title: Doxycycline impacts hernia repair outcomes.
abstract: BACKGROUND
  Incisional hernias occur commonly in up to 20% of all abdominal operations. Incisional hernia formation has been associated with increased levels of matrix metalloproteinases (MMPs), reduced collagen 1, and increased collagen 3 expression. Doxycycline, a nonspecific inhibitor of MMPs, has been shown to beneficially reduce MMP levels in both cancer and aneurysm models. This study evaluates the impact of doxycycline upon MMP expression, collagen subtypes, and hernia repair distraction forces in an animal model of incisional hernia repair.
  
  
  METHODS
  Twenty-four Sprague Dawley rats underwent incisional hernia creation and subsequent repair with polypropylene mesh. Animals were administered doxycycline or saline daily beginning 1 d prior to hernia repair and survived for 1, 2, or 4 wk. Serum and tissue were evaluated for MMP content and collagen subtyping utilizing enzyme-linked immunosorbent assay and Western blot. Tensiometric properties of the native abdominal wall after hernia repair were measured with an Instron Corp. (Canton, MA) mechanical testing system.
  
  
  RESULTS
  There were no differences in control and experimental groups 1 and 2 wk following hernia repair; 4 wk following hernia repair, doxycycline treated animals demonstrated reduced serum MMP-2 and MMP-9 levels, reduced tissue levels of MMP-2, MMP-3, and MMP-9, and increased collagen 1 to 3 ratios. Distraction forces required to disrupt the hernia repair were increased in the doxycycline treated group compared with controls.
  
  
  CONCLUSIONS
  Doxycycline administration is associated with improved hernia repair strength with concomitant reduction of MMP levels with increased collagen 1 deposition. Longer term studies are required to better understand the impact of this treatment.
authors.affiliation: Division of General Surgery, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: Job C
authors.initials: JC
authors.lastname: Tharappel
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Ramineni
authors.forename: Drew
authors.initials: D
authors.lastname: Reynolds
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
authors.forename: J Scott
authors.initials: JS
authors.lastname: Roth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology*; D006555:Hernia, Ventral / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D059685:Herniorrhaphy; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D024042:Collagen Type I; D024061:Collagen Type III; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D004318:Doxycycline
keywords: Collagen; Doxycycline; Hernia; MMP; Matrix metalloproteinase