Our studies characterized the intestinal microcirculatory changes in canine models of intestinal hypoperfusion (
hemorrhagic shock) or
ischemia-reperfusion (small bowel
autotransplantation). The villus microcirculatory parameters (functional capillary density, mean red blood cell velocity) were observed by intravital microscopy using orthogonal polarization spectral imaging. The leukocyte reaction (rolling and firm adherence) in the mesentery was quantified by using conventional fluorescence videomicroscopy. The investigations were aimed at determining whether the compromised intestinal villus perfusion could be influenced by
endothelin-A receptor inhibition, volume
resuscitation, or ischemic preconditioning. The results demonstrated the pathophysiological significance of
endothelin-A receptor activation in
ischemia-reperfusion-induced microcirculatory changes. Second, it was shown that
colloid fluid therapy with hydroxyethyl-
starch effectively ameliorated the microcirculatory consequences of
hypovolemia, which correlated with a lower
endothelin release. Third, ischemic preconditioning when applied 60 minutes before
ischemia, inhibited the reperfusion-induced
superoxide production, improved capillary perfusion, and attenuated leukocyte activation within the intestinal graft. Among the examined therapeutic strategies aimed at improving the outcome of intestinal microcirculatory dysfunction,
endothelin-A receptor antagonist pretreatment and ischemic preconditioning are promising tools to decrease the harmful consequences of
ischemia/reperfusion.