Bile Duct Exclusion From Selective Vascular Inflow Occlusion in Rat Liver: Role of Ischemic Preconditioning and N-Acetylcysteine on Hepatic Reperfusion Injury E.F.S. Montero, C. Quireze Jr, and D.M.R. d’Oliveira ABSTRACT Aim. To study the effects of N-acetylcysteine and ischemic preconditioning on the portal triad clamping compared to arterial and portal clamping alone. Methods. Eighty EPM 1-Wistar rats were randomized into two groups, depending on inclusion (Group 1) or not (Group 2) of the bile duct in the hepatic vascular pedicle occlusion. Each group was divided into four subgroups as follows. IR 1: 20 minutes after celiotomy, the pedicle containing vascular elements and bile duct to the left lateral and median liver lobes was occluded for 40 minutes, followed by 30 minutes of reperfusion. IPC 1: after 10 minutes of ischemia and 10 minutes of reperfusion, the ischemic precondition- ing period, the rats were submitted to the same procedure described for IR 1 Group. NAC 1: the rats received N-acetylcysteine (150 mg/kg) 15 minutes before 40 minutes of ischemia and 5 minutes before 30 minutes of reperfusion. SHAM 1: The hepatic pedicle for the lateral and median liver lobes was dissected after 20 minutes, the bile duct alone was clamped for 40 minutes, and released for an additional 30 minutes. In the IR 2, IPC 2, and NAC 2 groups, ischemia was achieved with an exclusive vascular occlusion. SHAM 2: dissection and observation for 90 minutes. The blood was sampled for liver enzyme levels. Statistical analysis was done (P  .05). Results. Hepatic IR injury was less severe for animals from the classic portal triad clamping (group 1), with regard to AST (IR 1 Group 766 vs IR 2 Group 1380 U/L) and ALT (IR 1 Group 840 vs IR 2 Group 1576 U/L); IPC, but not NAC administration, was able to protect the liver from IR injury for animals from the classic portal triad clamping group, with regard to AST (IPC 1 Group 421 vs NAC 1 Group 1131 U/L) and ALT (IPC 1 Group 315 vs NAC 1 Group 1085 U/L). Conclusions. IPC protects the liver from IR injury; classic portal triad clamping results in a less severe hepatic IR injury when compared to bile duct exclusion. I MPAIRED liver function and patient mortality may result from prolonged vascular inflow occlusion, during complex hepatic surgery. Evidence favoring different path- ways of injury to liver cells, such as hepatocytes, sinusoidal lining cells, as well as bile duct cells, has encouraged the evaluation of some strategies to minimize damage or re- store liver function after the ischemia-reperfusion (IR) insult. 1–4 Concerning ischemic preconditioning (IPC), it has been shown to be useful in down-regulating apoptotic death for both hepatocytes and sinusoidal cells. 5–8 In that context, administration of N-acetylcysteine (NAC) has been shown to improve the microcirculation, decreasing nonreperfused sinusoids, so as to protect against oxidative stress and enhance reduced glutathione. 9 –12 Although those benefits are well documented, there is little data available with regard to the role of the biliary tree on hepatic IR injury. From the Federal University of São Paulo (E.F.S.M., D.M.R.O.), São Paulo, Brazil, and Federal University of Goiás (C.Q.), Goiânia, Brazil. This work was supported by CNPq and CAPES. Address reprint requests to Dr Edna Frasson de Souza Montero, Alameda Espada, 134—Alphaville 11—Santana de Parnaı´ba 06540- 395, SP, Brazil. E-mail: efsmontero@terra.com.br © 2005 by Elsevier Inc. All rights reserved. 0041-1345/05/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2004.12.194 Transplantation Proceedings, 37, 425– 427 (2005) 425