pain area to the heat pain stimulation increased 49% ( P=0.04), but was not changed to cold stimulation ( P=0.82). After sensitisation the words used to describe the sensations to heat pain stimuli shifted from a warmth quality towards a more burning quality in most subjects. This multi-modal sensory testing study showed that acid sensitises the oesophagus to heat but not to cold pain. This may account for the modality-specific symptoms and hypersensitivity reported in patients suffering from, e.g. gastro-oesophageal reflux disease.

Lack of Association Between Esophageal Acid Sensitivity Detected by Prolonged pH Monitoring and Bernstein Testing

Heartburn, a common medical symptom, is thought to be the result of acid reflux into the esophagus. Perfusion of the esophagus with exogenous acid (Bernstein test) in susceptible individuals causes heartburn. Temporal correlation between heartburn and pH drop in the esophagus from endogenous acid, as reflected by a positive symptom index (SI), provides further evidence of a correlation between acid in the esophagus and heartburn. We tested the relationship between heartburn and acid in the esophagus by determining the SI and Bernstein test results in the same individual. Ninety-three patients with heartburn underwent 24-h pH monitoring and Bernstein testing. A Bernstein score that included the severity of heartburn and the time of heartburn onset during Bernstein test was calculated. The relationship between SI, Bernstein test, and Bernstein score was determined. Fifty-eight patients reported symptoms during the prolonged pH recording. A positive SI was detected in 27 patients. Forty-nine patients had a positive Bernstein test. There was no correlation between the patients with a positive SI and positive Bernstein test results. There was no correlation between SI and Bernstein score. A positive Bernstein test within 5 min of acid infusion did not predict heartburn during spontaneous reflux episodes of >/=5 min. The lack of association between symptoms induced by acid perfusion of the esophagus compared with symptoms following spontaneous reflux in the same individual suggests that the heartburn following acid perfusion and spontaneous heartburn are induced by different stimuli.

Low-dose PGE2 mimics the duodenal secretory response to luminal acid in mice.

Luminal exposure to concentrated acid, the most accepted physiological stimulus for duodenal bicarbonate secretion (DBS), cannot be used with in vitro preparations due to potential tissue damage. We thus examined whether exposure to PGE(2), a well-characterized physiological duodenal secretagogue, could mimic the effects of acid perfusion. DBS was measured in C57/BL mice by pH-stat/back-titration and measurement of total dissolved CO(2) concentration ([CO(2)](t)). Anion transport inhibitor DIDS, anion channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), carbonic anhydrase inhibitor methazolamide, and nonselective cyclooxygenase inhibitor indomethacin were used to inhibit separate components of HCO(3)(-) secretory pathway. Baseline DBS was not altered by exposure to methazolamide (0.1 mM) but was slightly reduced by DIDS (0.5 mM). DBS and [CO(2)](t) increased after acid and PGE(2) exposure. DIDS (0.5 mM) and NPPB (0.2 mM) abolished acid-induced DBS increase. Methazolamide (0.1 mM) and DIDS inhibited acid-induced [CO(2)](t) increase. DIDS, NPPB, or methazolamide had little effect on DBS in response to high concentration PGE(2) (100 microg/ml). Low concentration PGE(2) (1 microg/ml) increased DBS that was inhibited by DIDS, NPPB, and methazolamide. Pretreatment with indomethacin (5 mg/kg) inhibited DBS induced by acid exposure but not by PGE(2). High-dose PGE(2) substantially increases DBS by a mechanism that appears to be different than secretory response to luminal acid perfusion. Secretory response to low-dose PGE(2), at least in terms of inhibitor profile, closely resembles secretion in response to perfusion of physiological acid concentrations and may be a useful stimulus for in vitro study of DBS in isolated mouse duodenum.

Expression and localization of c-Fos and NOS in the central nerve system following esophageal acid stimulation in rats.

To determine the distribution of neurons expressing c-Fos and nitric oxide synthase (NOS) in the central nerve system (CNS) following esophageal acid exposure, and to investigate the relationship between c-Fos and NOS. Twelve Wistar rats were randomly divided into two equal groups. Hydrochloric acid with pepsin was perfused in the lower part of the esophagus for 60 min. As a control, normal saline was used. Thirty minutes after the perfusion, the rats were killed and brains were removed and processed for c-Fos immunohistochemistry and NADPH-d histochemistry. Blood pressure (BP), heart rate (HR), and respiratory rate (RR) during the experimental procedures were recorded every 10 min. There were no significant differences in BP, HR and RR between the two groups. c-Fos immunoreactivity was significantly increased in rats receiving acid plus pepsin perfusion in amygdala (AM), paraventricular nucleus (PVN), parabrachial nucleus (PBN), nucleus tractus solitarius and dorsal motor nucleus of vagus (NTS/DMV), nucleus ambiguous (NA), reticular nucleus of medulla (RNM) and area postrema (AP). NOS reactivity in this group was significantly increased in PVN, PBN, NTS/DMV, RNM and AP. c-Fos and NOS had significant correlation between PVN, PBN, NTS/DMV, RNM and AP. Acid plus pepsin perfusion of the esophagus results in neural activation in areas of CNS, and NO is likely one of the neurotransmitters in some of these areas.

Asthme et reflux gastro-œsophagien

Asthma and gastroesophageal reflux (GER) frequently coexist in patients. GER is usually considered to be potential trigger for asthma symptoms. This hypothesis is based more on pathophysiological considerations than on clinical data. Indeed, experimental data show that acid perfusion of the lower esophagus in humans induces increased bronchial hyperreactivity, and various mechanisms have been proposed to explain this observation. Recent studies also demonstrate that, in patients with asthma, obstruction induced by non-specific bronchial challenge increases the number of reflux episodes. This suggests that asthma by itself might be responsible for GER. Despite these facts, a review of published reports claiming to demonstrate the clinical effectiveness of medical or surgical treatment of GER on asthma symptoms yields inconsistent results. Nevertheless, it appears that a few asthmatic patients do benefit clinically and/or have improved lung function when treated for GER. However, the criteria for patient selection and, especially, the anti-reflux treatment modalities (choice and dose of medication and the duration of treatment) need to be more clearly defined through additional studies.

Effects of nitric oxide synthase inhibitor to esophagus in a feline esophagitis model.

The present study explores the effects of nitric oxide synthase inhibitor on esophageal motility in a feline model with esophagitis. Perfusion of the esophagus with acid produced inflammatory changes of esophageal mucosa. The esophageal motility was measured before and after the perfusion. One group of cats was given nitric oxide inhibitor orally at the same time as the perfusion of acid. The control group was given water instead. Esophagitis impairs the motility of the esophagus. However, the esophageal motility of the cats that were given nitric oxide synthase inhibitor decreased less than that of the control group. The results suggested that during esophagitis there is an alteration of the nitric oxide synthase/nitric oxide pathway in the esophagus, which may be one of the important mechanisms of esophageal motility dysfunction.

Diminished mechanosensitivity and chemosensitivity in patients with achalasia.

The pathogenesis of achalasia involves the degeneration of enteric and autonomic nervous systems with resultant effects on esophageal motility. The neural degeneration could affect visceral sensation in achalasia. The aim of this study was to examine mechanosensitivity and chemosensitivity in patients with achalasia. Perceptual responses to esophageal distension and acid perfusion were assessed in nine achalasia patients and nine healthy subjects. Mechanosensitivity was evaluated using a barostat with a double-random staircase distension protocol. Responses were graded as follows: 0, no sensation; 1, initial sensation; 2, mild discomfort; 3, moderate discomfort; and 4, pain. Chemosensitivity was graded along a visual analog scale after perfusion of saline and 0.1 N HCl. Barostat pressure-volume relationships were used to report esophageal body compliance. Barostat pressures for initial sensation and mild discomfort were not significantly different for patients and controls. The pressures for moderate discomfort (37.9 +/- 3.5 vs. 25.7 +/- 2.4 mmHg; P < 0.05) and pain (47.8 +/- 2.3 vs. 32.2 +/- 3.5 mmHg; P = 0.002) were significantly higher in achalasics than controls. Seven of the eight achalasia patients never reached pain thresholds at the maximum distension pressure (50 mmHg). Sensation to acid perfusion was significantly lower in achalasics compared with controls (2.2 +/- 1.2 vs. 6.7 +/- 1.7 cm; P < 0.05). Compliance was significantly increased in patients with achalasia compared with controls. We conclude that both mechanosensitivity and chemosensitivity are significantly diminished in achalasia patients compared with controls. Also, initial sensation and pain sensation are differentially affected in achalasics. These findings suggest that neuropathic defects in achalasia may manifest themselves in visceral sensory and motor dysfunction.

Microtubule-associated protein 2 (MAP2) expression during synaptic plasticity in the guinea pig cochlea

The expression of different isoforms of microtubule-associated proteins 2 (MAP2), including the low molecular weight form MAP2c present mainly in developing neurons, was investigated in the primary auditory neurons after α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) perfusion in the guinea pig cochlea. MAP2 expression appeared to be tightly regulated in the repairing neurons. Neurite regrowth seems to involve the MAP2c isoform. In cochlear neurons, mechanisms involved in the period of development might be reactivated after excitotoxic injury in the mature cochlea.

Characterization of the cerebral cortical representation of heartburn in GERD patients.

Although symptoms arising from the esophagus such as heartburn and pain can at times become challenging clinical problems, esophageal viscerosensation, especially with regard to chemical stimulation in humans, is incompletely understood. Our aims were 1) to characterize and ascertain the reproducibility of cerebral cortical registration of heartburn and 2) to elucidate the differences between these findings and those of esophageal subliminal acid stimulation in asymptomatic controls. We studied 11 gastroesophageal reflux disease (GERD) patients (9 males, 30-55 yr) and 15 healthy controls (8 males, 21-49 yr). Cerebral cortical functional magnetic resonance imaging (fMRI) activity was recorded twice in each subject, during two 5-min intervals of 0.1 N HCl, separated by 5 min of NaCl perfusion. Time from onset of acid perfusion to instant of fMRI signal increase and first report of heartburn averaged 1.60 +/- 0.80 and 1.85 +/- 0.60 min, respectively. Average maximum percent signal increase in the GERD patients (16.3 +/- 3.5%) was significantly greater than that of healthy controls (3.8 +/- 0.9%; P < 0.01). Temporal fMRI signal characteristics during heartburn were significantly different from those of subliminal acid stimulation in controls (P < 0.01). Activated cortical regions included sensory/motor, parieto-occipital, cingulate and prefrontal regions, and the insula. There was 92% concordance between the activated Brodmann areas in repeated studies of GERD patients. Cortical activity associated with perceived and unperceived esophageal acid exposure in GERD patients and healthy controls, respectively, involves multiple brain regions but occurs more rapidly and with greater intensity in GERD patients than the activity in response to subliminal acid exposure in healthy controls. The cortical pain-processing pathway seems to be involved in perception of esophageal acid exposure and could explain the variations encountered in clinical practice defining this sensation.

Effect of intraesophageal perfusion of chenodeoxycholic acid in patients with non-erosive gastroesophageal reflux

Effect of intraesophageal perfusion of chenodeoxycholic acid in patients with non-erosive gastroesophageal reflux

Esophageal acid perfusion in conditioned athletes while running decreases performance in subjects without a history of heartburn, but not in runners with heartburn history

Purpose: We have recently demonstrated increased acid reflux into the esophagus of conditioned athletes during exercise. Extraintestinal manifestations of GERD include asthma and laryngitis suggesting acid reflux into the esophagus may alter athletic performance. The aims of this study were 1) to compare 'exercise to exhaustion' in conditioned athletes with and without a history or heartburn while the esophagus is perfused with saline (sham) or 0.1 N HCl (Bernstein) and 2) to assess the effect of acid perfusion on pulmonary function after exercise.