The matrix metalloproteinase inhibitor BB-94 improves the strength of intestinal anastomoses in the rat.
OBJECTIVE
The strength of intestinal anastomoses is relatively low in the first days after operation, possibly as a result of localized degradation of the supporting matrix by enzymes from the matrix metalloproteinase (MMP) family. This study examined whether BB-94, a broad spectrum inhibitor of MMP activity, could enhance anastomotic strength.


METHODS
Male Wistar rats received anastomoses in both ileum and colon. From the day before operation onwards, animals were treated daily with BB-94 intraperitoneally at a dose of 30 mg/kg or with saline only. Rats were killed 1, 3, or 7 days after operation, and anastomotic bursting pressure and breaking strength were measured. On day 3 anastomotic hydroxyproline levels were measured, and MMP (gelatinase) activity was analyzed by gelatin zymography.


RESULTS
BB-94 strongly enhanced wound strength, but only on day 3, when it was at its lowest. Daily administration increased median colonic and ileal breaking strength by 27% and 108%, respectively; colonic and ileal bursting pressure were increased by 54% and 58%, respectively. MMP activities were significantly lowered in anastomotic extracts from the rats treated with BB-94.


CONCLUSIONS
Administration of BB-94 enhances anastomotic strength. Specific inhibition of MMP activity should be investigated further as a means to preserve anastomotic integrity.
de Hingh
I H J T
IH
Department of Surgery, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
Siemonsma
M A
MA
de Man
B M
BM
Lomme
R M L M
RM
Hendriks
T
T
D000714:Anastomosis, Surgical; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology* / Q000601:surgery*; D006909:Hydroxyproline / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology* / Q000601:surgery*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000187:drug effects*; D023421:Models, Animal; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011184:Postoperative Period; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D020782:Matrix Metalloproteinases; D006909:Hydroxyproline