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- MATERIALS AND METHODS
Somatostatin and its analogue octreotide influence gastrointestinal motility and secretion.1–3 Both inhibit gastric acid and pancreatic enzyme secretion, gall-bladder contraction and delay intestinal transit. Recent studies indicate that octreotide affects visceral perception by increasing the threshold for symptoms during balloon distension. This has been demonstrated for rectal and colonic perception both in healthy subjects and patients with irritable bowel syndrome.3–6 Octreotide influences perception through inhibition of the spinal afferent pathway.4, 6
Little is known about the effect of somatostatin on proximal gastric motor function and symptom perception. Only Mertz et al.,7 using the long-acting somatostatin analogue octreotide, found the gastric accommodation reflex to be reduced, resulting in a less compliant proximal stomach. Octreotide also had an inhibitory effect on the perception of fullness in response to low volume distensions. The aim of our study was to investigate the effect of native somatostatin during continuous intravenous infusion on the motor function of the proximal stomach and visceral perception during volume and pressure distensions. The function of the proximal stomach was measured with an electronic barostat.
- Top of page
- MATERIALS AND METHODS
We have shown that somatostatin does not influence compliance of the proximal stomach but it does decrease perception of abdominal pressure and fullness during graded distensions. Somatostatin also caused a reduction in phasic volume waves to almost zero immediately after the start of infusion.
The compliance of the proximal stomach was not significantly influenced by somatostatin during either volume or pressure distensions. Little is known about the effect of somatostatin on proximal gastric motor function. Koerker & Hansen have shown in monkeys that somatostatin does not influence intragastric pressure and antral contractions.13 Others have reported an inhibitory effect of somatostatin on gastric motility.14 However, it is not clear from this study whether motility in the proximal or in the distal part of the stomach was reduced. Mertz et al.,7 using the somatostatin analogue octreotide, showed that octreotide reduced the rate of the gastric accommodation reflex by 50%, resulting in a reduced compliance at distension pressures greater than 10 mmHg. However, this effect was observed only during phasic distension and not during ramp distension. Our results, i.e. that somatostatin does not affect proximal gastric compliance during stepwise increasing pressure distension, are in line with those of Mertz et al.7 during ramp distension. Depending on the type of gastric distension, different mechanoreceptors are activated.7 Somatostatin can influence gastrointestinal motility through direct neural pathways or by inhibition of secretion of gastrointestinal peptides or hormones.
Results on the effect of somatostatin on gastric emptying are conflicting. Whereas some studies have shown acceleration, others have found gastric emptying to be delayed. Somatostatin inhibits antral motility, which is thought to result in a delay of gastric emptying of solids. In the study by Haruma et al.,15 a single dose of octreotide of 50 μg s.c. significantly reduced postprandial motility of the distal antrum. Okamoto et al.16 demonstrated that octreotide at a dose of 50 μg s.c. delayed gastric emptying of a liquid meal, but did not affect antral motility. The effect of octreotide on gastric emptying occurred in a biphasic pattern. During the first hour gastric emptying was accelerated, but in the late postprandial phase gastric emptying was significantly delayed.16 During the solid meal, octreotide decreased antral contractility through a reduction in the mean amplitude but not by influencing the frequency of contractions. Recently Von der Ohe et al. also found that octreotide resulted in a faster initial emptying of solids from the stomach.2 They suggested that this finding is a result of the inhibitory effect of somatostatin on gastric secretion, which makes the total intragastric volume smaller and gastric emptying faster. Apart from antral motility, however, proximal gastric motor function, pyloric contractions and antroduodenal coordination also determine the rate of gastric emptying. In our study proximal gastric motor function was not influenced by somatostatin and this cannot explain alterations in gastric emptying in response to somatostatin or octreotide. Pylorospasm has been reported after octreotide and may contribute to delayed gastric emptying.17 Somatostatin significantly reduced the frequency and amplitude of phasic volume events. These rapid changes in volume of the bag during constant bag pressure (minimal distending pressure + 2 mmHg) may reflect phasic contractions of the gut. However, the clinical relevance of this is not yet fully understood. After meal ingestion a reduction in volume wave frequency has also been observed.
During continuous intravenous infusion of somatostatin, perception of abdominal pressure and fullness in response to distensions was inhibited. These results are in line with previous studies using the somatostatin analogue octreotide and showing inhibitory effects on the perception of abdominal symptoms in healthy subjects and subjects with functional gastrointestinal disorders.4–7 Bradette et al. showed that octreotide increased the threshold of colonic visceral perception in patients with irritable bowel syndrome without modifying muscle tone.5 Mertz et al. showed that during phasic and ramp distension of the proximal stomach, octreotide increased the threshold for fullness (innocuous sensation), while the volume threshold for pain (noxious sensation) was decreased during phasic distension.7 The hyperalgesic effect was explained as being secondary to the inhibitory effect of octreotide on the gastric accommodation reflex.7
Visceral sensitivity is controlled either in peripheral receptors in the spinal cord by altering signal processing in the dorsal horn or second-order neurons, or in the higher centres above the brain stem, where conscious perception occurs. Mechanoreceptors in the stomach are located in the non-mucosal layer of the gastric wall and use both vagal and splanchnic afferents. These receptors respond to contraction and distension.18 It is thought that somatostatin and octreotide inhibit visceral perception directly by inhibiting these afferent pathways. This has been investigated for rectal perception. Hasler et al. have shown that octreotide reduces the sensation of rectal distension via inhibition of visceral afferent pathways.4 Chey et al. showed that octreotide reduces perception of rectal electrical stimulation by spinal afferent inhibition.6
Previous studies have shown that visceral perception is increased in patients with functional dyspepsia.19, 20 Therefore it would be interesting to further evaluate the effect of somatostatin and of octreotide in patients with functional dyspepsia.
In summary, continuous infusion of somatostatin does not influence human gastric compliance, but inhibits phasic volume waves and significantly reduces visceral perception.