An in vitro study was performed to determine the in vitro sensitivity of rat esophagi to contracting and relaxing agonists in different alkaline mediums.

Twenty-four Wistar rats weighing 200 to 250 g were included in the study. After inducing anesthesia with thiopental sodium (50 mg/kg), the rats were killed, and the distal esophagus (DE) and gastroesophageal junction (GEJ) were removed. Excised tissues were suspended under 0.6 g of resting tension in a tissue bath containing 10 mL of Tyrode solution at 37°C. The esophageal segments were divided into 4 groups, each with a different pH medium: 7.4, 7.6, 7.8, and 8. To evaluate the smooth muscle activity of the rat esophagus in different alkaline mediums, cholinergic agonist carbachol (a cholinergic agonosit) and KCl (which acts on calcium channels) were added to the organ baths to obtain concentration-dependent contraction responses. Relaxation responses were obtained using an adrenergic agonist, isoproterenole. Data obtained from different pH mediums were analyzed using Kruskal-Wallis nonparametric analysis of variance and post hoc Dunn's test.

The pH of the medium has no effect on the concentration-dependent contracting responses to carbachol in the DE, but responses obtained in pH 8 medium were significantly lower in the GEJ (P < .05). In pH 8 medium, concentration-dependent relaxation responses to isoproterenole were also significantly lower (P < .05). When contractile responses to KCl were evaluated, the groups with pH 7.6 and 7.8 medium were found to have higher responses in the DE segments than other groups (P < .05). However, the GEJ segments had lower contractile responses to KCl in pH 8 medium (P < .05).

Although different alkaline mediums caused no alteration in esophageal smooth muscle responses to cholinergic stimulation, GEJ responses were lower in pH 8 medium. Relaxation responses, owing to increased adrenergic activity, decreased when the pH of the medium was increased to 8. Calcium-dependent contractions caused by KCl decreased in both segments in pH 8 medium but increased in the DE in pH 7.6 medium.

The aim of this study is to determine the in vitro sensitivity of mouse esophagus to contracting and relaxing agonists in different pH medium values.

Forty-eight Swiss albino mice (30-40 g) of both sexes were anesthetized with tiopental sodium (30 mg/kg). After exsanguinations from abdominal artery, esophagi were removed and suspended under 0.6 g of resting tension in a tissue bath containing 10 mL of Krebs solution at 37 degrees C. The experiments were performed in different pH mediums 7.4, 6.4, 4, and 2. Carbachol and acetylcholine were used as contractile agonists, and noradrenalin and isoproterenol to evaluate relaxation responses. Data concerning similar concentrations of contractile agonists obtained from different pH mediums were analyzed using Kruskal-Wallis nonparametric analysis of variance and post hoc Dunn test. Relaxation responses were compared with Student t test. A P value less than .05 was considered significant. The study was approved by Local Ethical Committee of Kirikkale University.

Carbachol and acetylcholine caused concentration-dependent contractility in pH 7.4, 6.4, and 4, but contractile responses were inhibited in pH 2. In carbachol and acetylcholine experiments, there was a significant decrease in contractile responses to all concentrations in conjunction with a decreased in pH value. Relaxation responses in pH 2 and 4 could not be obtained because precontraction of tissues was not possible. Noradrenalin and isoproterenol produced concentration-dependent relaxations in pH 7.4 and 6.4. Although noradrenalin responses showed no significant difference according to pH, isoproterenol caused better relaxations in pH 6.4 (between 10(-8) and 10(-6) mol/L) when compared to pH 7.4 studies.

The mouse esophagus has impaired contractile responses to carbachol and acetylcholine in decreased pH values. Contraction responses did not occur in pH medium of 2. In contrast, esophagus segments showed better relaxations in lower pH values with isoproterenol.

Esophagitis is associated with an impaired esophageal peristalsis. A few studies have been aimed at understanding the pathophysiology of abnormal peristaltic activity. The mechanism of impaired esophageal smooth muscle reactivity in the chronic gastroesophageal reflux (GER) model is investigated in vitro for the first time.

The chronic GER rat model was created by partial gastric outlet obstruction. The histopathological findings related to esophagitis were evaluated. Smooth muscle strips of the tunica muscularis mucosa of esophagus were studied in standard organ chambers. Carbachol- and KCl-induced contractile responses and serotonin- and papaverine- induced relaxant responses in both reflux and sham-operated control groups were determined.

Histopathologically, chronic reflux esophagitis was observed in all specimens of the reflux group. Contractile (carbachol- and KCl-induced) smooth muscle responses were significantly decreased in the reflux group. When compared to control group, relaxant response of smooth muscle to serotonin was also significantly decreased in the reflux group. However, there was no difference in papaverine-induced relaxant responses between 2 groups.

Our study describes the effects of chronic GER on rat esophageal smooth muscle contractility in vitro. We found that both receptor- (carbachol, serotonin) and nonreceptor-mediated (KCl) esophageal smooth muscle reactivity were impaired in chronic reflux esophagitis. These changes may correspond to the functional motor abnormalities of the esophagus seen in patients with chronic reflux esophagitis.

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.

In GERD patients, ineffective esophageal motility (IEM), a hypocontractile disorder, is the most common motor abnormality. IEM has been associated with reflux in both the supine and upright position, prolonged esophageal clearance, and delayed of bolus transport. IEM has been equally present in erosive and in nonerosive GERD.

Considering that reflux has been found to be more severe in erosive GERD than in nonerosive GERD patients and that IEM delays esophageal clearance, our hypothesis is that patients with erosive GERD have more severe IEM than those with nonerosive disease.

A retrospective review of consecutive manometries of patients with the chief complaint of heartburn and a diagnosis of IEM were performed, and patients with both erosive and nonerosive GERD were selected. According to the number of ineffective contractions, IEM was stratified into three groups: 30% to 40%, mild; 50% to 60%, moderate; and greater than 60%, severe. We also registered the number of low amplitude, failed, and normal waves in each manometry of both groups. We evaluated 110 patients: 70 (64%) with erosive GERD and 40 (36%) with nonerosive GERD. The percentage of mild, moderate and severe IEM was similar in erosive and in nonerosive GERD patients, as well the number of low amplitude, failed or normal waves (P < 0.5).

There were no differences between the severity of IEM in erosive and in nonerosive GERD patients.

Motility abnormalities, common in gastroesophageal reflux disease, are likely to be related to endoscopic esophagitis. We studied pH and manometry parameters in relation to the severity of esophagitis. Forty-seven patients with symptomatic gastroesophageal reflux disease for > 3 months were evaluated by: (i) endoscopy (grading of esophagitis by Savary-Miller classification); (ii) mucosal biopsy; (iii) manometry; and (iv) 24-h pH-metry. We found Savary-Miller's grades of: 0 (9 patients out of 47), I (16/47), II (16/47), III (4/47), IV (2/47). Distal esophageal contraction amplitude was lower in severe (grade II to IV) as compared with mild (grade 0 and I) esophagitis (49 [7-182] versus 83 [27-196] mmHg [P = 0.001]). The length and pressure in the lower esophageal sphincter (LES), duration and velocity of contraction in the body, number of episodes of reflux and long-duration reflux, longest reflux, median pH, per cent of time with pH < 4 and DeMeester scores were not significantly different between the two groups. The area under pH 4 showed a negative correlation with LES pressure and amplitude of distal esophageal contractions. We conclude that higher endoscopic grades of esophagitis are associated with lower amplitude of contraction in distal esophagus. Lower LES pressure and distal esophageal contraction amplitude are associated with greater area under curve for pH below 4.

The present study investigated how reflux-induced esophagitis affects the smooth muscle reactivity of the esophageal body. Two different esophagitis models were used: acid gastric and mixed duodenogastric reflux. All test animals apart from the controls developed gross and histologic evidence of esophagitis. Contractile (carbachol and KCI) and relaxant (isoproterenol) esophageal smooth muscle responses were significantly decreased in the presence of acid- and mixed reflux-induced esophagitis. Similar relaxant responses to serotonin and papaverine were found in the three groups. Our study demonstrated impaired esophageal smooth muscle reactivity when esophagitis was induced by acid or mixed reflux. These changes may correspond to the functional motor abnormalities of the esophagus seen in patients with reflux esophagitis.

To study the esophageal motility of patients with esophageal adenocarcinoma or Barrett esophagus with high-grade dysplasia before and after photodynamic therapy.

In this prospective study conducted between January 1998 and October 1999, esophageal motility testing of the lower esophageal sphincter and esophageal body was performed with a water-perfused catheter, 2 days before and at least 3 weeks after patients underwent photodynamic therapy for esophageal adenocarcinoma or Barrett esophagus. Results were classified as normal motility, ineffective esophageal motility, or aperistalsis.

Twenty-three patients were studied, 13 with carcinoma and 10 with Barrett esophagus. Overall, 11 patients (48%) had normal motility, 6 (26%) had ineffective esophageal motility, and 6 (26%) had aperistalsis. Five patients with aperistalsis had carcinoma. Follow-up tracings after photodynamic therapy found that 6 patients (26%) had normal motility, 7 (30%) had ineffective esophageal motility, and 10 (43%) had aperistalsis.

Esophageal dysmotility is common in patients with esophageal adenocarcinoma or Barrett esophagus. Photodynamic therapy may worsen esophageal motility in some patients. Dysphagia after photodynamic therapy therefore may be related to underlying esophageal dysmotility and may not always be caused by stricture or underlying carcinoma.

Patients who present with uncontrolled esophageal acid reflux symptoms require endoscopy to determine the presence or absence of ulcers and stenoses, acid reflux testing to determine if acid reflux is present, and manometry to evaluate esophageal peristalsis and spastic states. These studies are usually done in stages, at separate times. Esophageal manometry catheters currently in use have an incorporated infusion channel. This allows instillation of a dilute acid meal after esophageal manometry has been completed. Standard acid reflux testing can then be done using dynamic positioning and physiologic maneuvers. When combined with an esophagogastroduodenas copy (EGD), these three studies provide all information necessary within 2-3 h to determine further treatment of these patients. A total of 210 patients underwent these studies. A hiatus hernia was present in 84%. An ineffective lower esophageal sphincter was found in 64%. Esophageal hypocontractility was present in 18%, hypercontractility in 14%, and dysmotility in 36%. Upper esophageal sphincter was weak in 42%, hypercontractile in 42%, and dysmotile in 32%. Acid reflux disease was found in the hiatus hernia in 14% and acid reflux to the level of the lower esophagus in 16%, middle esophagus in 13%, and upper esophagus in 40%. Distal esophagitis was present in 47%, esophageal ulceration in 29%, gastric prolapse in 11%, gastritis in 52%, bile reflux disease in 10%, and Barrett's epithelium in 5%. In conclusion, an extremely high number of patients with esophageal acid reflux disease show dysmotility patterns. Standard acid reflux testing using dynamic positioning will identify most patients with significant acid reflux disease. When combined with an EGD, complete testing for acid reflux disease can be performed at one setting. Further study is needed comparing dynamic acid reflux testing to 24-h pH testing.

Esophageal dysmotility occurs in association with GERD; however, the cause of these motility abnormalities is not known. It is also not clear whether injury results from the presence of acid itself, inflammatory change or fibrosisin the esophageal wall. It is also unclear if reversal of these abnormalities takes place, and if so, to what degree. There are, however, a subset of patients who seem to have improvement with effective medical or surgical therapy, parodoxically, the same patients in whom a fundoplication, particularly a complete wrap, would lead to severe postoperative dysphagia secondary to preoperative dysmotility. What does all this mean for the individual patient? It is likely that most will not have any important change in esophageal motility abnormalities with standard medical or surgical therapy. Fundoplication might be safely performed in patients with minimal motility abnormalities, but those with severe abnormalities should be approached with caution. The conservative approach is to perform a partial fundoplication (Toupet) in those with ineffective motility (> 30% low-amplitude or nontransmitted contractions). It is hoped that future investigations will aid in understanding the pathogenesis of these abnormalities and how they can be used more precisely to guide antireflux therapy.

Suppression of gastric acid secretion is widely used and logical for the treatment of acid-related diseases. Healing of duodenal ulcer, gastric ulcer and gastroesophageal reflux disease is correlated significantly with the degree and the duration of suppression of intragastric acidity over 24 hours and with the length of the treatment. To date, proton pump inhibitors are the most effective agents among the currently available antisecretory drugs in offering the highest healing rate and fastest resolution of symptoms. Combinations of an antisecretory drug with one or more antimicrobial agents accelerate healing of peptic ulcers.

Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day) were evaluated in a double-blind, randomized multicenter study in 474 symptomatic patients with erosive ulcerative reflux esophagitis. A total of 238 patients were treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinner-time. Relief of symptoms was significant in all patients after six and 12 weeks and not different in both treatment groups. Overall endoscopic healing was significantly better in the famotidine 40 mg twice a day group compared with 20 mg twice a day at week 6 (58% versus 43%; P < 0.05) and at week 12 (76% versus 67%; P < 0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a day in those patients not healed after 12 weeks did not result in further symptom relief or in significantly better overall healing. The differences in efficacy of these two doses were more pronounced with increasing severity of esophagitis. Analyzed by grade of esophagitis at entrance, healing was significantly better with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades III and IV, and at week 24 for grade IV esophagitis. The results show that in the treatment of erosive/ulcerative reflux patients famotidine 40 mg twice a day is more effective and achieves faster healing than famotidine 20 mg twice a day.

Much has been learned about the pathophysiology of gastro-esophageal reflux (GER) since it was initially described by Asher Winkelstein in 1935. With the development and refinement of esophageal function tests in the past decades, the diagnostic modalities have become available for a deliberate and systematic evaluation of antireflux mechanisms. Some of the newer concepts of the pathogenesis of reflux esophagitis are reviewed in this article.

Duodenal and gastric contents do reflux into the oesophagus and acid alone certainly causes oesophageal damage which will be worsened by pepsin. In the patient who has undergone gastrectomy duodenal secretions may also be harmful. There is evidence that when the two mix there may be a toxic synergism, leading to mucosal disruption and intracellular damage to oesophageal cells which produces the clinical picture of reflux oesophagitis, with or without symptoms. Clear evidence of the toxicity of duodenal refluxate in humans is lacking, but the ability to measure bile and acid reflux continuously, together with a method of detecting oesophageal damage at a cellular level should help to solve this long debated problem.