In vivo microscopy of microcirculatory injury in skeletal muscle following ischemia/reperfusion.

Abstract

While the sequence of biochemical and cellular events in the pathogenesis of ischemia/reperfusion injury is increasingly well understood, the way that these processes interact at the level of microcirculation to promote a distinctive reperfusion injury is less well defined. It is becoming clear, however, that these processes are initiated at the level of microcirculation, and that microcirculatory damage may precede actual tissue injury. Such damage causes microvascular no-reflow, which in turn effectively prolongs the time of tissue ischemia and extends tissue injury. Recently, microcirculatory models have been adapted for study of the microvascular effects of ischemia/reperfusion. We have used a new in vivo mouse cremaster muscle model to study, by direct and quantitative measurement, the acute microvascular changes involved in ischemia/reperfusion. Previously described changes in capillary perfusion and venular leukocyte adhesion were observed in this model following reperfusion after prolonged ischemia (4-6 hours). We have further characterized an intense reactive vasoconstriction or vasospasm that occurs after prolonged ischemia; this vessel reaction may represent an important overlooked cause of no-reflow following ischemia/reperfusion. This article summarizes our work in the context of other available methods that have been used to define the microvascular changes of ischemia/reperfusion.