title: Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion.
abstract: BACKGROUND
  Nitric oxide (NO) participates in the regulation of hemodynamic and microcirculatory changes in intestinal ischemia and reperfusion (I/R). However, the nature of the involvement of an inducible NO release has been controversial. This study evaluates the impact of an inducible NO synthase inhibitor, aminoguanidine, used as a treatment in a rat intestinal I/R model.
  
  
  METHODS
  We investigated the hemodynamics by measuring the mean arterial pressure (MAP), and the microcirculatory responses of the intestine and liver to systemically administered aminoguanidine by use of laser-Doppler flowmetry (LDF), in vivo microscopy, and flow cytometry.
  
  
  RESULTS
  During the 30-min ischemia of the selected 20-cm ileal segment, no MAP change was noted. At reperfusion, a marked decrease of MAP was noted and the lowest levels were noted 3 hours after reperfusion (67 +/- 4% vs. 99 +/- 5% in sham-operated control animals). A marked decrease in liver perfusion as measured by LDF was noted 1 hour after reperfusion and remained low at 5 hours (72 +/- 4% vs. 97 +/- 3% in sham-operated control animals). A marked decrease in intestine perfusion was noted by using LDF 1 hour after reperfusion and remained low at 5 hours (43 +/- 3% vs. 92 +/- 4% in sham-operated control animals). The flow velocity of the postcapillary venules of the intestine was markedly decreased (1.01 +/- 0.62 vs. 2.67 +/- 0.34 mm/s in sham-operated control animals) at 5 hours after reperfusion. The flow velocity of the postsinusoidal venules of the liver was also markedly decreased (1.01 +/- 0.62% vs. 2.67 +/- 0.34% in sham-operated control animals). Leukocyte-endothelial interaction (adhesion) was increased in the postcapillary venules of the intestine (54 +/- 12 vs. 6 +/- 4/microm2 in sham-operated control animals) and in the postsinusoidal venules of the liver (32 +/- 8 vs. 2 +/- 2/microm2 in sham-operated control animals). Concomitantly, the granulocyte count was increased (9.1 +/- 0.6 vs. 2.1 +/- 0.3% of total circulating leukocytes in sham-operated control animals), with an increase of CD 11b expression. Aminoguanidine administration (1 mg/kg) 0.5 hour before ischemia and 1 hour after reperfusion significantly increased MAP, increased intestine and liver perfusion, decreased adhesion, and decreased circulating granulocytes and CD 11b expression.
  
  
  CONCLUSIONS
  Inhibition of an inducible NO release by aminoguanidine in intestinal I/R can attenuate hemodynamic and microcirculatory derangement.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
authors.forename: C C
authors.initials: CC
authors.lastname: Lo
authors.forename: J C
authors.initials: JC
authors.lastname: Chen
authors.forename: H M
authors.initials: HM
authors.lastname: Chen
authors.forename: M H
authors.initials: MH
authors.lastname: Shyr
authors.forename: Y T
authors.initials: YT
authors.lastname: Lau
authors.forename: J N
authors.initials: JN
authors.lastname: Lin
authors.forename: M F
authors.initials: MF
authors.lastname: Chen
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006098:Granulocytes / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007422:Intestines / Q000098:blood supply*; D017078:Laser-Doppler Flowmetry; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply*; D016177:Macrophage-1 Antigen / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014699:Venules / Q000187:drug effects
chemical_list: D006146:Guanidines; D016177:Macrophage-1 Antigen; D019001:Nitric Oxide Synthase; C004479:pimagedine