Top

Surgical Endoscopy

Published in:

01-10-2007

A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation

Authors: S. G. Prushik, C. B. Aarons, R. Matteotti, K. L. Reed, A. C. Gower, S. E. Leeman, A. F. Stucchi, J. M. Becker

Published in: Surgical Endoscopy | Issue 10/2007

Abstract

Background

Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA.

Methods

Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively.

Results

At laparoscopy, 79% ± 3% of the buttons formed adhesions. In the saline-administered control animals, 42% ± 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% ± 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 ± 2.1 U/ml vs 1.2 ± 0.54 U/ml).

Conclusions

When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation.

Becker JM, Dayton MT, Fazio VW, Beck DE, Stryker SJ, Wexner SD, Wolff BG, Roberts PL, Smith LE, Sweeney SA, Moore M (1996) Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. J Am Coll Surg 183(4): 297–306PubMed

Menzies D, Ellis H (1990) Intestinal obstruction from adhesions: how big is the problem? Ann R Coll Surg Engl 72(1): 60–63PubMed

Punch MR, Roth RS (1993) Adhesions and chronic pain: an overview of pain and a discussion of adhesions and pelvic pain. Prog Clin Biol Res 381: 101–120PubMed

Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS, Menzies D, McGuire A, Lower AM, Hawthorn RJ, O'Brien F, Buchan S, Crowe AM (1999) Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet 353(9163): 1476–1480PubMedCrossRef

Ray NF, Denton WG, Thamer M, Henderson SC, Perry S (1998) Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994. J Am Coll Surg 186(1): 1–9PubMedCrossRef

Pickleman J (1997) Small bowel obstruction. In: Zinner MJ (ed) Maingot’s abdominal operations. Prentice-Hall, London, pp 1159–1172

Welch P (1990) Adhesions. In: Welch (ed) Bowel obstruction. Saunders, Philadelphia, pp 154–165

Beck DE, Opelka FG, Bailey HR, Rauh SM, Pashos CL (1999) Incidence of small-bowel obstruction and adhesiolysis after open colorectal and general surgery. Dis Colon Rectum 42(2): 241–248PubMedCrossRef

Luijendijk RW, Hop WC, van den Tol MP, de Lange DC, Braaksma MM, JN IJ, Boelhouwer RU, de Vries BC, Salu MK, Wereldsma JC, Bruijninckx CM, Jeekel J (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343(6): 392–398PubMedCrossRef

10.

Fevang BT, Fevang J, Lie SA, Soreide O, Svanes K, Viste A (2004) Long-term prognosis after operation for adhesive small bowel obstruction. Ann Surg 240(2): 193–201PubMedCrossRef

11.

Duepree HJ, Senagore AJ, Delaney CP, Fazio VW (2003) Does means of access affect the incidence of small bowel obstruction and ventral hernia after bowel resection? Laparoscopy versus laparotomy. J Am Coll Surg 197(2): 177–181PubMedCrossRef

12.

Chopra R, McVay C, Phillips E, Khalili TM (2003) Laparoscopic lysis of adhesions. Am Surg 69(11): 966–968PubMed

13.

Franklin ME Jr, Dorman JP, Pharand D (1994) Laparoscopic surgery in acute small bowel obstruction. Surg Laparosc Endosc 4(4): 289–296PubMed

14.

Gutt CN, Oniu T, Schemmer P, Mehrabi A, Buchler MW (2004) Fewer adhesions induced by laparoscopic surgery? Surg Endosc 18(6): 898–906PubMedCrossRef

15.

Ibrahim IM, Wolodiger F, Sussman B, Kahn M, Silvestri F, Sabar A (1996) Laparoscopic management of acute small-bowel obstruction. Surg Endosc 10(10): 1012–1014, discussion 1014–1015PubMedCrossRef

16.

Liauw JJ, Cheah WK (2005) Laparoscopic management of acute small bowel obstruction. Asian J Surg 28(3): 185–188PubMedCrossRef

17.

diZeraga GS, Rogers KE (1992) The peritoneum. Springer-Verlag, New York

18.

diZerega GS, Campeau JD (2001) Peritoneal repair and post-surgical adhesion formation. Hum Reprod Update 7(6): 547–555PubMedCrossRef

19.

Thompson J (1998) Pathogenesis and prevention of adhesion formation. Dig Surg 15(2): 153–157PubMedCrossRef

20.

Thompson J (2000) Peritoneal fibrinolysis and adhesion formation. In: diZeraga GS (ed) Peritoneal surgery. Springer-Verlag, New York pp 133–142

21.

Holmdahl L (1997) The role of fibrinolysis in adhesion formation. Eur J Surg Suppl 577: 24–31PubMed

22.

Holmdahl L, Falkenberg M, Ivarsson ML, Risberg B (1997) Plasminogen activators and inhibitors in peritoneal tissue. APMIS 105(1): 25–30PubMedCrossRef

23.

Holmdahl L, Eriksson E, Eriksson BI, Risberg B (1998) Depression of peritoneal fibrinolysis during operation is a local response to trauma. Surgery 123(5): 539–544PubMedCrossRef

24.

Holzer P, Holzer-Petsche U (1997) Tachykinins in the gut: Part II. Roles in neural excitation, secretion, and inflammation. Pharmacol Ther 73(3): 219–263PubMedCrossRef

25.

Hokfelt T, Pernow B, Wahren J (2001) Substance P: a pioneer amongst neuropeptides. J Intern Med 249(1): 27–40PubMedCrossRef

26.

Mantyh CR, Maggio JE, Mantyh PW, Vigna SR, Pappas TN (1996) Increased substance P receptor expression by blood vessels and lymphoid aggregates in Clostridium difficile–induced pseudomembranous colitis. Dig Dis Sci 41(3): 614–620PubMedCrossRef

27.

Bhatia M, Saluja AK, Hofbauer B, Frossard JL, Lee HS, Castagliuolo I, Wang CC, Gerard N, Pothoulakis C, Steer ML (1998) Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. Proc Natl Acad Sci USA 95(8): 4760–4765PubMedCrossRef

28.

Katayama I, Nishioka K (1997) Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis. J Dermatol Sci 15(3): 201–206PubMedCrossRef

29.

Schaffer M, Beiter T, Becker HD, Hunt TK (1998) Neuropeptides: mediators of inflammation and tissue repair? Arch Surg 133(10): 1107–1116PubMedCrossRef

30.

Azzolina A, Bongiovanni A, Lampiasi N (2003) Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochim Biophys Acta 1643(1–3): 75–83PubMed

31.

Fan TP, Hu DE, Guard S, Gresham GA, Watling KJ (1993) Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition by NK1 or interleukin-1 receptor antagonists. Br J Pharmacol 110(1): 43–49PubMed

32.

Ziche M, Morbidelli L, Pacini M, Dolara P, Maggi CA (1990) NK1-receptors mediate the proliferative response of human fibroblasts to tachykinins. Br J Pharmacol 100(1): 11–14PubMed

33.

Lai JP, Douglas SD, Ho WZ (1998) Human lymphocytes express substance P and its receptor. J Neuroimmunol 86(1): 80–86PubMedCrossRef

34.

Ho WZ, Lai JP, Zhu XH, Uvaydova M, Douglas SD (1997) Human monocytes and macrophages express substance P and neurokinin-1 receptor. J Immunol 159(11): 5654–5660PubMed

35.

Metwali A, Blum AM, Ferraris L, Klein JS, Fiocchi C, Weinstock JV (1994) Eosinophils within the healthy or inflamed human intestine produce substance P and vasoactive intestinal peptide. J Neuroimmunol 52(1): 69–78PubMedCrossRef

36.

Sanfilippo JS, Williams RS, Yussman MA, Cook CL, Bissonnette F (1992) Substance P in peritoneal fluid. Am J Obstet Gynecol 166(1 Pt 1): 155–159PubMed

37.

Sulaiman H, Gabella G, Davis MC, Mutsaers SE, Boulos P, Laurent GJ, Herrick SE (2001) Presence and distribution of sensory nerve fibers in human peritoneal adhesions. Ann Surg 234(2): 256–261PubMedCrossRef

38.

Boland GM, Weigel RJ (2006) Formation and prevention of postoperative abdominal adhesions. J Surg Res 132(1): 3–12PubMedCrossRef

39.

Reed KL, Fruin AB, Gower AC, Stucchi AF, Leeman SE, Becker JM (2004) A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity. Proc Natl Acad Sci USA 101(24): 9115–9120PubMedCrossRef

40.

Khaitan E, Scholz S, Richards WO (2002) Laparoscopic adhesiolysis and placement of Seprafilm: a new technique and novel approach to patients with intractable abdominal pain. J Laparoendosc Adv Surg Tech A 12(4): 241–247PubMedCrossRef

41.

Khaitan L, Scholz S, Houston HL, Richards WO (2003) Results after laparoscopic lysis of adhesions and placement of seprafilm for intractable abdominal pain. Surg Endosc 17(2): 247–253PubMedCrossRef

42.

Stucchi AF, Shebani KO, Leeman SE, Wang CC, Reed KL, Fruin AB, Gower AC, McClung JP, Andry CD, O'Brien MJ, Pothoulakis C, Becker JM (2003) A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus. Am J Physiol Gastrointest Liver Physiol 285(6): G1259–1267PubMed

43.

Reed KL, Fruin AB, Bishop-Bartolomei KK, Gower AC, Nicolaou M, Stucchi AF, Leeman SE, Becker JM (2002) Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J Surg Res 108(1): 165–172PubMedCrossRef

44.

Ho WZ, Kaufman D, Uvaydova M, Douglas SD (1996) Substance P augments interleukin-10 and tumor necrosis factor-alpha release by human cord blood monocytes and macrophages. J Neuroimmunol 71(1–2): 73–80PubMedCrossRef

45.

Carolan EJ, Casale TB (1993) Effects of neuropeptides on neutrophil migration through noncellular and endothelial barriers. J Allergy Clin Immunol 92(4): 589–598PubMedCrossRef

46.

Frode-Saleh TS, Calixto JB, Medeiros YS (1999) Analysis of the inflammatory response induced by substance P in the mouse pleural cavity. Peptides 20(2): 259–265PubMedCrossRef

Title: A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation
Authors: S. G. Prushik
C. B. Aarons
R. Matteotti
K. L. Reed
A. C. Gower
S. E. Leeman
A. F. Stucchi
J. M. Becker
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: Surgical Endoscopy / Issue 10/2007
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI: https://doi.org/10.1007/s00464-007-9248-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 10/2007

Effect of reactive oxygen species scavengers, antiinflammatory drugs, and calcium-channel blockers on carbon dioxide pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model

Perceptual and instrumental impacts of robotic laparoscopy on surgical performance

Using an image-guided navigation system for localization of small pulmonary nodules before thoracoscopic surgery

Gastrointestinal stromal tumors (GIST) and laparoscopic resection

The Impact of Uncomplicated and Complicated Diverticulitis on Laparoscopic Surgery Conversion Rates and Patient Outcomes

A new method for intrathoracic anastomosis in laparoscopic esophagectomy