Cisapride inhibits meal‐stimulated gastric acid secretion and post‐prandial gastric acidity in subjects with gastro‐oesophageal reflux disease

Abstract

Summary Background and aims : KCNQ1 potassium channels in human gastric parietal cells are thought to be involved in gastric acid secretion. As cisapride can inhibit similar channels in other tissues and is an effective treatment for nocturnal heartburn, we examined the effects of cisapride on gastric and oesophageal acidity, gastric emptying and heartburn severity in subjects with gastro‐oesophageal reflux disease. Methods : Subjects (n=11) had suffered from heartburn four times or more per week for at least 6 months. Gastric pH and oesophageal pH were measured before, during and after a standard meal ingested over 15 min. Each subject received placebo or 10 mg cisapride orally, 30 min before the beginning of the meal. Meal‐stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Heartburn severity was assessed at 15‐min intervals beginning at the end of the meal. Gastric emptying of solids was measured using a [13C]‐octanoic acid breath test. Results : Cisapride significantly decreased meal‐stimulated gastric acid secretion by 20%, decreased integrated gastric and oesophageal acidity by 50–60% and transiently increased the expiration of 13CO2. Cisapride did not significantly alter heartburn severity. Conclusions : The cisapride‐induced decreases in meal‐stimulated gastric acid secretion, gastric acidity and oesophageal acidity in subjects with gastro‐oesophageal reflux disease can account for its beneficial clinical effects. These results also raise the possibility that gastric KCNQ1 potassium channels are important in meal‐stimulated gastric acid secretion and possibly in the pathophysiology of gastro‐oesophageal reflux disease.

Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease

“…However, treatment with prokinetic agents has been shown to improve several symptoms in patients with GERD (16,39), and we have recently demonstrated that cisapride improves the motility proximal to the lower esophageal sphincter in GERD rats (40). These findings suggest that gastrointestinal dysmotility is involved in GERD progression.…”

“…Delayed gastric emptying occurs frequently among patients with acid reflux (3,31), and treatment with prokinetic agents, which are agonists of the 5-hydroxytryptamine 4 (5-HT 4 ) receptor, partially improves symptoms in patients with GERD (16,39). Thus it was concluded that gastric dysmotility is also a factor involved in acid reflux into the esophagus (3,10,29,31).…”

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

“…Published evidence suggests that oral cisapride does not modify postprandial LOS motor function [25,26], although an overnight study showed a decrease in the rate of transient LOS relaxations [27]. It cannot be excluded therefore that cisapride decreased the number of acid (pH B/4) reflux episodes only, instead of the total number of reflux episodes through its decreasing effect on mealstimulated gastric acid secretion [28], a hypothesis that needs to be tested by combined intra-oesophageal pH and impedance monitoring.…”

Meal‐stimulated gastric acid secretion and integrated gastric acidity in gastro‐oesophageal reflux disease

“…Subsequently, we developed a technique to measure meal‐stimulated gastric acid secretion based on the buffer capacity of the meal determined in vitro and the time required for the gastric pH to decrease to pH 2 in vivo following ingestion of the meal 16 ,. 17 These studies, however, involved a single meal ingested by subjects who were restricted to a bed or a chair in a study unit 16 ,. 17 …”

“… 17 These studies, however, involved a single meal ingested by subjects who were restricted to a bed or a chair in a study unit 16 ,. 17 …”