Persistent effects of everolimus on strength of experimental wounds in intestine and fascia.
The introduction of mTOR-inhibitors in transplantation surgery has been associated with an increase in wound complications. We have previously reported a massive negative effect of everolimus on anastomotic strength in rat intestine at 7 days postoperatively. Because it is clinically important to know if this effect persists and occurs generally, repair in both intestine and abdominal wall has been investigated over a period of 4 weeks. Wistar rats received a daily dose of 1 or 2 mg/kg everolimus orally, from the operation day onwards. Controls received saline. In each rat a resection of ileum and colon was performed, and end-to-end anastomoses were constructed. On day 7, 14, and 28 the animals were killed and anastomoses and abdominal wall wounds were analyzed, wound strength being the primary parameter. Breaking strength of ileum, colon, and fascia was consistently and significantly reduced in the experimental groups at all time points. Anastomotic bursting pressures followed the same pattern. Loss of strength was accompanied by a decrease in hydroxyproline content after 7 days. Thus, the negative effect of everolimus on wound repair persists for at least 4 weeks after operation in this rodent model. This protracted effect may have clinical consequences and cause surgical morbidity.
Willems
Martine C M
MC
Department of Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. mwillems@flevoziekenhuis.nl
van der Vliet
J Adam
JA
de Man
Ben M
BM
van der Laak
Jeroen A W M
JA
Lomme
Roger M L M
RM
Hendriks
Thijs
T
D034861:Abdominal Wall / Q000502:physiology / Q000601:surgery*; D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005205:Fascia / Q000502:physiology*; D000071938:Fasciotomy; D006909:Hydroxyproline; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000601:surgery*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013314:Stress, Mechanical; D013718:Tensile Strength; D014945:Wound Healing / Q000187:drug effects*
D007166:Immunosuppressive Agents; D003094:Collagen; D000068338:Everolimus; D006909:Hydroxyproline; D020123:Sirolimus