title: N-acetylcysteine attenuates leukocytic inflammation and microvascular perfusion failure in critically ischemic random pattern flaps.
abstract: BACKGROUND
  Microcirculatory dysfunction causes ischemia resulting in tissue necrosis. N-acetylcysteine (NAC) has been shown capable of protecting tissue from ischemic necrosis. However, the mechanism of action of NAC is yet not fully understood.
  
  
  OBJECTIVE
  Herein, we studied whether NAC is capable of attenuating microvascular perfusion failure in critically ischemic musculo-cutaneous tissue.
  
  
  METHODS
  A laterally based skin flap was elevated in the dorsum of C57BL/6 mice and fixed into a dorsal skinfold chamber. Arteriolar perfusion, functional capillary density, leukocytic inflammation, apoptotic cell death, and non-perfused tissue area were repetitively analyzed over 10 days by intravital fluorescence microscopy. Treatment with either 100mg/kg NAC or saline (control) was started 30 min before surgery and was continued until day 10 after flap elevation.
  
  
  RESULTS
  Surgery induced leukocytic inflammation, microvascular perfusion failure, apoptosis, and tissue perfusion failure. NAC was capable of significantly attenuating the area of non-perfused tissue. This was associated by a marked arteriolar dilation and an increased capillary perfusion. NAC further reduced the ischemia-associated leukocytic response and significantly attenuated apoptotic cell death in all areas of the flap.
  
  
  CONCLUSIONS
  NAC is effective to attenuate leukocytic inflammation and microvascular perfusion failure in critically ischemic tissue. Thus, NAC treatment may represent a promising approach to improve the outcome of ischemically endangered flap tissue.
authors.affiliation: Institute for Clinical and Experimental Surgery, University of Saarland, 66421-Homburg/Saar, Germany. annick.baechle@uniklinikum-saarland.de
authors.forename: A C
authors.initials: AC
authors.lastname: Bächle
authors.forename: P
authors.initials: P
authors.lastname: Mörsdorf
authors.forename: F
authors.initials: F
authors.lastname: Rezaeian
authors.forename: M F
authors.initials: MF
authors.lastname: Ong
authors.forename: Y
authors.initials: Y
authors.lastname: Harder
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D062109:Dermatologic Surgical Procedures; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis / Q000473:pathology / Q000517:prevention & control; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000111:Acetylcysteine