title: Development of 'no-reflow' phenomenon in ischemia/reperfusion injury: failure of active vasomotility and not simply passive vasoconstriction.
abstract: OBJECTIVE
  Local blood flow failure (no-reflow phenomenon) during ischemia/reperfusion (I/R) injury may be mediated by interstitial edema formation (passive vasoconstriction) and/or microvascular spasm (active vasoconstriction). The development of the no-reflow phenomenon in the rabbit hind limb I/R model and the influence of treatment with L-arginine and/or antioxidative vitamins were investigated.
  
  
  METHODS
  Untreated rabbits were compared with those treated with L-arginine (4 mg/kg/min) or antioxidative vitamins (0.4 ml/kg) alone or in combination during hind limb I/R (2.5/2 h). Interstitial edema formation and microvessel diameter alterations were measured morphometrically. Capillary blood perfusion was measured continuously with laser Doppler flowmetry.
  
  
  RESULTS
  I/R injury was expressed by interstitial edema formation (interstitial space increase by 80%), microvascular constriction (microvessel cross-sectional area decrease by 30%), and development of no-reflow phenomenon (blood flow reduction by 60%). Treatment with antioxidative vitamins alone or L-arginine alone reduced interstitial edema by 22 and 31%, consequently, while combined L-arginine/antioxidative vitamin treatment showed a more pronounced edema reduction by 40%. Treatment with only antioxidative vitamins failed to influence the development of no-reflow, although interstitial edema formation was reduced. L-Arginine treatment alone or in combination with antioxidative vitamins prevented microvascular constriction and preserved blood flow after reperfusion without development of no-reflow despite still apparent interstitial edema.
  
  
  CONCLUSIONS
  Affections of active vasomotility and not merely passive changes of external pressure (i.e., interstitial edema formation) should be considered important in the development of microvascular constriction during 'no-reflow' phenomenon.
authors.affiliation: Department of Vascular Surgery, University of Vienna Medical School, AKH, Vienna, Austria. josif.nanobachvili@akh-wien.ac.at
authors.forename: J
authors.initials: J
authors.lastname: Nanobashvili
authors.forename: C
authors.initials: C
authors.lastname: Neumayer
authors.forename: A
authors.initials: A
authors.lastname: Fuegl
authors.forename: R
authors.initials: R
authors.lastname: Blumer
authors.forename: M
authors.initials: M
authors.lastname: Prager
authors.forename: E
authors.initials: E
authors.lastname: Sporn
authors.forename: P
authors.initials: P
authors.lastname: Polterauer
authors.forename: T
authors.initials: T
authors.lastname: Malinski
authors.forename: I
authors.initials: I
authors.lastname: Huk
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001808:Blood Vessels / Q000473:pathology; D002196:Capillaries / Q000503:physiopathology; D004338:Drug Combinations; D004487:Edema / Q000209:etiology / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D014661:Vasoconstriction; D014666:Vasomotor System / Q000503:physiopathology*; D014815:Vitamins / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D014815:Vitamins; D001120:Arginine