REMODELING OF HEPATIC MICROVASCULAR RESPONSIVENESS AFTER ISCHEMIA REPERFUSION/

Although there is substantial evidence suggesting that the integrity o f the microcirculation is an important determinant of tissue viability during reperfusion after ischemia in the liver, as well as other tiss ues, the mechanisms responsible for microvascular failure are not full y understood. It is now recognized that the microvascular response to reperfusion, similar to the whole organism response to shock, can cons ist of either a rapid exacerbation of injury after a severe ischemic e pisode or, alternatively, a more slowly developing alteration in respo nsiveness that occurs after a less severe insult. In the more slowly d eveloping response, the alterations in vascular status are the result of up-regulation of stress-induced vascular mediators such as endothel in, nitric oxide synthase (NOS), and heme oxygenase, as well as change s in the reactivity of the effector cells to the mediators. The mechan isms for change in reactivity of vascular cells range from changes in receptor expression to overt phenotypic transformation, as can occur i n the hepatic stellate cells in response to repeated injury. When main tained in balance, these counteracting constrictor and dilator influen ces can be protective; however, local imbalance can result in focal is chemia, thus propagating the injury. Thus, the remodeling of the hepat ic microvascular responsiveness during reperfusion after ischemia may serve as a useful paradigm for consideration of the overall response o f the organism to shock.