title: Prophylactic amifostine prevents a pathologic vascular response in a murine model of expander-based breast reconstruction.
abstract: BACKGROUND
  Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction.
  
  
  METHODS
  30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis.
  
  
  RESULTS
  Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339).
  
  
  CONCLUSIONS
  Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Polyatskaya
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Nelson
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Rodriguez
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Zheutlin
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Department of Surgery, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Felice
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Donneys
authors.affiliation: Craniofacial Research Laboratory, Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: sbuchman@med.umich.edu.
authors.forename: S R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D004999:Amifostine / Q000008:administration & dosage*; D000792:Angiography; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000532:radiotherapy* / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D021621:Imaging, Three-Dimensional; D008297:Male; D016462:Mammaplasty / Q000379:methods*; D008323:Mammary Arteries / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D009374:Neoplasms, Experimental; D011833:Radiation Injuries, Experimental / Q000175:diagnosis / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015625:Tissue Expansion Devices
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine
keywords: Amifostine; Breast cancer; Expander-based reconstruction; Immediate breast reconstruction; Radiotherapy; Vascularity