Relationship Between Esophagheal Motility And Viscera Sensitivity Function In GERD

Part ⅠControl of transient lower esophageal sphincter relaxations and reflux by the GABA_B agonist baclofen in normal subjectsObjective: To observe the effect of a GABA_B agonist baclofen on postprandial gastroesophageal reflux and transient lower esophageal sphincter relaxations (TLESR), in order to investigate therapeutic agents of baclofen for the management of relux in patients with gastroesophageal reflux disease in Chinese.Methods: Using placebo cross-over control design to study the effect of baclofen on pH, transient lower esophageal sphincter relaxations and lower esophageal sphincter pressure. In 16 healthy volunteers, esophageal motility and pH were measures, with the subjects in the sitting position, for 4 hours (1 hour before the meal and 3 hours after the meal). On separate days at least 1 week apart, 40mg oral baclofen or placebo was given 110 minutes before the meal.Results: The data of the rate of TLESR, rate of reflux episodes, proportion of TLESR associated with reflux are presented as median (interquartile range) and the data of LES pressure are presented as mean (SD). (1) Baclofen significantly reduced the postprandial rate of acid reflux episodes. ① 278 episodes of acid reflux were detected totally. Baclofen significantly reduced the rate of acid reflux episodes changed from 3 (1-3.25)/3h to 1(0-2)/3h (P=0.006). ② Baclofen significantly reduced the rate of acid reflux episodes changed from 3(3-4)/h to 1 (1-2)/h during the first postprandial hour (P=0.026). This effect was not significant for the second and third postprandial hours.③ In placebo group there is no difference in the rate of acid reflux episodes during the postprandial hours each (P>0.05). (2) Baclofen significantly reduced the postprandial rate of TLESR. ①Baclofen significantly reduced the rate of TLESR changed from 4.5 (3-6)/3h to 1.5 (1-2)/3h (P=0.0004). ② Baclofen significantly reduced the rate of TLESR changed from 7.5 (6-8)/h to 3.5 (1-5)/h during the first postprandial hour. This effect was significant for the second and third postprandial hours.③ In placebo group the rate of TLESR in the second and third postprandial hours was significant decreased than the first postprandial hour. ④Baclofen had no effect on the proportion of TLESR associated with reflux (29% vs 27%, P=0.67). (3)Baclofen significantly increased basal lower esophageal sphincter pressure (8.72±1.27mmHg vs11.36±2.73mmHg, P=0.03). (4)On both study days, the majority of reflux episodes occurred during TLESR and swallow induced LES relaxation. Baclofen had no effect of the mechanisms of reflux. And Baclofen had no effect of esophageal peristalsis.Conclusions: In normal human subjects, the GABA_b agonist baclofen significantly inhibits gastroesophageal reflux by inhibition of transient LES relaxations. This finding suggest that GABA_b agonist may be useful as the management of reflux in patients with gastroesophageal reflux disease in Chinese. PartⅡThe viscera sensitivity in patients with gastroesophageal reflux diseaseObjective: To study the chemosensitivity and mechanosensitivity in patients with gastroesophageal reflux disease, in order to investigate the effect of viscera sensitivity in gastroesophageal reflux disease.Methods: 16 health volunteers, 15 NERD and 17 RE were enrolled in the study. Mechanosensitivity was evaluated with a barostat. Chemosensitivity to acid was determined by intraluminal acid perfusion.Results: Positive perfusion test were found in 67% NERD and 59% RE, significantly higher than health volunteers. Among the positive perfusion test's patients, acid perfusion sensory score (APSS) in NERD were much higher than that of RE, which difference appears significantly (P=0.03). Using stepwise distention the perception and pain threshold were significantly decreased in NERD than controls. But there was only significant difference in perception threshold between RE and healthy controls. The pain threshold was significantly lower in NERD than RE (P = 0.03). There is no difference in esophageal body compliance between three groups. The perception and pain threshold were significant lower in positive acid test's patients than the others. APSS was correlated with the pain threshold. There was no difference between different distention protocols.Conclusions: The viscera sensitivity is different between NERD and RE. NERD is enhanced sensitivity to acid and esophageal balloon distention. But RE is only enhanced sensitivity to acid. Intraesophageal balloon distention using stepwise protocols is a reproducible method of measuring esophageal sensory thresholds. PartⅢCorrelation between acid reflux and esophageal dysmotility in patients with gastroesophageal reflux diseaseAims: To investigate the correlation between esophageal motility and acid reflux, and their relations to esophageal mucosal injury in patients with GERD.Methods: A total of 72 patients with typical reflux symptoms as regurgitation,heartburn, and chest pain were recruited and evaluated by upper gastrointestinal endoscopy, esophageal manometry and 24-h pH monitoring. Patients with endoscopic esophagitis were divided into physiologic reflux (pH~-) and pathologic reflux (pH~+) groups in accordance with the criteria of the total percentage time of pH below 4 <4.5% and DeMeester score <14.7.Results: More patients with endoscopic esophagitis had pathologic reflux than patients without esophagitis. Results of parameters of 24-h pH monitoring were significantly higher in esophagitis group than those in non-esophagitis group (P<0.05). However,there was no statistically significant difference in esophageal manometry readings between patients with and without esophagitis. In esophagitis group, lower esophageal sphincter pressure (LESP), speed of esophageal peristalsis transmission, and the success rate of wet swallowing were significant lower in patients with pathologic reflux than those in patients with physiologic reflux (P<0.05).Conclusions: The development of esophagitis in GERD has a close relation with acid reflux and patients with pathologic reflux are more likely having esophageal dysmotility.