The effect of the antiangiogenic agent paclitaxel on the healing of colonic anastomoses was studied in a rat model. Ninety-six rats underwent end-to-end colonic anastomoses, and healing was evaluated by measuring bursting pressure, hydroxyproline content, and number of newly formed vessels. The rats with end-to-end anastomoses were randomized into control and study groups (n = 48). The rats in the control group were administrated 5 ml physiologic saline intraperitoneally, and those in the study group were given 4.5 mg/kg paclitaxel in 5 ml physiologic saline intraperitoneally. One-half of the rats in both groups were killed on day 4, and the other half were killed on day 7 after surgery with high doses of ether anesthesia. There were no deaths. No detectable improvement in anastomoses bursting pressure was observed in the paclitaxel group on day 4 after surgery. On postoperative day 7, a statistically significant difference was found between the groups (P < 0.05). On day 4 after surgery, there was no statistically significant difference in hydroxyproline levels and vessel density between the two groups (P > 0.05; hydroxyproline: 26.25 versus 16 microg/mg tissue; vessel contents: 110.8 versus 118.2 vessels/x 100 fields for control and study groups, respectively). On postoperative day 7, a significant difference was detected between the two groups (P < 0.0001; hydroxyproline: 40.5 versus 9.6 microg/mg tissue; P < 0.05; vessel contents: 105 versus 85.3 vessels/x 100 fields for control and study groups, respectively). Neovascularization and hydroxyproline levels in rats receiving paclitaxel were significantly reduced on postoperative day 7 (P < 0.05 and P < 0.0001, respectively). These findings suggest that the antiangiogenic efficiency of paclitaxel, and thus, negative impact on wound healing, is more prominent on postoperative day 7. Experimentally, paclitaxel may inhibit and delay healing of colonic anastomoses.
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