title: Pretreatment of pericardial patches with antibiotics does not alter patch healing in vivo.
abstract: BACKGROUND
  Pretreatment with antibiotics is commonly performed before surgical implantation of prosthetic materials. We previously showed that pericardial patches are infiltrated by macrophages and arterial stem cells after implantation into an artery. We hypothesized that antibiotic pretreatment would diminish the number of cells infiltrating into the patch, potentially affecting early neointimal formation.
  
  
  METHODS
  Bovine pericardial patches were pretreated with saline, bacitracin (500 U/mL), or cephalexin (10 mg/mL) for 30 minutes before implantation into the Wistar rat infrarenal aorta. Patches were retrieved on day 7 or day 30 and analyzed for histology and cell infiltration. Markers of proliferation, apoptosis, vascular cell identity, and M1 and M2 macrophage subtypes were examined using immunofluorescence and immunohistochemistry. Extracted proteins were analyzed by Western blot.
  
  
  RESULTS
  At day 7, pericardial patches pretreated with bacitracin or cephalexin showed similar amounts of neointimal thickening (P = .55) and cellular infiltration (P = .42) compared with control patches. Patches pretreated with antibiotics showed similar proliferation (P = .09) and apoptosis (P = .84) as control patches. The cell composition of the neointima in pretreated patches was similar to control patches, with a thin endothelial layer overlying a thin layer of smooth muscle cells (P = .45), and containing similar numbers of CD34-positive (P = .26) and vascular endothelial growth factor receptor 2-positive (P = .31) cells. Interestingly, within the body of the patch, there were fewer macrophages (P = .0003) and a trend towards fewer endothelial progenitor cells (P = .051). No M1 macrophages were found in or around any of the patches. M2 macrophages were present around the patches, and there was no difference in numbers of M2 macrophages surrounding control patches and patches pretreated with antibiotics (P = .24). There was no difference in neointimal thickness at day 30 between control patches and patches pretreated with antibiotics (P = .52).
  
  
  CONCLUSIONS
  Pretreatment of bovine pericardial patches with the antibiotics bacitracin or cephalexin has no detrimental effect on early patch healing, with similar neointimal thickness, cellular infiltration, and numbers of M2 macrophages compared with control patches. These results suggest that the host vessel response to patch angioplasty using pericardial patches is adaptive remodeling (eg, arterial healing).
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn; Basic Medical College of Zhengzhou University, Henan, China; Department of Vascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China.
authors.forename: Hualong
authors.initials: H
authors.lastname: Bai
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn.
authors.forename: Go
authors.initials: G
authors.lastname: Kuwahara
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn.
authors.forename: Mo
authors.initials: M
authors.lastname: Wang
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn.
authors.forename: Kirstyn E
authors.initials: KE
authors.lastname: Brownson
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn.
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Foster
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn; Department of Surgery, Veterans Affairs Connecticut Healthcare Systems, West Haven, Conn.
authors.forename: Kota
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Basic Medical College of Zhengzhou University, Henan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Vascular Biology and Therapeutics Program and the Department of Surgery, Yale University School of Medicine, New Haven, Conn; Department of Surgery, Veterans Affairs Connecticut Healthcare Systems, West Haven, Conn. Electronic address: alan.dardik@yale.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D017209:Apoptosis / Q000187:drug effects; D001414:Bacitracin / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002506:Cephalexin / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D058426:Neointima; D010496:Pericardium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D017208:Rats, Wistar; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D001414:Bacitracin; D002506:Cephalexin