Introduction: The mTOR-inhibitor everolimus is a derivate of sirolimus. It is known, that immunosuppressive drugs impair the healing of the skin both clinical and in an animal model [1,2]. The most distinctive wound complications were noticed under medication with sirolimus [2]. Aim of this experimental research is to investigate the effects of everolimus on the healing of experimental colonic anastomoses.
Material and Method: Three groups (n=10/group) of male Sprague-Dawley-rats received a distal colonic anastomosis and afterwards daily treatment with either vehicle [P] or everolimus in two different dosages (1.0mg/kg BW [E1]; 3.0mg/kg BW [E2]). After 7 days the rats were killed, the anastomosis was resected in toto and the “bursting pressure” (mmHg) was measured. A basic histological staining followed (HE and Azan), as well as the quantitative measurement of hydroxyprolin as a parameter for the collagen content of the tissue (µg/mg dry-weight [DW]) and PCNA as a marker for the cell proliferation (Quantimet: positive cells/sqmm).
Results: The anastomotic “bursting pressure” was significantly decreased by the everolimus treatment in both dosages (117±25 vs. 142±17mmHg; p=0.02 E1 vs. P and 108±30 vs. 142±17mmHg; p=0.006 E2 vs. P). The anastomotic hydroxyprolin-content was reduced only by the high everolimus dosage (6.20 vs. 9.77µg/mg DW; p=0.007 E2 vs. P). The number of PCNA-positive cell nuclei also was significantly reduced by everolimus (P: 11091±1976/sqmm, E1: 8067±1127/sqmm, E2: 6352±1271/sqmm). The Azan-staining revealed more unordered collagen fibres under everolimus treatment.
Conclusion: Everolimus impairs the intestinal wound healing by inhibition of the cell proliferation, which increases with rising dosages. On the other hand, the anastomotic hydroxyprolin content was reduced only by the high dosage of everolimus. Corrensponding to these data, the anastomotic “bursting pressure” is significantly reduced under treatment with everolimus.References:1. Schaffer et al. 2005, J Invest Surg. 18: 71-79. 2. Dean et al. 2004, Transplantation 77:1555-1561;