Does Rabeprazole Enhance Distension-Induced Gastric Accommodation?

Abstract

To the EditorPostprandial relaxation of the proximal stomach, namely gastric accommodation, is a key mechanism for understanding symptom generation in functional dyspepsia [1]. Impaired gastric accommodation raises the postprandial intragastric pressure, thereby generating dyspeptic symptoms such as early satiety [1]. On the other hand, proton pump inhibitors (PPIs) are effective for relieving dyspeptic symptoms [1]. A human study has shown that rabeprazole, one of the newer drugs in the PPI class, increases production of nitric oxide, which mediates the relaxant response of the proximal stomach to a meal [2]. These observations suggest the possibility that PPIs enhance gastric accommodation. However, the possibility has not yet been addressed.Gastric accommodation is induced by duodenal exposure to nutrients or by gastric distension [3]. The nutrientinduced accommodation is studied using the gastric barostat by monitoring the incremental change in barostat volume after a caloric liquid meal, while keeping intragastric pressure constant. However, by this conventional barostat technique, the distension (pressure)-induced accommodation cannot be evaluated [4]. A recent study has shown that rapid gastric emptying (GE) of 1,000 ml of water can be a surrogate marker of impaired distensioninduced accommodation [5]: after aggressive gastric filling with 1,000 ml water, the resultant elevation in intragastric pressure determines GE, and therefore the higher luminal pressure due to the defective accommodation, accelerates GE [5]. In reverse, it is logical to consider that GE of 1,000 ml water is delayed when the distension-induced accommodation is enhanced. The aim of this preliminary study was to test our hypothesis that rabeprazole delays GE of 1,000 ml water. If the hypothesis is true, the enhancing effect of rabeprazole on distension-induced gastric accommodation will indirectly be supported.Nine, healthy, Helicobacter pylori-seronegative, male volunteers (30-39 years, 55-85 kg) were enrolled. All gave written informed consents and the study was approved by the Ethics Committee of Teikyo University. The [ 13 C]-acetate breath test was performed on two randomized occasions [6,7], which were at least 1 week apart. On one occasion, 20 mg of rabeprazole was orally administered for the preceding 2 days, and 1 h before the breath test on the third day. The last dose of rabeprazole was taken with 200 ml water. On the other occasion, the subjects received no pretreatment, but they drank 200 ml water 1 h before the test. On breath testing, 1,000 ml of mineral water containing 200 mg [ 13 C]-acetate was given at a rate of 200 ml/ min. Breath samples were collected at baseline and at 5-min intervals for 2 h. The half [ 13 CO 2 ] excretion time (t 1/2b ) and the time of the maximal [ 13 CO 2 ] (t lag ) were calculated [7]. Time course data of the [ 13 CO 2 ] excretion were analyzed using two-way repeated measures of analysis of variance, followed by a post hoc paired Student's t-test. Summary data (t 1/2b and t lag ) were analyze...

Effects of Proton Pump Inhibitors on Gastric Emptying: A Systematic Review

“…This method would not accurately reflect gastric emptying because absorption processes of a paracetamol tablet involve not only gastric emptying but also tablet dissolution [36]. The remaining three studies appear to be relevant for the pure effect of PPIs [14][15][16]. From the results of the only three studies, however, we cannot refer to any definitive conclusion at all.…”

“…The sample size was small (n \ 10) in eight of the 25 studies: three of the eight studies were about gastric emptying of inert liquids [11,14,16], three were about that of caloric liquids [17][18][19], and two about that of solids [24,25]. The three studies with inert liquids yielded statistically significant results.…”

“…This observation leads to a hypothesis that removal of acid by PPIs would restore or even enhance the gastric accommodation. In their preliminary report, Sanaka et al [14] addressed an enhancing effect of PPIs on the accommodation. They demonstrated that rabeprazole delayed gastric emptying of a large volume (1,000 ml) of water.…”

TRPV2 ion channels expressed in inhibitory motor neurons of gastric myenteric plexus contribute to gastric adaptive relaxation and gastric emptying in mice

“…Intragastric pressure was determined with an isolated mouse stomach. While it has been suggested that delayed gastric emptying (GE) was related to symptoms, recent studies have indicated that abnormality in GAR increases intragastric pressure (IGP) and conversely enhances early GE (15,25). TRPV2 mRNA was detected throughout the mouse gastrointestinal tract, and TRPV2 immunoreactivity was detected in 84.3% of neuronal nitric oxide synthaseexpressing myenteric neurons in the stomach.…”

Do Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Really Have No Effect on the Gastric Emptying Rate?

“…Some papers have reported that PPIs reduced gastric wall tonus to induce accommodation 8. Regarding the delayed gastric emptying of acid-suppressive drugs, we should be aware of the possibility that PPIs improve gastric reservoir function by reducing gastric tonus.…”