Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion

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/μm² in shamoperated control animals) and in the postsinusoidal venules of the liver (32 ± 8 vs. 2 ± 2/μm² 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. Conclusion: Inhibition of an inducible NO release by aminoguanidine in intestinal I/R can attenuate hemodynamic and microcirculatory derangement.