Protease inhibitor reduces loss of tensile strength in rat anastomosis with peritonitis.

BACKGROUND

The tensile strength in intestinal anastomoses decreases postoperatively in association with degradation of the extracellular matrix, and these changes would be expected to be more intense in the presence of peritonitis.

METHODS

In this study, we investigated extracellular matrix degradation and tensile strength in a rat model of intestinal anastomosis with peritonitis. In the chemical peritonitis model, peritonitis was induced 24 h earlier with intraperitoneal HCl. A serine protease inhibitor, nafamostat mesilate (NM), was given intraperitoneally to some animals every 12 h from immediately after the operation for 3 days. Immunostaining was performed by the standard streptavidin-biotin-peroxidase method after fibronectin (Fn) and factor XIII antigen retrieval on paraformaldehyde-fixed, paraffin-embedded tissue sections.

RESULTS

In comparison with controls, administration of NM reduced the loss of tensile strength on Day 3 in a dose-dependent manner, and high-dose NM (20/mg/kg) significantly prevented the loss of tensile strength on Day 3 (P < 0. 05). In the control group, degradation of the collagen layer in the anastomosis was associated with disappearance of Fn and factor XIII staining on Day 3. The administration of NM attenuated these changes with intense immunostaining for Fn and factor XIII seen particularly between collagen fibers on both sides of the anastomosis on Day 3. In the chemical peritonitis model, administration of NM also significantly prevented the loss of tensile strength on Day 3 without disappearance of collagen fibers.

CONCLUSIONS

These findings suggest that NM may be clinically useful for preventing intestinal leakage, particularly when anastomoses are performed under protease-activating conditions, such as intestinal edema and inflammation.