Yonsei Med J.  2013 Jul;54(4):845-853. 10.3349/ymj.2013.54.4.845.

The Effects of Prucalopride on Postoperative Ileus in Guinea Pigs

• Park SJ
• Choi EJ
• Yoon YH
• Park H

• KMID: 2158217
• DOI: http://doi.org/10.3349/ymj.2013.54.4.845

Abstract

PURPOSE
Postoperative ileus (POI) is an impairment of coordinated gastrointestinal (GI) motility that develops as a consequence of abdominal surgery and is a major factor contributing to patient morbidity and prolonged hospitalization. The aim of this study was to investigate the effects of different 5-hydroxytryptamine 4 (5-HT4) receptor agonists, which stimulate excitatory pathways, on a POI model.
MATERIALS AND METHODS
The experimental model of POI in guinea pigs was created by laparotomy, gentle manipulation of the cecum for 60 seconds, and closure by suture, all under anesthesia. Different degrees of restoration of GI transit were measured by the migration of charcoal. Colonic transit was indirectly assessed via measurement of fecal pellet output every hour for 5 hours after administration of various doses of mosapride, tegaserod, prucalopride, and 5-HT.
RESULTS
Charcoal transit assay showed that various 5-HT4 receptor agonists can accelerate delayed upper GI transit in a dose-dependent manner. However, fecal pellet output assay suggested that only prucalopride had a significant effect in accelerating colonic motility in POI.
CONCLUSION
Although mosapride, tegaserod, and prucalopride produce beneficial effects to hasten upper GI transit in the POI model, prucalopride administered orally restores lower GI transit as well as upper GI transit after operation in a conscious guinea pig. This drug may serve as a useful candidate for examination in a clinical trial for POI.

Keyword

Postoperative ileus; 5-HT4 receptor agonist; gastrointestinal transit; prucalopride

MeSH Terms

Administration, Oral
Animals
Benzamides/pharmacology
Benzofurans/administration & dosage/*pharmacology
Charcoal/pharmacokinetics
Colon/drug effects
Dose-Response Relationship, Drug
Gastrointestinal Motility/*drug effects
Guinea Pigs
Ileus/*surgery
Indoles/pharmacology
Laparotomy
Male
Morpholines/pharmacology
Postoperative Complications/drug therapy
Serotonin/pharmacology
Serotonin 5-HT4 Receptor Agonists/*pharmacology
Benzamides
Benzofurans
Indoles
Morpholines
Serotonin 5-HT4 Receptor Agonists
Charcoal
Serotonin

Figure

• 

  Fig. 1 Radiologic images of postoperative ileus in a guinea pig model. The level of gas distention peaked at 3 hours after the operation (arrow).

• 

  Fig. 2 Results of the charcoal transit assay with various doses of mosapride, tegaserod, prucalopride, and 5-HT compared to postoperative ileus (POI), anesthesia, and sham operation groups. *Significant p value in prucalopride (10 mg/kg) group compared to POI and prucalopride (0.5 mg/kg) groups after Bonferroni analysis. †Significant p value in mosapride (10 mg/kg) group compared to POI and mosapride (1 mg/kg) groups after Bonferroni analysis. ‡Significant p value in anethesia and sham operation groups compared with POI group after Bonferroni analysis. ††Significant p value in tegasored (10 mg/kg) group compared to POI and tegaserod (1 mg/kg) groups after Bonferroni analysis. 5-HT, 5-hydroxytryptamine.

• 

  Fig. 3 Results of fecal expulsion assay with the maximal doses (10 mg/kg-1) of each drug. (A) Cumulative fecal weights (g). (B) Cumulative numbers of fecal pellets. *Significant p value compared with POI group. POI, postoperative ileus; 5-HT, 5-hydroxytryptamine.

• 

  Fig. 4 The effects of mosapride on increasing cumulative fecal weight (g) and pellet number at each time-point, compared to the 'anestheia' and 'POI' groups. (A) Cumulative fecal weights (g). (B) Cumulative numbers of fecal pellets. *Significant p value compared with the same time-point in the 'POI' group. POI, postoperative ileus.

• 

  Fig. 5 The effects of tegaserod on increasing cumulative fecal weight (g) and pellet number at each time-point, compared to the 'anestheia' and 'POI' groups. (A) Cumulative fecal weights (g). (B) Cumulative numbers of fecal pellets. *Significant p value compared with the same time-point in the 'POI' group. POI, postoperative ileus.

• 

  Fig. 6 The effects of 5-HT on increasing cumulative fecal weight (g) and pellet number at each time-point, compared to the 'anestheia' and 'POI' groups. (A) Cumulative fecal weights (g). (B) Cumulative numbers of fecal pellets. *Significant p value compared with the same time-point in the 'POI' group. POI, postoperative ileus; 5-HT, 5-hydroxytryptamine.

• 

  Fig. 7 The effects of prucalopride on increasing cumulative fecal weight (g) and pellet number at each time-point, compared to the 'anestheia' and 'POI' groups. (A) Cumulative fecal weights (g). (B) Cumulative numbers of fecal pellets. *Significant p value compared with the same time-point in the 'POI' group. POI, postoperative ileus.

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