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Abstract
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.
Materials and 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 dissapperance of collagen fibers.
Conclusion. 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.
Keywords
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References
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© 2000 Academic Press. Published by Elsevier Inc. All rights reserved.