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


CONCLUSIONS
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
Syk
I
I
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden. ingvar.syk@telia.com
Agren
M S
MS
Adawi
D
D
Jeppsson
B
B
D000714:Anastomosis, Surgical; D000818:Animals; D001593:Benzyl Compounds; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000601:surgery*; D003907:Dexamethasone / Q000097:blood / Q000627:therapeutic use*; D004338:Drug Combinations; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010431:Pentoxifylline / Q000097:blood / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates; D013529:Surgical Wound Dehiscence / Q000503:physiopathology / Q000517:prevention & control*
C101468:BB 1101; D001593:Benzyl Compounds; D004338:Drug Combinations; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013386:Succinates; D003907:Dexamethasone; D003094:Collagen; D006909:Hydroxyproline; D010431:Pentoxifylline