Top

Published in:

01-07-2004 | Experimental

Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine

Authors: Sonja Fruhwald, Eva Herk, Heinz F. Hammer, Peter Holzer, Helfried Metzler

Published in: Intensive Care Medicine | Issue 7/2004

Abstract

Objective: Cerulein and neostigmine are prokinetic drugs whose potency and effective dose range are barely known. The aim of this study was to assess their benefit for normal and compromised peristalsis. Design: In vitro, isolated segments of guinea pig small intestine. Setting : University laboratory. Interventions: Small bowel segments were mounted in tissue baths and luminally perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine; inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the tissue bath. Measurements and results: Peristalsis was quantified via changes in the peristaltic pressure threshold. One-way and two-way analysis of variance (ANOVA) were used for statistical analysis. Cerulein (0.03–100 nM) stimulated normal peristalsis in a concentration-dependent manner and reversed paralysis of peristalsis induced by all inhibitory test drugs to a similar extent. The properistaltic effect of neostigmine was limited to a narrow concentration range (0.03–0.1 µM), whereas concentrations >0.3 µM inhibited peristalsis. Neostigmine more effectively counteracted blockage of peristalsis caused by atropine than that caused by hexamethonium. The inhibitory effects of epinephrine and sufentanil on peristalsis were reversed only at the concentration range of 0.1–0.3 µM neostigmine. Conclusions: Cerulein stimulates normal peristalsis in vitro at a wide concentration range and reverses blockage of peristalsis caused by drugs with a site of action either on the enteric nervous system or intestinal smooth muscle. Neostigmine’s prokinetic effect, to the contrary, is limited to a small concentration range and best seen when peristalsis is depressed by blockage of cholinergic muscle activation.

Kehlet H, Holte K (2001) Review of postoperative ileus. Am J Surg 182:3–10CrossRef

Wattwil M (1989) Postoperative pain relief and gastrointestinal motility. Acta Chir Scand [Suppl] 550:140–145

Clevers GJ, Smout AJ, van der Schee EJ, Akkermans LM (1991) Myoelectrical and motor activity of the stomach in the first days after abdominal surgery: evaluation by electrogastrography and impedance gastrography. J Gastroenterol Hepatol 6:253–259PubMed

Tollesson PO, Cassuto J, Rimback G (1992) Patterns of propulsive motility in the human colon after abdominal operations. Eur J Surg 158:233–236PubMed

Livingston EH, Passaro EP (1990) Postoperative ileus. Dig Dis Sci 35:121–132PubMed

De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Herman AG, Pelckmans PA (1997) Effect of adrenergic and nitrergic blockade on experimental ileus in rats. Br J Pharmacol 120:464–468PubMed

De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Schuurkes JA, Peeters TL, Herman AG, Pelckmans PA (1999) Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats. Gut 45:713–718PubMed

Eskandari MK, Kalff JC, Billiar TR, Lee KK, Bauer AJ (1999) LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity. Am J Physiol 277:478–486

Kalff JC, Schraut WH, Simmons RL, Bauer AJ (1998) Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg 228:652–663CrossRefPubMed

10.

Kalff JC, Carlos TM, Schraut WH, Billiar TR, Simmons RL, Bauer AJ (1999) Surgical-induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus. Gastroenterology 117:378–387PubMed

11.

Kalff JC, Turler A, Schwarz NT, Schraut WH, Lee KK, Tweardy DJ, Billiar TR, Simmons RL, Bauer AJ (2003) Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy. Ann Surg 237:301–315CrossRefPubMed

12.

Zielmann S, Grote R (1995) Auswirkungen der Langzeitsedierung auf die intestinale Funktion. Anaesthesist [Suppl 3] 44:549–558

13.

Kromer W (1990) Endogenous opioids, the enteric nervous system and gut motility. Dig Dis 8:361–373PubMed

14.

Fruhwald S, Scheidl S, Toller W, Petnehazy T, Holzer P, Metzler H, Hammer HF (2000) Low potential of dobutamine and dopexamine to block intestinal peristalsis as compared with other catecholamines. Crit Care Med 28:2893–2897

15.

Fruhwald S, Herk E, Petnehazy T, Scheidl S, Holzer P, Hammer F, Metzler H (2002) Sufentanil potentiates the inhibitory effect of epinephrine on intestinal motility. Intensive Care Med 28:74–80CrossRef

16.

Shahbazian A, Heinemann A, Schmidhammer H, Beubler E, Holzer-Petsche U, Holzer P (2002) Involvement of mu- and kappa-, but not delta-opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea pig intestine. Br J Pharmacol 135:741–750PubMed

17.

Vizi SE, Bertaccini G, Impicciatore M, Knoll J (1973) Evidence that acetylcholine released by gastrin and related polypeptides contributes to their effect on gastrointestinal motility. Gastroenterology 64:268–277PubMed

18.

Dal Forno G, Pietra C, Urciuoli M, van Amsterdam FT, Toson G, Gaviraghi G, Trist D (1992) Evidence for two cholecystokinin receptors mediating the contraction of the guinea pig isolated ileum longitudinal muscle myenteric plexus. J Pharmacol Exp Ther 261:1056–1063PubMed

19.

Holzer P, Shahbazian A, Painsipp E (2003) Evaluation of peristalsis in multiple segments of the guinea-pig isolated small intestine: optimization of tissue use by refined in vitro methodology. Altern Lab Animals 31:419–427

20.

Vincent ME, Wetzner SM, Robbins AH (1982) Pharmacology, clinical uses, and adverse effects of ceruletide, a cholecystokinetic agent. Pharmacotherapy 2:223–234PubMed

21.

Sternini C, Wong H, Pham T, De Giorgio R, Miller LJ, Kuntz SM, Reeve JR, Walsh JH, Raybould HE (1999) Expression of cholecystokinin A receptors in neurons innervating the rat stomach and intestine. Gastroenterology 117:1136–1146PubMed

22.

Sadek SA, Cranford C, Eriksen C, Walker M, Campbell C, Baker PR, Wood RA, Cuschieri A (1988) Pharmacological manipulation of adynamic ileus: controlled randomized double-blind study of ceruletide on intestinal motor activity after elective abdominal surgery. Aliment Pharmacol Ther 2:47–54PubMed

23.

Madsen PV, Olsen O, Hagen K (1986) Ceruletide and neostigmine in postoperative intestinal paralysis. A double-blind clinical controlled trial. Dis Colon Rectum 29:712–713PubMed

24.

Frigo GM, Lecchini S, Marcoli M, Tonini M, D’Angelo L, Crema A (1984) Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation. Naunyn Schmiedebergs Arch Pharmacol 325:145–152PubMed

25.

Holzer P, Lembeck F (1979) Effect of neuropeptides on the efficiency of the peristaltic reflex. Naunyn Schmiedebergs Arch Pharmacol 307:257–264PubMed

26.

Marcoli M, Lecchini S, De Ponti F, D’Angelo L, Crema A, Frigo GM (1985) Subsensitivity of enteric cholinergic neurones to alpha₂-adrenoceptor agonists after chronic sympathetic denervation. Naunyn Schmiedebergs Arch Pharmacol 329:271–277PubMed

27.

Taguchi A, Sharma N, Saleem RM, Sessler DI, Carpenter RL, Seyedsadr M, Kurz A (2001) Selective postoperative inhibition of gastrointestinal opioid receptors. N Engl J Med 345:935–940CrossRefPubMed

28.

Tonini M, Costa M (1990) A pharmacological analysis of the neuronal circuitry involved in distension-evoked enteric excitatory reflex. Neuroscience 38:787–795PubMed

29.

Holzer P, Lippe IT, Heinemann A, Bartho L (1998) Tachykinin NK₁ and NK₂ receptor-mediated control of peristaltic propulsion in the guinea-pig small intestine in vitro. Neuropharmacology 37:131–138CrossRefPubMed

30.

Prasad M, Matthews JB (1999) Deflating postoperative ileus. Gastroenterology 117:489–492PubMed

31.

Myrhoj T, Olsen O, Wengel B (1988) Neostigmine in postoperative intestinal paralysis. A double-blind, clinical, controlled trial. Dis Colon Rectum 31:378–379PubMed

32.

Kreis ME, Kasparek M, Zittel TT, Becker HD, Jehle EC (2001) Neostigmine increases postoperative colonic motility in patients undergoing colorectal surgery. Surgery 130:449–456CrossRefPubMed

33.

van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF (2001) Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure—a prospective, double-blind, placebo-controlled trial. Intensive Care Med 27:822–827CrossRef

34.

Davison SC, Hyman N, Prentis RA, Dehghan A, Chan K (1980) The simultaneous monitoring of plasma levels of neostigmine and pyridostigmine in man. Methods Find Exp Clin Pharmacol 2:77–82PubMed

Title: Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine
Authors: Sonja Fruhwald
Eva Herk
Heinz F. Hammer
Peter Holzer
Helfried Metzler
Publication date: 01-07-2004
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 7/2004
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-004-2317-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2004

Incomplete protection by prophylactic surfactant against the adverse effects of large lung inflations at birth in immature lambs

Blind and bronchoscopic sampling methods in suspected ventilator-associated pneumonia

Author’s reply to the comments by de Rooij and de Jonge

Acute respiratory distress syndrome (ARDS) and low tidal volume ventilation: the debate about weight

Noninvasive vs invasive ventilation in COPD patients with severe acute respiratory failure deemed to require ventilatory assistance

Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity