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Introduction: The mTOR-inhibitor everolimus inhibits healing of intestinal anastomoses by interfering with the inflammatory phase of healing and reducing collagen deposition. Aim of this study was to investigate whether the simultaneous administration of everolimus and hGH abolishes the negative effects of everolimus on anastomotic healing.
Methods: 48 male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3mg/kg p.o.; III: everolimus 3mg/kg p.o. + hGH 2,5mg/kg s.c.). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and mechanical, biochemical and histological parameters of intestinal healing were assessed.
Results: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134±19, II: 85±25, III: 114±25 mmHg; p<0,05 I vs. II; p=0,09 I vs. III and II vs. III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14,9±2,5, II: 8,9±3,6, III: 11,9±2,8 µg/mg; p< 0,05 I vs. II/III and II vs. III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10±1, II: 15±3, III: 9±2 n/sqmm; p<0,05 I vs II und II vs. III), while the number of PCNA-positive cells were increased by hGH (I: 28±3, II: 12±3, III: 26±12 /sqmm; p<0,05 I vs. II und II vs. III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.
Conclusion: The inhibitory effects of everolimus on intestinal wound healing can be partially neutralized by simultaneous treatment with human growth hormone. hGH-treatment addresses both the inflammatory phase as well as collagen deposition.