RSS-Feed abonnieren
DOI: 10.1055/s-0029-1241847
© Georg Thieme Verlag KG Stuttgart · New York
The Influence of Enzymes on Adhesive Processes in the Abdominal Cavity
Publikationsverlauf
received May 18, 2009
accepted after revision July 30, 2009
Publikationsdatum:
28. Oktober 2009 (online)

Abstract
Introduction: Intraperitoneal adhesions remain a common problem after abdominal surgery. However, the advent of targeted, specific agents as a directed therapy against inflammatory and neoangiogenesis raises the prospect of a new approach for anti-adhesion strategies.
Methods: 70 adult rats were divided into two groups: an enzyme group (35 rats) and a control group (35 rats). Following laparotomy the visceral peritoneum of the cecum and inner layer the abdominal cavity were abraded. In the enzyme group the preparation Wobenzym (a combination of animal and vegetable proteases plus rutoside) dissolved in 2 ml of sterile 0.9% NaCl was administered to the rats through a gastric probe over a period of 21 days. The control animals received the same quantity of saline without the preparation. On the 1st, 3rd, 7th and 21st postoperative days 8 animals from each group were sacrificed. VEGF, bFGF and laminin were detected in the visceral and parietal peritoneum by immunohistochemistry.
Results: The mean adhesion grades of the enzyme group were significantly lower than in the control group. A comparison of the two groups showed that the expression of VEGF, bFGF and laminin in the enzyme group was lower than in the control group. Moreover, in the enzyme group the concentration of bFGF and laminin peaked on the 7th day, while in the control group the maximum concentrations peaked on day 21.
Conclusions: Our study found that oral poly-enzyme therapy following laparotomy and abrasion of the visceral and parietal peritoneum reduces the extent of postoperative intestinal adhesions. This favorable effect can be explained by the lower levels of angiogenic agents (VEGF, bFGF) and laminin after the administration of hydrolytic enzymes.
Key words
peritoneal adhesions - VEGF - bFGF - laminin - prevention
References
- 1
Carmeliet P.
Angiogenesis in health and disease.
Nature Medicine.
2003;
9
653-660
MissingFormLabel
- 2
Beck DE, Opelka FG, Bailey HR. et al .
Incidence of small-bowel obstruction and adhesiolysis after open colorectal and general
surgery.
Dis Colon Rectum.
1999;
42
241-248
MissingFormLabel
- 3
Bulbuller N, Ilhan YS, Kirkil C. et al .
Can angiotensin converting enzyme inhibitors prevent postoperative adhesions?.
J Surg Res.
2005;
125
94-97
MissingFormLabel
- 4
Cahill RA, Redmond HP.
Cytokine orchestration in post-operative peritoneal adhesion formation.
World J Gastroenterol.
2008;
14
((31))
4861-4866
MissingFormLabel
- 5
Coleman MG, McLain AD, Moran BJ.
Impact of previous surgery on time taken for incision and division of adhesions during
laparotomy.
Dis Colon Rectum.
2000;
43
1297-1299
MissingFormLabel
- 6
Darmas B.
Use of barrier products in the prevention of adhesion formation following surgery.
J Wound Care.
2008;
17
((9))
405-408
MissingFormLabel
- 7
Diegelmann RF, Evans MC.
Wound healing: An overview of acute, fibrotic and delayed healing.
Front Biosci.
2004;
9
283-289
MissingFormLabel
- 8
Ellis LM, Liu W, Fan F.
Role of angiogenesis inhibitors in cancer treatment.
Oncology.
2001;
15
((Suppl 8))
39-46
MissingFormLabel
- 9
Haas TL, Milkiewicz M, Davis SJ. et al .
Matrix metalloproteinase activity is required for activity-induced angiogenesis in
rat skeletal muscle.
Am J Physiol Heart Circ Physiol.
2000;
279
H1540-H1547
MissingFormLabel
- 10
Holland-Cunz S, Boelter AV, Waag KL.
Protective fibrin-sealed plication of the small bowel in recurrent laparotomy.
Pediatr Surg Int.
2003;
19
540-543
MissingFormLabel
- 11
Jaenigen BM, Weis C, Odermatt EK. et al .
The new adhesion prophylaxis membrane A-part(R) – From in vitro testing to first in
vivo results.
J Biomed Mater Res B Appl Biomater.
2008;
6
218-222
MissingFormLabel
- 12
Jendresen MB, Qvist N.
Postoperative peritoneal adhesions.
Ugeskr Laeger.
2008;
170
((42))
3321-3324
MissingFormLabel
- 13
Kawanishi H, Ide K, Yamashita M. et al .
Surgical techniques for prevention of recurrence after total enterolysis in encapsulating
peritoneal sclerosis.
Adv Perit Dial.
2008;
24
51-55
MissingFormLabel
- 14
Kohyama T, Liu X, Wen FQ. et al .
IL-4 and IL-13 induce chemotaxis of human foreskin fibroblasts, but not human fetal
lung fibroblasts.
Inflammation.
2004;
28
33-37
MissingFormLabel
- 15
Kosaka H, Yoshimoto T, Yoshimoto T. et al .
Interferon-gamma is a therapeutic target molecule for prevention of postoperative
adhesion formation.
Nat Med.
2008;
14
437-441
MissingFormLabel
- 16
Manhart N, Akomeah R, Bergmeister H. et al .
Administration of proteolytic enzymes bromelain and trypsin diminishes the number
of CD4+ cells and the interferon-γ response in Peyer's patches and spleen in endotoxemic
balb/c mice.
Cell Immunology.
2002;
215
113-119
MissingFormLabel
- 17
Mirastschijski U, Johannesson K, Jeppsson B. et al .
Effect of a matrix metalloproteinase activity and TNF-alpha converting enzyme inhibitor
on intra-abdominal adhesions.
Eur Surg Res.
2005;
37
68-75
MissingFormLabel
- 18
Molinas CR, Campo R, Dewerchin M. et al .
Role of vascular endothelial growth factor and placental growth factor in basal adhesion
formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after
laparoscopic surgery in transgenic mice.
Fertil Steril.
2003;
80
((Suppl 2))
803-811
MissingFormLabel
- 19
Neurath MF.
Immunotherapy in inflammatory bowel disease: Current concepts and future perspectives.
Arch Immunol Ther Exp Warsz.
2000;
48
81-84
MissingFormLabel
- 20
Pugh CW, Ratcliffe PJ.
Regulation of angiogenesis by hypoxia: Role of the HIF system.
Nat Med.
2003;
9
677-684
MissingFormLabel
- 21
Rout UK, Oommen K, Diamond MP.
Altered expressions of VEGF mRNA splice variants during progression of uterine-peritoneal
adhesions in the rat.
Am J Reprod Immunol.
2000;
43
299-304
MissingFormLabel
- 22
Salmi M, Jalkanen S.
Human leukocyte subpopulations from inflamed gut bind to joint vasculature using distinct
sets of adhesion molecules.
J Immunol.
2001;
166
4650-4657
MissingFormLabel
- 23
Takahashi I, Kiyono H.
Gut as the largest immunologic tissue.
JPEN.
1999;
23
S7-S12
MissingFormLabel
- 24
Uguralp S, Akin M, Karabulut A. et al .
Reduction of peritoneal adhesions by sustained and local administration of epidermal
growth factor.
Pediatr Surg Int.
2008;
24
191-197
MissingFormLabel
- 25
Van Der Krabben AA, Dijkstra FR, Nieuwenhuijzen M. et al .
Morbidity and mortality of inadvertent enterotomy during adhesiotomy.
Br J Surg.
2000;
87
467-471
MissingFormLabel
- 26
Wagoner LE, Merrill W, Jacobs J. et al .
Angiogenesis protein therapy with human fibroblast growth factor (FGF-1): Results
of a phase I open label.
Circulation.
2007;
116
443-446
MissingFormLabel
- 27
Williams RS, Rossi AM, Chegini N. et al .
Effect of transforming growth factor beta on postoperative adhesion formation and
intact peritoneum.
J Surg Res.
1992;
52
65-70
MissingFormLabel
- 28
Williams SG, Buscarini M, Stein JP.
Molecular markers for diagnosis, staging, and prognosis of bladder Cancer.
Oncology.
2001;
15
1461-1484
MissingFormLabel
- 29
Xu W, Niu A, Li Zh. et al .
Effect of pingyangmycin emulsion on the microenvironment of infantile proliferating
capillary hemangioma.
World J Pediatr.
2006;
3
217-222
MissingFormLabel
- 30
Xu X, Rivkind A, Pappo O. et al .
Role of mast cells and myofibroblasts in human peritoneal adhesion formation.
Ann Surg.
2002;
236
593-601
MissingFormLabel
- 31
Zhenchevskii RA, Gumilevskaia EM.
Pathogenesis of chronic productive peritonitis.
Vestn Khir Im I I Grek..
1986;
136
((5))
24-28
MissingFormLabel
Correspondence
Prof. Sergey Victorovich Minaev
Stavropol State Medical Academy, Pediatric Surgery
70/1–15 Shpakovskaya St. 355037 Stavropol
Russian Federation
Telefon: +78652607653
Fax: +78652357870
eMail: sminaev@yandex.ru