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

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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.

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References

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

    Article  Google Scholar 

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

    Google Scholar 

  3. 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 6:253–259

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. 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 120:464–468

    PubMed  Google Scholar 

  7. 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 45:713–718

    PubMed  Google Scholar 

  8. 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

    Google Scholar 

  9. 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 228:652–663

    Article  CAS  PubMed  Google Scholar 

  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 117:378–387

    CAS  PubMed  Google Scholar 

  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 237:301–315

    Article  PubMed  Google Scholar 

  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 8:361–373

    CAS  PubMed  Google Scholar 

  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

    Google Scholar 

  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 28:74–80

    Article  Google Scholar 

  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 135:741–750

    CAS  PubMed  Google Scholar 

  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 64:268–277

    CAS  PubMed  Google Scholar 

  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 261:1056–1063

    PubMed  Google Scholar 

  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

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  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 117:1136–1146

    CAS  PubMed  Google Scholar 

  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 2:47–54

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  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 325:145–152

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  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 329:271–277

    CAS  PubMed  Google Scholar 

  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 345:935–940

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  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 37:131–138

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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 27:822–827

    Article  Google Scholar 

  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 2:77–82

    CAS  PubMed  Google Scholar 

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Acknowledgement

This study was supported by a grant from the Jubilee Funds of the Austrian National Bank

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Authors and Affiliations

  1. Department of Anaesthesiology and Intensive Care Medicine, University of Graz, Auenbruggerplatz 29, 8036, Graz, Austria

    Sonja Fruhwald, Eva Herk & Helfried Metzler

  2. Department of Internal Medicine, University of Graz, Graz, Austria

    Heinz F. Hammer

  3. Department of Experimental and Clinical Pharmacology, University of Graz, Graz, Austria

    Peter Holzer

Authors
  1. Sonja Fruhwald
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  2. Eva Herk
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  3. Heinz F. Hammer
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  4. Peter Holzer
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  5. Helfried Metzler
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Correspondence to Sonja Fruhwald.

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Fruhwald, S., Herk, E., Hammer, H.F. et al. Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine. Intensive Care Med 30, 1414–1420 (2004). https://doi.org/10.1007/s00134-004-2317-2

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  • DOI: https://doi.org/10.1007/s00134-004-2317-2

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