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. 1999 Nov;45(5):713–718. doi: 10.1136/gut.45.5.713

Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats

B Y De Winter 1, G Boeckxstaens 1, J G De Man 1, T Moreels 1, J Schuurkes 1, T Peeters 1, A Herman 1, P Pelckmans 1
PMCID: PMC1727718  PMID: 10517907

Abstract

BACKGROUND/AIM—The effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with that of granisetron, a 5-hydroxytryptamine (5-HT3) receptor antagonist, and a novel enterokinetic agent, prucalopride, a 5-HT4 receptor agonist.
METHODS—Different degrees of inhibition of gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy, or laparotomy plus mechanical stimulation of the gut.
RESULTS—Metoclopramide decreased the transit after laparotomy with or without mechanical stimulation, whereas cisapride increased it after all three operations. Granisetron had no effect on the transit after the three operations when given alone. Prucalopride tended to increase the transit after laparotomy with or without mechanical stimulation when given alone. However, statistical significance was only reached when prucalopride was combined with granisetron. Erythromycin, a motilin receptor agonist, did not improve postoperative ileus in the rat.
CONCLUSIONS—Cisapride, but not metoclopramide or erythromycin, is able to improve postoperative ileus in the rat. The results suggest that a combination of 5-HT3 receptor antagonist and 5-HT4 receptor agonist properties may be required to obtain a beneficial effect on surgery induced ileus in the rat. Furthermore, they indirectly indicate that stimulation of the excitatory mechanisms is not able to overcome the inhibitory influence of the neural reflex pathways activated during abdominal surgery.


Keywords: ileus; motilin; cisapride; metoclopramide; 5-HT3 receptor; 5-HT4 receptor

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Figure 1  .

Figure 1  

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Effect of skin incision (SI), laparotomy (LAP), or laparotomy plus mechanical stimulation of the small intestine and caecum (L+M) on intestinal transit in control rats (n = 9-10) and rats treated with metoclopramide (30 mg/kg; n = 9) or cisapride (1 mg/kg; n = 9-10). Results are expressed as cm migration of Evans blue and shown as mean (SEM). *Significantly different from the transit in control rats with the same operation (p⩽0.05); †significantly different from the transit in rats treated with metoclopramide with the same operation (p⩽0.05) (one way analysis of variance followed by the Bonferroni test).

Figure 2  .

Figure 2  

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Effect of skin incision (SI), laparotomy (LAP), or laparotomy plus mechanical stimulation of the small intestine and caecum (L+M) on intestinal transit in control rats (n = 9-10) and rats treated with granisetron 10 µg/kg (n = 9) or 50 µg/kg (n = 9-10). Results are expressed as cm migration of Evans blue and shown as mean (SEM). One way analysis of variance could not detect any significant differences between the treatment groups.

Figure 3  .

Figure 3  

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Effect of skin incision (SI), laparotomy (LAP), or laparotomy plus mechanical stimulation of the small intestine and caecum (L+M) on intestinal transit in control rats (n = 9) and in rats treated with prucalopride 1 mg/kg (n = 9) or 5 mg/kg (n = 9). Results are expressed as cm migration of Evans blue and shown as mean (SEM). *Significantly different from the transit in control rats after laparotomy (p⩽0.05) (one way analysis of variance followed by the Bonferroni test).

Figure 4  .

Figure 4  

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Effect of skin incision (SI), laparotomy (LAP), or laparotomy plus mechanical stimulation of the small intestine and caecum (L+M) on intestinal transit in control rats (n = 10) and rats treated with a combination of granisetron (50 µg/kg) and prucalopride (1 mg/kg) (n = 9-10). Results are expressed as cm migration of Evans blue and shown as mean (SEM). *Significantly different from the transit in control rats with the same operation (p⩽0.05) (unpaired Student's t test).

Figure 5  .

Figure 5  

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Effect of skin incision (SI), laparotomy (LAP), or laparotomy plus mechanical stimulation of the small intestine and caecum (L+M) on intestinal transit in control rats (n = 9) and rats treated with erythromycin (1 mg/kg; n = 9). Results are expressed as cm migration of Evans blue and shown as mean (SEM). Unpaired Student's t test could not detect any significant differences between the treatment groups.

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