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For hypertensive lower esophageal sphincter with dysphagia and chest pain, a laparoscopic cardiomyotomy is recommended. Recently, the role of gastroesophageal reflux in this abnormality has been recognized. A prospective study on six patients with manometrically proven hypertensive lower esophageal sphincter was performed. Laparoscopic floppy Nissen fundoplication was performed in all cases. The first follow up was performed 6 weeks after the operation. The mean follow up time was 56 months (range 50-61). Before the operation, all patients had abnormal esophageal acid exposure. Mean DeMeester score was 41.7 (range 16.7-86). Average LES pressure before the operation was 50.5 mmHg (range 35.6-81.3). Six weeks after operation, all patients were symptom free. DeMeester score returned to a normal level of 2.9. Furthermore, a marked decrease in the lower esophageal sphincter pressure (24.7 mmHg) was detected. At late follow up, all patients were symptom-free, and only two patients agreed to undergo functional testing. The mean DeMeester score of this two patients was 1.2. The pressure remained at normal value (15.7 mmHg). In our study, an antireflux operation normalized lower esophageal sphincter pressure suggesting that abnormal esophageal acid exposure may be an etiologic factor in the development of hypertensive lower esophageal sphincter.

Two achalasia patients with former complaints of heartburn were examined. Antisecretory drugs were used by the patients when dysphagia occurred. Barium X-ray and esophageal manometry were performed and achalasia was diagnosed in both patients. Twenty-four-hour pH-metry showed significant and long-lasting acid reflux during supine position. Prolonged reflux episodes can be explained not only by the swallow-unrelated transient relaxation of lower esophageal sphincter (LES) and mechanical damage of the esophageal body, but also by its chemical insensitivity. Thus preoperative detection of reflux should determinate either the operational procedure and the postoperative follow up of the patient.

The physiologic importance of afferent sensory pathways in the esophageal motor functions has been recently recognised. Capsaicin-sensitive sensory afferents were shown to play a role in the maintenance of mucosal integrity of the GI tract, and regulation of human esophageal motility. The aim of this study was to investigate the effect of topical application of capsaicin-containing red pepper sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human esophagus of healthy volunteers and patients with Barrett’s esophagus. Methods : The diagnosis of Barrett’s esophagus was based on the findings of esophagoscopy and histology taken from the squamocolumnar junction of the esophagus. Esophageal motility was measured by perfusion manometry before and after application of red pepper sauce. Results : Capsaicin containing red pepper sauce increases the motility response (LES tone, contraction amplitude, propagation velocity) of the human esophagus in healthy volunteers. This response failed in patients with Barrett’s esophagus. Conclusion : Impaired esophageal sensorymotor function may serve as one etiologic role in the development of Barrett’s esophagus.

Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were investigated, as well as the underlying mechanisms of the responses. Gastric acid secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance technique), and mucosal vascular resistance (GMVR) and mean arterial pressure (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng) administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/- 5.3 to 100.6 +/- 20.9 ml.min-1.100 g-1 and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9 mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml-1.min.100 g, whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mumol/30 min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368 were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or decrease GMVR but did stimulate GAS. These data show that vagal stimulation by the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin-sensitive afferent fibers, whereas acid secretion is under the inhibitory influence of prostaglandins and CGRP.

Karadi O, Bodis B, Kiraly A, Abdel-Salam OME, Sutō G, Vincze A, Mozsik Gy. Surgical vagotomy enhances the indomethacin-induced gastrointestinal mucosal damage in rats. Inflammopharmacology. 1994;2:389-399.

Mechanisms mediating the increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a gastric acid secretory dose (30 ng) were investigated using hydrogen gas clearance in urethan-anesthetized rats. The histamine H1 receptor antagonist pyrilamine (intravenously), capsaicin (subcutaneously, −10 days), and N G-nitro-l-arginine methyl ester (l-NAME, intracisternally) failed to impair the 150% rise in GMBF induced by intracisternal injection of RX-77368. By contrast, atropine (subcutaneously) and N G-monomethyl-l-arginine (intravenously) completely inhibited the increase in GMBF evoked by intracisternal RX-77368. l-NAME (intravenously) blocked the intracisternal RX-77368-induced increase in GMBF in capsaicin-pretreated rats, and thel-NAME effect was reversed by intravenous l- but notd-arginine. These findings indicate that vagal efferent activation induced by TRH analog injected intracisternally at a gastric acid secretory dose increases GMBF through atropine-sensitive mechanisms stimulatingl-arginine-nitric oxide pathways, whereas H1 receptors and capsaicin-sensitive afferent fibers do not play a role.

Peptic ulceration including acute erosions is a multifactorial disease involving well-known factors such as trauma, stress, sepsis, hemorrhagic shock, burns, pulmonary and liver diseases1–9 and drugs such as reserpine10, epinephrine11–13, nonsteroidal antiinflammatory drugs7, steroids and other chemicals14.

Background/Aims: Interleukin 1β (IL-1β) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1β on gastric emptying were investigated. Methods: The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1β in conscious rats. Results: IL-1β injected intracisternally (0.01–1 ng) or intravenously (0.01–10 ng) dose-dependently decreased gastric emptying by 10%–82% and 0%–89%, respectively. The median effective dose (ED 50 ) was 30-fold lower when IL-1β was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1β had a rapid onset (within 20 minutes) and was long-lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1β (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe 12 , Nle 21,38 ,C α MeLeu 37 ]CRF 12–41 (20 μg) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1β (0.1 ng). The antagonists alone had no effect on basal gastric emptying. Conclusions: IL-1β acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1β action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.

Gastric cytoprotection in response to different agents (prostaglandins, carotenoids, etc.) failed to occur after surgical vagotomy. Decreased gastric emptying and the increased vascular permeability were tested in ethanol-treated rats without and with bilateral surgical vagotomy. The experiments were carried out on Sprague-Dawley rats. The animals were fasted for 24 h before experiments. Bilateral surgical vagotomy or only laparatomy were carried out at 30 min before administration of ethanol (96%, 1 ml). The animals were killed at 0, 1, 5, 15, and 60 min after ethanol administration, when the number and severity of gastric mucosal lesions were noted. In another series of experiments, the animal received Evans blue (1 mg/100 g) i.v. 15 min before killing. The gastric contents were collected and the glandular mucosa was scraped. Evans blue was extracted in chloroform, and its concentration was spectrophotometrically measured. It has been found that (a) both number of lesions and severity of ethanol-induced gastric mucosal damage were larger at each time period in surgically vagotomized rats than in rats with intact vagal nerves; (b) the increased vascular permeability was significantly higher in gastric mucosa at an early period in surgically vagotomized rats compared to rats with intact vagal nerve; (c) the increased vascular events preceded the development of macroscopic appearance of gastric mucosa damage in both groups of animals; and (d) the time-related responses were the same in both groups of animals. It is concluded that increased vascular permeability, but not gastric emptying, probably has some role in the failure of the development of gastric cytoprotection in surgically vagotomized rats.