title: Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning.
abstract: Hepatic ischemia/reperfusion injury has immediate and deleterious effects on the outcome of patients after liver surgery. The precise mechanisms leading to the damage have not been completely elucidated. However, there is substantial evidence that the generation of oxygen free radicals and disturbances of the hepatic microcirculation are involved in this clinical syndrome. Microcirculatory dysfunction of the liver seems to be mediated by sinusoidal endothelial cell damage and by the imbalance of vasoconstrictor and vasodilator molecules, such as endothelin (ET), reactive oxygen species (ROS), and nitric oxide (NO). This may lead to no-reflow phenomenon with release of proinflammatory cytokines, sinusoidal plugging of neutrophils, oxidative stress, and as an ultimate consequence, hypoxic cell injury and parenchymal failure. An inducible potent endogenous mechanism against ischemia/reperfusion injury has been termed ischemic preconditioning. It has been suggested that preconditioning could inhibit the effects of different mediators involved in the microcirculatory dysfunction, including endothelin, tumor necrosis factor-alpha, and oxygen free radicals. In this review, we address the mechanisms of liver microcirculatory dysfunction and how ischemic preconditioning could help to provide new surgical and/or pharmacological strategies to protect the liver against reperfusion damage.
authors.affiliation: Laboratory of Experimental Liver Pathology, Department of Clinical and Biological Sciences, University of Torino, Italy. juancarlos.cutrin@unito.it
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cutrn
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Perrelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Cavalieri
authors.forename: Carmen
authors.initials: C
authors.lastname: Peralta
authors.forename: Joan
authors.initials: J
authors.lastname: Rosell Catafau
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008102:Liver Circulation; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha