The matrix metalloproteinase inhibitor BB-94 improves the strength of intestinal anastomoses in the rat

Int J Colorectal Dis. 2002 Sep;17(5):348-54. doi: 10.1007/s00384-002-0418-3. Epub 2002 Jun 21.

Abstract

Background and aims: 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.

Materials and 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.

Conclusion: Administration of BB-94 enhances anastomotic strength. Specific inhibition of MMP activity should be investigated further as a means to preserve anastomotic integrity.

Publication types

  • Comparative Study

MeSH terms

  • Anastomosis, Surgical
  • Animals
  • Colon / drug effects
  • Colon / physiology*
  • Colon / surgery*
  • Hydroxyproline / drug effects
  • Ileum / drug effects
  • Ileum / physiology*
  • Ileum / surgery*
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / drug effects*
  • Models, Animal
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology*
  • Postoperative Period
  • Protease Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar
  • Thiophenes / pharmacology*
  • Time Factors
  • Treatment Outcome

Substances

  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Thiophenes
  • Phenylalanine
  • batimastat
  • Matrix Metalloproteinases
  • Hydroxyproline