Effects of Ischemic Liver Preconditioning on Hepatic Ischemia/Reperfusion Injury in the Rat S.A.R. Centurion, L.M. Centurion, M.E.J. Souza, M.C.J. Gomes, A.K. Sankarankutty, E.D. Mente, and O. Castro e Silva ABSTRACT To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by clamping the hepatic pedicle for 5 minutes, followed by a 5-minute reperfusion (R) period before a 2-hour ischemia. Thereafter, reperfusions of 1, 3, and 24 hours were compared among IPC and control groups without IPC. Liver biopsy and blood samples were measured for mitochondrial respiratory control ratio (RCR), serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IPC protected liver mitochondrial function. Serum aminotransferase levels were significantly lower among animals undergoing IPC compared with groups without IPC. Thus, we verified the effects of IPC for hepatocellular protection against I/R lesions. T HE MEDICAL LITERATURE has shown that both patients and experimentation animals undergoing liver transplantation or major liver resection after pro- longed ischemia periods show fewer severe hemorrhages requiring transfusions. 1 However, hepatocellular-induced ischemia ends to hemodynamic, cellular, and tissue lesions with variable intensity, depending on the period of vascular exclusion. 2 Later, during reperfusion, it seems that the cellular alterations of ischemia-reperfusion (I/R) may lead to serious systemic and hepatic repercussions. 3 Settaf et al 4 used trimetazidine to prevent I/R lesions during surgeries for hepatic hydatid cysts during the period of vascular clamping of the hepatic pedicle. These results suggested that trimetazidine reduced the I/R lesion during the surgery, and might allow longer ischemia periods with- out further liver damage. Ischemic preconditioning (IPC) was introduced by Murry et al. 5 It refers to brief ischemia episodes before a pro- longed period followed by reperfusion. It has been shown to protect organs against I/R injury. 6 The role of IPC in tolerance to the ischemia has been described in several organs beside the liver, including the heart, brain, spinal cord, skeletal muscles, retina, kidneys, and intestines. However, despite the studies on mechanisms of IPC, its basis has not been clearly established. 8 Peralta et al 8 have suggested that IPC protects against systemic disorders associated with I/R by blocking tumor necrosis factor (TNF) release by Kupffer cells and by inducing increased activated adenosine monophosphate kinase (AMP-K) during prolonged ischemia. This effect leads to preservation of adenosine triphosphate (ATP), reduced lactate accumulation during the ischemia, and postreperfusion hepatic damage. 9 IPC seems to be a pro- tective mechanism mitigation of that reduces I/R-induced hepatocellular lesions. 7 The aim of the present study was to assess the preconditioning ischemic effect in animals sub- mitted to hepatic I/R. From the Special Liver Transplantation Unit, Departments of Surgery and Anatomy, Ribeirão Preto School of Medicine, Uni- versity of São Paulo (M.E.J.S., M.C.J.G., A.K.S., E.D.M., O.C.), and Catanduva School of Medicine (S.A.R.C., L.M.C.), São Paulo, Brazil. Supported by FAPESP and CNPq. Address reprint requests to Prof Orlando de Castro e Silva, Departments of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3.900 - CEP 14049-900, Ribeirão Preto, São Paulo, Brasil. E-mail: orlando@fmrp.usp.br © 2007 by Elsevier Inc. All rights reserved. 0041-1345/07/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2007.01.011 Transplantation Proceedings, 39, 361–364 (2007) 361