Cc. Lo et al., Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion, J TRAUMA, 47(6), 1999, pp. 1108-1113
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 mod
el.
Methods: We investigated the hemodynamics by measuring the mean arterial pr
essure (MAP), and the microcirculatory responses of the intestine and liver
to systemically administered aminoguanidine by use of laser-Doppler flowme
try (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 a
nd the lowest levels were noted 3 hours after reperfusion (67 +/- 4% vs. 99
+/- 5% in sham-operated control animals). A marked decrease in liver perfu
sion as measured by LDF was noted I hour after reperfusion and remained low
at 5 hours (72 +/- 4% vs. 97 +/- 3% in sham-operated control animals), A m
arked decrease in intestine perfusion was noted by using LDF 1 hour after r
eperfusion and remained low at 5 hours (43 +/- 3% vs. 92 +/- 4% in sham-ope
rated control animals). The flow velocity of the postcapillary venules of t
he intestine was markedly decreased (1.01 +/- 0.62 vs. 2.67 +/- 0.34 mm/s i
n sham-operated control animals) at 5 hours after reperfusion, The flow vel
ocity of the postsinusoidal venules of the liver was also markedly decrease
d (1.01 +/- 0.62% vs. 2.67 +/- 0.34% in sham-operated control animals). Leu
kocyte-endothelial interaction (adhesion) was increased in the postcapillar
y venules of the intestine (54 +/- 12 vs. 6 +/- 4/mu m(2) in sham-operated
control animals) and in the postsinusoidal venules of the liver (32 +/- 8 v
s. 2 +/- 2/mu m(2) in sham-operated control animals). Concomitantly, the gr
anulocyte count was increased (9.1 +/- 0.6 vs. 2.1 +/- 0.3% of total circul
ating leukocytes in sham-operated control animals), with an increase of CD
11b expression. Aminoguanidine administration (1 mg/kg) 0.5 hour before isc
hemia and 1 hour after reperfusion significantly increased MAP, increased i
ntestine and liver perfusion, decreased adhesion, and decreased circulating
granulocytes and CD 11b expression.
Conclusion: Inhibition of an inducible NO release by aminoguanidine in inte
stinal I/R can attenuate hemodynamic and microcirculatory derangement.