Skip to main content
SpringerLink
Log in

The influence of NSAIDs on experimental intestinal anastomoses

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

Limiting degradation of collagen during the initial phase of wound healing is expected to improve postoperative intestinal strength and thereby decrease chances for anastomotic dehiscence. We studied the influence of four nonsteroid anti-inflammatory drugs on the healing of intestinal anastomoses in rats, with special regard to changes of collagen levels around the anastomoses. Four experimental groups of 20 rats each received daily oral doses of piroxicam, ibuprofen, aspirin, or indomethacin and were compared with a control group. Animals were sacrificed 3 or 7 days after operation. Both morbidity and mortality rate in the experimental groups were high. Collagen, measured as hydroxyproline, levels in anastomotic and adjoining 1-cm intestinal segments were compared with concentrations in control segments resected during operation. After an initial decrease on day 3, hydroxyproline concentrations increased on day 7. In the colon the lowering of hydroxyproline concentrations, which was more pronounced than in the ileum, was significantly reduced by administration of piroxicam and ibuprofen, both in the anastomosis and its proximal segment. On day 7, the increase of hydroxyproline concentrations in the ileum was inhibited by administration of anti-inflammatory drugs. It is concluded that nonsteroidal anti-inflammatory drugs may limit postoperative degradation of collagen in colonic anastomoses, but at the same time may increase the rat's susceptibility to surgical infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ballantyne GH. The experimental basis of intestinal suturing: effect of surgical technique, inflammation, and infection on enteric wound healing. Dis Colon Rectum 1984;27:61–71.

    PubMed  Google Scholar 

  2. Gabella G. The cross-ply arrangement of collagen fibres in the submucosa of the mammalian small intestine. Cell Tissue Res 1987;248:491–7.

    PubMed  Google Scholar 

  3. Hunt TK, Hawley PR, Hale J, Goodson W, Thakral KK. Colon repair: the collagenous equilibrium. In: Hunt TK, ed. Wound healing and wound infection. New York: Appelton-Century-Crofts, 1980:153–9.

    Google Scholar 

  4. Hendriks T, Vereecken TH, Hesp WL, Schillings PH, de Boer HH. Loss of collagen from experimental intestinal anastomoses: early events. Exp Mol Pathol 1985;42:411–8.

    PubMed  Google Scholar 

  5. Högström H, Haglund U. Postoperative decrease in suture holding capacity in laparotomy wounds and anastomoses. Acta Chir Scand 1985;151:533–5.

    PubMed  Google Scholar 

  6. Peacock EE, van Winkle W. The biochemistry and the environment of wounds and their relation to wound strength. In: Peacock EE, van Winkle W, eds. Wound repair, 2nd ed. Philadelphia: WB Saunders, 1976:145–203.

    Google Scholar 

  7. Horwitz AL, Hance AJ, Crystal RG. Granulocyte collagenase: selective digestion of type I relative to type III collagen. Proc Natl Acad Sci USA 1977;74:897–901.

    PubMed  Google Scholar 

  8. Werb Z, Gordon S. Secretion of a specific collagenase by stimulated macrophages. J Exp Med 1975;142:346–60.

    PubMed  Google Scholar 

  9. Abramson S, Edelson H, Kaplan H, Given W, Weissman G. The inactivation of the polymorphonuclear leukocyte by nonsteroidal anti-inflammatory drugs. Inflammation 1984;8(suppl):103–8.

    Google Scholar 

  10. Goodwin JS. Immunologic effects of nonsteroidal antiinflammatory drugs. Am J Med 1984;77:7–15.

    Google Scholar 

  11. Hesp FL, Hendriks T, Lubbers EC, de Boer HH. Wound healing in the intestinal wall: a comparison between experimental ileal and colonic anastomoses. Dis Colon Rectum 1984;27:99–104.

    PubMed  Google Scholar 

  12. De Roy van Zuidewijn DB, Wobbes Th, Hendriks T, Klompmakers AA, de Boer HH. The effect of antineoplastic agents on the healing of small intestinal anastomoses in the rat. Cancer 1986;58:62–6.

    PubMed  Google Scholar 

  13. Mastboom WJ, Hendriks T, de Boer HH. Collagen changes around intestinal anastomoses in germ-free rats. Br J Surg 1989;76:797–801.

    PubMed  Google Scholar 

  14. Owen DB. Handbook of statistical tables. Reading, MA: Addison-Wesley, 1964:41–5.

    Google Scholar 

  15. Higgs GA, Eakins KE, Mugridge KG, Moncada S, Vane JR. The effects of nonsteroid anti-inflammatory drugs on leucocyte migration in carrageen induced inflammation. Eur J Pharmacol 1980;66:81–6.

    PubMed  Google Scholar 

  16. Otterness IG, Larson DL, Lombardino JG. An analysis of piroxicam in rodent models of arthritis. Agents Actions 1982;12:308–12.

    PubMed  Google Scholar 

  17. Reiter MJ, Schwartzmiller DH, Swingle KF,et al. Comparison of anti-inflammatory compounds in the carrageenan induced paw edema model and the reversed passive Arthus model utilizing the same animal. Life Sci 1985;36:1339–46.

    PubMed  Google Scholar 

  18. Perianin A, Roch-Arveiller M, Giroud JP, Hakim J.In vivo effects of indomethacin and flurbiprofen on the locomotion of neutrophils elicited by immune and nonimmune inflammation in the rat. Eur J Pharmacol 1985;106:327–33.

    Google Scholar 

  19. Prockop DJ, Udenfriend SA. A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem 1960;1:228–39.

    PubMed  Google Scholar 

  20. Doornbos R, Prins HJ. On slippage tests III: Two distribution free slippage tests and two tables. Proc Kon Ned Aked Wetensch 1958;A61:438–47.

    Google Scholar 

  21. Fang C, Alexander JW, Mac Millan BG, Austin LS. Failure of topical prostaglandin inhibitors to improve wound healing following deep partial-thickness burns. J Trauma 1983;23:300–4.

    PubMed  Google Scholar 

  22. Diwan PV, Kulkarni DR. Effects of nonsteroidal antiinflammatory agents (NSAIAs) on wound healing. Ind J Exp Biol 1986;24:640–3.

    Google Scholar 

  23. Sato S, Kim T, Arai T, Maruyama S, Tajima M, Utsumi N. Comparison between the effects of dexamethason and indomethacin on bone wound healing. Jpn J Pharmacol 1986;42:71–8.

    PubMed  Google Scholar 

  24. Keller J, Bunger C, Andreassen TT, Bak B, Lucht U. Bone repair inhibited by indomethacin. Effects on bone metabolism and strength of rabbit osteotomies. Acta Orthop Scand 1987;58:379–83.

    PubMed  Google Scholar 

  25. Bacon PA. Nonsteroidal anti-inflammatory drugs and immunologic function: overview of the European experience. Am J Med 1984;77:26–31.

    Google Scholar 

  26. Cronin K, Jackson DS, Dunphy JE. Changing bursting strength and collagen content of the healing colon. Surg Gynecol Obstet 1968;126:747–53.

    PubMed  Google Scholar 

  27. Jiborn H, Ahonen J, Zederfeldt B. Healing of experimental colonic anastomoses III. Collagen metabolism in the colon after left colon resection. Am J Surg 1980;139:398–405.

    PubMed  Google Scholar 

  28. Wojtecka-Lukasik E, Maslinski S. Polymorphonuclear leucocyte collagenase in carrageenin-induced inflammation: the effect of nonsteroidal anti-inflammatory drugs. Int J Tissue Reac 1986;8:321–5.

    Google Scholar 

  29. Wahl LM, Lampel LL. Regulation of human peripheral blood monocyte collagenase by prostaglandins and anti-inflammatory drugs. Cell Immunol 1987; 105:411–22.

    PubMed  Google Scholar 

  30. Brennan SS, Foster ME, Morgan A, Leaper DJ. Prostaglandins in colonic anastomotic healing. Dis Colon Rectum 1984;27:723–5.

    PubMed  Google Scholar 

  31. Cannon RO, Rodriguez ER, Speir E,et al. Effect of ibuprofen on the healing phase of experimental myocardial infarction in the rat. Am J Cardiol 1985;55:1609–13.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, St. Radboud University Hospital, P.O. Box 9101, 6500, HB Nijegen, The Netherlands

    W. J. B. Mastboom M.D., Ph.D., T. Hendriks Ph.D., Ph. van Elteren Ph.D. & H. H. M. de Boer M.D, Ph.D.

  2. Department of Statistical Support, University of Nijmegen, Nijmegen, The Netherlands

    Ph. van Elteren Ph.D.

Authors
  1. W. J. B. Mastboom M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Hendriks Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ph. van Elteren Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. H. M. de Boer M.D, Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Mastboom, W.J.B., Hendriks, T., van Elteren, P. et al. The influence of NSAIDs on experimental intestinal anastomoses. Dis Colon Rectum 34, 236–243 (1991). https://doi.org/10.1007/BF02090163

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02090163

Key words

Search

Navigation