Pathophysiology of ischemia-reperfusion injury

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.