title: Everolimus-induced loss of wound strength can be prevented by a short postoperative delay in its administration.
abstract: The use of mammalian target of rapamycin inhibitors coincides with an increased incidence of surgical complications. In previous experiments, serious negative effects of postoperative everolimus on anastomotic strength were found. This study aims to investigate if delayed drug administration can prevent loss of wound strength. Ten groups of Wistar rats each received daily oral doses of 1.0 or 2.0 mg/kg everolimus, starting the day of anastomotic construction in both ileum and colon, or 1, 2, 3, or 4 days later. The 11th group received saline. Seven days later, wound strength in anastomoses and in the abdominal wall and wound hydroxyproline levels were measured. Mean wound strength was significantly and dose-dependently reduced if everolimus was started on the day of operation. In ileum and colon, strength was not affected if drug administration was delayed until the third or second day, respectively. In abdominal fascia, this was the case only if everolimus was withheld until day 4. In general, changes in wound hydroxyproline content showed similarities to changes in wound strength. Thus, delaying administration of everolimus for 2-4 days after operation can prevent a serious loss of wound strength, both in the intestine and in the abdominal fascia.
authors.affiliation: Division of Vascular and Transplant Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. mwillems@flevoziekenhuis.nl
authors.forename: Martine C M
authors.initials: MC
authors.lastname: Willems
authors.forename: Thijs
authors.initials: T
authors.lastname: Hendriks
authors.forename: Ben M
authors.initials: BM
authors.lastname: de Man
authors.forename: Roger M L M
authors.initials: RM
authors.lastname: Lomme
authors.forename: J Adam
authors.initials: JA
authors.lastname: van der Vliet
mesh_terms: D000284:Administration, Oral; D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000601:surgery*; D004334:Drug Administration Schedule; D000068338:Everolimus; D006909:Hydroxyproline / Q000378:metabolism; D007082:Ileum / Q000601:surgery*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007813:Laparotomy; D008297:Male; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013718:Tensile Strength; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D003094:Collagen; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D006909:Hydroxyproline; D020123:Sirolimus