Doxycycline improves wound strength after intestinal anastomosis in the rat

Background. 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. The aim of this study was to examine whether doxycycline, a drug known to inhibit 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 doxycycline (orally or subcutaneously) in a dose of 10 mg/day or with saline only. Rats were killed 1, 3, or 5 days after operation, and anastomotic bursting pressure and breaking strength were measured. At day 3, anastomotic hydroxyproline levels were measured, MMP (gelatinase) activity was analyzed by gelatin zymography, and anastomotic histology was examined. Results. Doxycycline enhanced wound strength, but only at day 3, when it was at its lowest. Subcutaneous administration of 10 mg/day increased median colonic and ileal breaking strength by 27% (P =.0019) and 104% (P =.0376), respectively. Colonic bursting pressure was increased by 93% (P =.0002). Wound histology was similar in experimental and control groups. Conclusions. Administration of doxycycline enhances anastomotic strength and should be investigated further as a means to preserve anastomotic integrity. (Surgery 2003;133:268-76.)