IN-VIVO ANALYSIS OF MICROVASCULAR REPERFUSION INJURY IN STRIATED-MUSCLE AND SKIN

The use of intravital fluorescence microscopy in the models of the hamster dorsal skin fold chamber and the ear of the hairless mouse allows for the quantitative analysis of post-ischemic microvascular reperfusion injury in striated muscle and skin. Prolonged periods of ischemia (4 hours in striated muscle and 6 hours in skin) are associated with 1) perfusion failure of nutritive capillaries at the onset of reperfusion (no-reflow) and 2) activation, accumulation and microvascular adherence of white blood cells, formation of reactive oxygen metabolites and release of potent mediators (leukotrienes, platelet-activating factor) with the consequence of increased microvascular permeability due to the loss of endothelial integrity, interstitial edema and-cell damage (reflow-paradox). Prophylactic and/or therapeutic regimens may, therefore, include improvement of capillary perfusion by hemodilution, and inhibition of leukocyte adherence, radical formation and mediator release by appropriate counteracting compounds, including anti-oxidants, antibodies directed against adhesion molecules, leukotriene synthesis inhibitors and platelet-activating factor receptor antagonists.