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

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.

• Authors: I H J T de Hingh, M A Siemonsma, B M de Man, R M L M Lomme, T Hendriks
• Journal: International journal of colorectal disease (Int J Colorectal Dis) Vol. 17 Issue 5 Pg. 348-54 (Sep 2002) ISSN: 0179-1958 [Print] Germany
• PMID: 12172929 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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