Related Experiment Video
Updated: Jul 18, 2026
Creation of Colonic Anastomosis in Mice
Published on: January 17, 2019
Everolimus interferes with healing of experimental intestinal anastomoses
J Adam van der Vliet1, Martine C M Willems, Ben M de Man
1Department of Surgery, Division of Vascular and Transplant Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands. j.vandervliet@chir.umcn.nl
Background:
Although clinical data suggest its existence, little is known about the effect of rapamycin derivatives on wound repair. This study aims to delineate the influence of the mammalian target of rapamycin inhibitor everolimus on wound healing in the rat intestine.
Methods:
Four groups of 26 male Wistar rats received everolimus in daily oral dosages of 0 (controls), 0.5 (group E-0.5), 1.0 (group E-1), and 3.0 (group E-3) mg/kg every 24 hours, respectively, starting four hours before the operation until killing. After resection of 1-cm segments of colon and ileum, intestinal anastomoses were constructed. The animals were killed at days three or seven after operation. Wound healing was assessed by mechanical (bursting pressure, breaking strength), biochemical (collagen content, gelatinase activity), and histologic parameters.
Results:
No differences between groups were recorded for any of the parameters on day three. On day seven, a dose-dependent reduction in breaking strength (P<0.05) was measured. The largest effects were found in group E-3 in which the breaking strength was reduced by 56% and 73% in colonic and ileal anastomoses, respectively. A similar pattern was observed with the bursting pressure. Loss of strength was accompanied by a reduction in hydroxyproline content and by a lessened collagen deposition in the wound area but not by an increased gelatinase activity. No further histologic abnormalities were found.
Conclusion:
Everolimus causes a massive reduction in anastomotic strength such as normally observed in the proliferative phase of repair. The data suggest this to be caused by an impaired deposition of collagen in the anastomotic area.
Insights
Everolimus significantly reduces intestinal anastomotic strength in rats by impairing collagen deposition during wound repair. This effect, observed on day seven, highlights potential risks of this rapamycin derivative in surgical healing.
Area of Science:
- Gastroenterology
- Pharmacology
- Surgical Research
Background:
- Rapamycin derivatives' impact on wound healing remains unclear.
- Everolimus, a mammalian target of rapamycin inhibitor, is investigated for its effects on intestinal wound repair.
Purpose of the Study:
- To investigate the influence of everolimus on intestinal anastomotic wound healing in a rat model.
- To assess the dose-dependent effects of everolimus on mechanical, biochemical, and histological parameters of wound repair.
Main Methods:
- Wistar rats received daily oral everolimus (0, 0.5, 1.0, 3.0 mg/kg) starting pre-operatively.
- Intestinal anastomoses were created in the colon and ileum.
- Wound healing was evaluated on days three and seven post-operation using mechanical, biochemical, and histological assessments.
Main Results:
- No significant differences were observed on day three.
- On day seven, a dose-dependent reduction in anastomotic breaking strength and bursting pressure was noted.
- Reduced strength correlated with decreased collagen content (hydroxyproline) but not increased gelatinase activity.
Conclusions:
- Everolimus significantly impairs intestinal anastomotic strength, particularly during the proliferative phase of repair.
- The primary mechanism appears to be impaired collagen deposition in the anastomotic site.
- These findings suggest potential complications when using everolimus in patients undergoing intestinal surgery.
