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A tachykinin antagonist inhibits gastric emptying and gastrointestinal transit in the rat.

The effect of a substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr. Examination 15 min after the test meal showed that SPA (0.13-1.3 mumol kg-1) inhibited gastric emptying and gastrointestinal transit in a dose-dependent manner. The inhibitory effect of SPA on gastric emptying and gastrointestinal transit remained unchanged after pretreatment of rats with mepyramine (8.7 mumol kg-1) plus cimetidine (19.8 mumol kg-1) or with guanethidine (67 mumol kg-1). Since a full examination of SPA as a specific tachykinin antagonist was not possible in vivo, SPA was also tested on circular muscle strips from the rat gastric corpus in vitro. Submaximal contractions in response to bombesin or bethanechol were not reduced by SPA (50 microM), whereas those in response to substance P were inhibited. The results suggest that SPA inhibits gastric emptying and gastrointestinal transit by interfering with the action of tachykinins released from enteric nerves and that endogenous tachykinins are involved in the regulation of gastrointestinal motility.

Animals↗

Therapeutic strategies for motility disorders. Medications, nutrition, biofeedback, and hypnotherapy.

Gastrointestinal motility is regulated by a complex balance of inhibitory and excitatory neuronal, humoral, and mechanical factors. The goal in the management of motility disorders is to maintain adequate nutrition while decreasing symptoms. This can be accomplished by medications and support of nutrition and biofeedback; the application of these therapeutic strategies to patients with gut motility disorders is reviewed.

Biofeedback, Psychology↗

A novel tachykinin NK2 receptor antagonist prevents motility-stimulating effects of neurokinin A in small intestine.

1. MEN 11420 (nepadutant) is a potent, selective and competitive antagonist of tachykinin NK2 receptors. 2. The objective of the present study was to assess the capability of the drug to antagonize the stimulatory effects of neurokinin A (NKA) on gastrointestinal motility, as well as to change the fasting migrating motor complex (MMC). 3. Thirty-four male volunteers were randomized to treatment with either placebo or MEN 11420 in a double-blinded manner. Effects of MEN 11420 (8 mg intravenously) were evaluated as changes in phases I, II and III of MMC, as well as contraction frequency, amplitude and motility index during baseline conditions and during stimulation of motility using NKA (25 pmol kg(-1) min(-1) intravenously). 4. NKA preceded by placebo increased the fraction of time occupied by phase II, increased contraction frequency, amplitude and motility index. 5. MEN 11420 effectively antagonized the motility-stimulating effects of NKA. MEN 11420 reduced the phase II-stimulating effect of NKA. In addition, the stimulatory effect of NKA on contraction frequency and amplitude, as well as motility index were inhibited by MEN 11420. MEN 11420 did not affect the characteristics of MMC during saline infusion. 6. Plasma levels of MEN 11420 peaked during the first hour after infusion and decreased to less than half during the first 2 h. 7. In conclusion, intravenous MEN 11420 effectively inhibited NKA-stimulated, but not basal gastrointestinal motility, and was well tolerated by all subjects.

Abdominal Pain↗

Gastrointestinal promotility drugs in the critical care setting: a systematic review of the evidence.

CONTEXT: Gastrointestinal promotility agents may improve tolerance to enteral nutrition, reduce gastroesophageal reflux and pulmonary aspiration, and therefore have the potential to improve outcomes of critically ill patients. OBJECTIVE: To systematically review and critically appraise studies of promotility agents in the critical care setting. DATA SOURCES: Computerized bibliographic search of published research (1980-2001), citation review of relevant articles, and contact with primary investigators. STUDY SELECTION: Randomized trials of critically ill adult patients that evaluated the effect of promotility agents on measures of gastrointestinal motility were included. DATA EXTRACTION: Relevant methods and outcome data were abstracted in duplicate by independent investigators. DATA SYNTHESIS: We reviewed 60 citations; 18 articles met the inclusion criteria (six studies of feeding tube placement, 11 studies evaluating gastrointestinal function, and one study of clinical outcomes). The heterogeneity of study methods and outcomes measured precluded a quantitative synthesis of the data. Although there are conflicting studies, the larger and more methodologically robust studies suggest that metoclopramide has no effect on feeding tube placement. Erythromycin has been shown to increase success rates with small-bowel tube placement in two studies. Eight of ten studies evaluating the effect of cisapride, metoclopramide, or erythromycin on measures of gastrointestinal transit demonstrated positive effects; the two studies that did not were relatively small (n = 27 and 10) and likely had inadequate power to detect a difference in treatment effect. No study demonstrated a positive effect on clinical outcomes. CONCLUSIONS: As a class of drugs, promotility agents appear to have a beneficial effect on gastrointestinal motility in critically ill patients. A one-time dose of erythromycin may facilitate small-bowel feeding tube insertion. Administration of metoclopramide appears to increase physiologic indexes of gastrointestinal transit and feeding tolerance. Concerns about safety and lack of effect on clinically important outcomes preclude strong treatment recommendations.

Critical Care↗

Contraction of canine stomach and small bowel by intravenous administration of serotonin. A physiologic response?

Serotonin is found in large quantities in the gastrointestinal tract, where it can increase gastrointestinal motility. Whether this response represents a physiologic event has not previously been shown. In our investigation eight conscious dogs were fitted with strain gauges to monitor motility responses to serotonin. When infused intravenously, serotonin significantly increased the contraction rate and force of canine stomach, small bowel, and isolated Thirty-Vella loops. Whole blood serotonin levels monitored by radioimmunoassay showed no significant increase in levels during these infusions. Serotonin may have a physiologic function in the mediation of gastrointestinal motility.

Animals↗

The effect of intrathecal medetomidine on small bowel transit in the rat.

BACKGROUND AND OBJECTIVE: Gastrointestinal motility is influenced by abdominal trauma, laparotomy and particularly by intestinal ischaemia. The reflex inhibition of gastrointestinal motility is mediated mainly by the sympathetic nervous system. There are reports on the effects of systemically applied alpha2-adrenoceptor agonists on gastric emptying and recovery of bowel motility, but the effect of spinally applied alpha2-adrenoceptor agonists on intestinal motility has not been studied. The aim of this study was to investigate the effects of intrathecal medetomidine on gastrointestinal transit in rats after transient intestinal ischaemia. METHODS: Forty rats were randomly assigned to four groups of 10 each. Intrathecal catheter insertion and laparotomy were performed on each rat. Saline (10 microL) was injected intrathecally in Groups A and B. Medetomidine (10 microg in 10 microL) was injected intrathecally in Groups C and D. Intestinal ischaemia was induced in Groups B and D. Gastrointestinal transit was determined by measuring the length that a standardized marker meal of activated charcoal had travelled. Intrathecal medetomidine was compared to intrathecal saline in their effect on intestinal motility after 30 min period of bowel ischaemia. RESULTS: Laparotomy and intestinal ischaemia slowed gastrointestinal transit. Intrathecal medetomidine accelerated transit in both ischaemia and non-ischaemia groups. CONCLUSION: Intrathecal medetomidine markedly accelerated small intestinal transit and may also hasten the recovery from post-ischaemic paralytic ileus.

Analgesics, Non-Narcotic↗

Gastrointestinal motor activity after pylorus-preserving gastrectomy with or without vagotomy in dogs.

BACKGROUND: In the present study we evaluated gastrointestinal motility after gastrectomy of a new pylorus-preserving technique that is becoming a popular operation for early stage carcinoma of the stomach. STUDY DESIGN: Using strain-gauge force transducers we studied gastrointestinal motility in control dogs, dogs after pylorus-preserving gastrectomy, and dogs after conventional distal gastrectomy with Billroth I reconstruction. Dogs with gastrectomy were reoperated upon after recording motility patterns, and the effect of vagal denervation of the gastric remnant on motility was investigated. Overall motility pattern, length of the digestive phase in the jejunum, and interval of the interdigestive phase III contractions were studied and compared among the three groups. RESULTS: In dogs after gastrectomy without vagal denervation, the regular occurrence of interdigestive phase III contractions from the gastric remnant to the jejunum was identified. In dogs after gastrectomy with vagal denervation, however, no apparent interdigestive phase III contractions were observed in the gastric remnant. The duration of the digestive phase in the jejunum, which correlates with postprandial gastric emptying, was not different between the control dogs and the dogs having pylorus-preserving gastrectomy. However, this duration was significantly shorter in dogs having conventional distal gastrectomy compared with the control dogs, not only before but after vagal denervation. CONCLUSIONS: These results indicate that the postoperative motor function after pylorus-preserving gastrectomy may be superior to that after conventional distal gastrectomy with Billroth I reconstruction.

Animals↗

Comparison of the inhibitory efficacy of four belladonna drugs on gastrointestinal movement and cognitive function in food-deprived mice.

Belladonna drugs, scopolamine (Sco), atropine (Atr), anisodine (AT(3)), and anisodamine (Ani), frequently used for gastrointestinal motility disorders often produce adverse effects on the central nervous system. In the present work, these drugs (0.05, 0.5, 5, and 50 micromol kg(-1), i.p.) were evaluated for their potential to inhibit gastrointestinal motility and cognition in mice. Results showed that the maximum inhibitory rates of Sco, Atr, AT(3), and Ani on gastric emptying and small intestinal movement were 29.78, 40.69, 12.30, and 17.99% and 51.98, 58.46, 46.51, and 46.22%, respectively. The affinities of Sco, Atr, AT(3), and Ani for muscarinic receptors in the whole mice were 1.62, 1.48, 2.28, and 1.11 micromol kg(-1) for the stomach or 0.30, 1.12, 0.59, and 1.14 micromol kg(-1) for the small intestine, respectively. The minimal effective doses for impairing avoidance-response learning were 5 micromol kg(-1) for Sco, Atr, or AT(3) and 50 micromol kg(-1) for Ani. The initial doses for insulting the avoidance-response memory or open-field memory were 0.5, 5, 5, and 50 micromol kg(-1) or 5, 5, 5, and >50 micromol kg(-1) for Sco, Atr, AT(3), and Ani, respectively. We conclude that the relative susceptibility of the mouse's tissue or function capacities towards the inhibitory effects of belladonna drugs is small intestine > stomach > avoidance-response memory > avoidance-response learning > open-field memory.

Animals↗

The effect of propofol on human gastric and colonic muscle contractions.

UNLABELLED: Although propofol is widely used for sedation in the intensive care unit, there are limited data on its effects on gastrointestinal motility. For that reason, we studied the in vitro effects of propofol on human gastric and colonic smooth muscle. Grossly normal human gastric and colonic muscle strips were mounted in an organ bath set-up for isometric contraction and stimulated by acetylcholine (Ach), using a cumulative dose schedule in the absence or presence of different concentrations of propofol [1.7 x 10(-6) M (0.3 microg/mL) to 4.4 x 10(-4) M (78 microg/mL)]. Ach led to concentration-dependent contraction of both gastric and colonic muscle strips, whereas propofol, at a concentration 6.7 x 10(-6) M (1.2 microg/mL) and above, significantly depressed Ach-induced contraction in a concentration-dependent manner for both smooth muscle preparations. In addition, propofol, at a concentration 2.7 x 10(-5)M (4.8 microg/mL) and above, depressed spontaneous contractile activity of both smooth muscle preparations. Fat emulsion 10% (Intralipid), the solvent for propofol, had no effect on either the spontaneous activity or the Ach-induced contraction of gastric and colonic smooth muscles. IMPLICATIONS: The success of enteral feeding requires a normal gastrointestinal motility. We found that, at clinically relevant concentrations, propofol impaired gastrointestinal contractile activity. Further investigations are required to determine the clinical significance of this change.

Acetylcholine↗

[Galanin: a new biologically active gastrointestinal neuropeptide].

The 29 amino acid containing neuropeptide galanin is localized in the intrinsic nervous system of the entire gastrointestinal tract and the pancreas. It was found in man and several animal species. Molecular biology studies revealed different molecular forms of galanin in several mammalian species including man. The galanin precursor was also found. Galanin shows several potent pharmacological actions: it inhibits gastrointestinal motility in man. It also has an inhibitory effect on intestinal smooth muscle contractility of several animal species. These actions are mediated directly by opening of potassium channels and indirectly by inhibition of acetylcholine release. In addition galanin inhibits pancreatic hormone secretion (i.e. hypoinsulinemia, hyperglycemia) and partly the release of hormones localized in the gastrointestinal tract. On exocrine glands in man (salivary glands) galanin has hydrokinetic actions. The physiological role of galanin might be regulation of gastrointestinal motility, control of secretory function of intestine and a regulatory role in endocrine and exocrine gland secretion.

Animals↗

Interdigestive migrating contraction in short bowel dogs.

Extraluminal force transducers were chronically implanted onto the serosal surface of the gastrointestinal tract in dogs and the interdigestive migrating contractions (IMC) were studied in conscious dogs. When the IMC occurring periodically in the stomach reaches the distal ileum, the next IMC develops in the stomach. We therefore studied the effect of isolation or resection of the lower third of the small bowel on the periodic occurrence of IMC in the stomach. Transducers were sutured onto the antrum, the upper jejunum, the mid intestine and the terminal ileum. After control records on gastrointestinal motility were made for these dogs, the abdominal cavity was again opened to prepare a Thiry loop in the lower third of the small bowel. (isolation group) Next, the loop was removed (resection group) and gastrointestinal motility was recorded. In these groups, we 1) measured the time from the feeding to the initiation of the first IMC. 2) measured the time from the termination of one IMC to the termination of the next IMC. 3) measured the migrating time of the IMC. 4) and measured the duration of the IMC in the stomach. As a result, it was found that the time interval between the termination of one IMC in the stomach and the termination of the next was almost constant throughout all experiments. The migrating time of the IMC from the stomach to the terminal ileum in isolation and resection groups was slightly shortened. These findings indicate that the existence of the lower gut has no significant influence upon the regular periodic occurrence of the IMC in the stomach and the migrating time.

Animals↗

Neostigmine increases postoperative colonic motility in patients undergoing colorectal surgery.

BACKGROUND: Gastrointestinal motility is frequently impaired after abdominal surgery. We investigated the effects of neostigmine on colonic motility in patients after colorectal surgery and in healthy volunteers. METHODS: Colonic motility was recorded by a manometry/barostat system in 12 patients after left colonic or rectal resection during baseline and after the intravenous administration of increasing doses of neostigmine on postoperative days 1, 2, and 3. In addition, colonic motility was recorded in 7 healthy volunteers. RESULTS: Neostigmine increased the colonic motility index. This increase was from 135 +/- 28 mm Hg/min at baseline to 574 +/- 219 mm Hg/min after administration of 5 microg/kg neostigmine on day 3 after surgery (mean +/- SEM, P <.05). In healthy volunteers, neostigmine at a dose of 5 microg/kg increased the colonic motility index from 184 +/- 73 to 446 +/- 114 mm Hg/min (P <.05). Barostat bag volumes decreased dose-dependently after neostigmine administration in patients as well as in volunteers, indicating an increase in colonic tone. CONCLUSIONS: Colonic motility and tone increased after neostigmine administration at a dose of 5 microg/kg in postoperative patients and in healthy volunteers. Neostigmine can be used to stimulate colonic motility after colorectal surgery and has a similar effect postoperatively as in healthy volunteers.

Adult↗