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Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model

Syk, Ingvar LU ; Ågren, M S; Adawi, Diya LU and Jeppsson, Bengt LU (2001) In British Journal of Surgery 88(2). p.224-228
Abstract
BACKGROUND: The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. METHODS: Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. RESULTS: Serum BB-1101 levels were increased at 100... (More)
BACKGROUND: The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. METHODS: Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. RESULTS: Serum BB-1101 levels were increased at 100 nmol/l in BB-1101-treated rats. The anastomotic breaking strength was 48 per cent higher (P = 0.02) in BB-1101-treated animals compared with controls on postoperative day 3. Neither collagen accumulation nor infiltration of neutrophils in the anastomotic area was influenced by BB-1101 treatment. Net deposition of new collagen in subcutaneous sponges was unaffected by the BB-1101. CONCLUSION: The enhanced breaking strength of colonic anastomoses during the critical early postoperative phase found after administration of a broad-spectrum MMP inhibitor implies that MMPs might increase the risk of anastomotic dehiscence. Presented in part to the third joint meeting of the European Tissue Repair Society and the Wound Healing Society in Bordeaux, France, 24-28 August 1999, and published in abstract form in Wound Repair Regen 1999; 7: A321 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Surgery
volume
88
issue
2
pages
224 - 228
publisher
John Wiley & Sons
external identifiers
  • pmid:11167872
  • scopus:0035134252
ISSN
1365-2168
DOI
10.1046/j.1365-2168.2001.01649.x
language
English
LU publication?
yes
id
293d237e-4356-4b3f-ab04-e1eed359f996 (old id 1122504)
date added to LUP
2008-07-16 09:31:45
date last changed
2018-10-03 10:46:27
@article{293d237e-4356-4b3f-ab04-e1eed359f996,
  abstract     = {BACKGROUND: The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. METHODS: Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. RESULTS: Serum BB-1101 levels were increased at 100 nmol/l in BB-1101-treated rats. The anastomotic breaking strength was 48 per cent higher (P = 0.02) in BB-1101-treated animals compared with controls on postoperative day 3. Neither collagen accumulation nor infiltration of neutrophils in the anastomotic area was influenced by BB-1101 treatment. Net deposition of new collagen in subcutaneous sponges was unaffected by the BB-1101. CONCLUSION: The enhanced breaking strength of colonic anastomoses during the critical early postoperative phase found after administration of a broad-spectrum MMP inhibitor implies that MMPs might increase the risk of anastomotic dehiscence. Presented in part to the third joint meeting of the European Tissue Repair Society and the Wound Healing Society in Bordeaux, France, 24-28 August 1999, and published in abstract form in Wound Repair Regen 1999; 7: A321},
  author       = {Syk, Ingvar and Ågren, M S and Adawi, Diya and Jeppsson, Bengt},
  issn         = {1365-2168},
  language     = {eng},
  number       = {2},
  pages        = {224--228},
  publisher    = {John Wiley & Sons},
  series       = {British Journal of Surgery},
  title        = {Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model},
  url          = {http://dx.doi.org/10.1046/j.1365-2168.2001.01649.x},
  volume       = {88},
  year         = {2001},
}