title: Microvascular integrity plays an important role for graft survival after experimental skin transplantation.
abstract: BACKGROUND
  Every transplanted organ relies on a reliable and sound vascular system. Therefore, our study focused on the investigation if platelet inhibition alone or combined with mTOR-inhibition has a beneficial effect on the microvascular integrity in allogeneic murine skin grafts.
  
  
  METHODS
  Skin transplantation was performed from fully MHC-mismatched C57BL/6 (H-2b) donors to CBA/J (H-2k) recipient mice. Skin allograft recipients were assigned to several experimental groups and either treated with clopidogrel alone, everolimus alone or a combination of both. Graft survival was evaluated and transplants were harvested after 8 days and analyzed for CD31 and C4d by immunohistochemistry.
  
  
  RESULTS
  Untreated allografts showed a reduced amount of CD31 on postoperative day 8 as well as an increase in C4d compared to isografts. All treated animals showed a significant improvement regarding CD31 [1577.7 ± 200.4 (clopidogrel)/1702.8 ± 151.1 (clopidogrel + everolimus) vs. 479.7 ± 184.2 (control), n = 8, p b 0.05] and C4d [420.9 ± 70.9 (clopidogrel)/324.5 ± 77.3 (clopidogrel + everolimus) vs. 772.4 ± 159.7 (control), n = 8, p b 0.05]. In addition, skin grafts of animals treated with clopidogrel and everolimus survived significantly longer compared to untreated controls [19.2 ± 4.2 d vs. 12.8 ± 2.4 d, n= 10, p b 0.05].
  
  
  CONCLUSIONS
  In this study we could show that clopidogrel alone and in combination with everolimus substantially improved microvascular integrity and resulted in increased survival time of skin grafts.
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Motsch
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heim
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Koch
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Ramsperger-Gleixner
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weyand
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. Electronic address: sensminger@hdz-nrw.de.
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Ensminger
mesh_terms: D064591:Allografts / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage / Q000009:adverse effects; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016038:Skin Transplantation; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D000068338:Everolimus; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: C4d; CD31; Microvessels; Platelets; Skin transplantation