Nazia Selzner1, Markus Selzner, Wolfram Jochum, Pierre-Alain Clavien. 1. Laboratory of Liver Transplantation and Hepatobiliary Surgery, Department of Visceral Surgery and Transplantation, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
Abstract
BACKGROUND/AIMS: Hepatic steatosis is a major risk factor for liver surgery and transplantation. The increased susceptibility of fatty livers to ischemic injury is associated with a necrotic form of cell death as opposed to apoptosis in lean animals, and is possibly related to low contents of ATP. Ischemic preconditioning, a brief period of ischemia prior to a prolonged period, protects the lean liver against ischemia through anti-apoptotic properties. We evaluated whether ischemic preconditioning also confers protection in the fatty liver and whether it protects against the ATP loss. METHODS: The effect of ischemic preconditioning was tested in steatotic and lean livers subjected to 75 min of ischemia and 4 or 24 h of reperfusion. Tissue ATP contents were assessed at various times, and a model of low hepatic ATP contents (starvation) was studied to assess the type of injury following ischemia and the effects of preconditioning. RESULTS: Ischemic preconditioning protected steatotic livers against massive necrosis. ATP levels were significantly higher before and after reperfusion in liver subjected to preconditioning when compared to controls. Liver with low baseline ATP levels (starvation) were also associated with necrosis, and were protected by ischemic preconditioning. CONCLUSIONS: Ischemic preconditioning mainly protects the fatty liver against necrosis possibly through preservation and restoration of tissue ATP contents.
BACKGROUND/AIMS: Hepatic steatosis is a major risk factor for liver surgery and transplantation. The increased susceptibility of fatty livers to ischemic injury is associated with a necrotic form of cell death as opposed to apoptosis in lean animals, and is possibly related to low contents of ATP. Ischemic preconditioning, a brief period of ischemia prior to a prolonged period, protects the lean liver against ischemia through anti-apoptotic properties. We evaluated whether ischemic preconditioning also confers protection in the fatty liver and whether it protects against the ATP loss. METHODS: The effect of ischemic preconditioning was tested in steatotic and lean livers subjected to 75 min of ischemia and 4 or 24 h of reperfusion. Tissue ATP contents were assessed at various times, and a model of low hepatic ATP contents (starvation) was studied to assess the type of injury following ischemia and the effects of preconditioning. RESULTS:Ischemic preconditioning protected steatotic livers against massive necrosis. ATP levels were significantly higher before and after reperfusion in liver subjected to preconditioning when compared to controls. Liver with low baseline ATP levels (starvation) were also associated with necrosis, and were protected by ischemic preconditioning. CONCLUSIONS:Ischemic preconditioning mainly protects the fatty liver against necrosis possibly through preservation and restoration of tissue ATP contents.
Authors: Christopher D Anderson; Gundumi Upadhya; Kendra D Conzen; Jianlou Jia; Elizabeth M Brunt; Venkataswarup Tiriveedhi; Yan Xie; Sabarinathan Ramachandran; Thalachallour Mohanakumar; Nicholas O Davidson; William C Chapman Journal: Liver Transpl Date: 2011-02 Impact factor: 5.799
Authors: Z Ben-Ari; Y Issan; Y Katz; M Sultan; M Safran; Laniado-Schwartzman Michal; G Abraham Nader; R Kornowski; F Grief; O Pappo; E Hochhauser Journal: Apoptosis Date: 2013-05 Impact factor: 4.677
Authors: Soojinna Choi; Joonhwa Noh; Ryutaro Hirose; Linda Ferell; Melanie Bedolli; John P Roberts; Claus U Niemann Journal: Ann Surg Date: 2005-03 Impact factor: 12.969
Authors: Qinlong Liu; Hasibur Rehman; Yasodha Krishnasamy; Venkat K Ramshesh; Tom P Theruvath; Kenneth D Chavin; Rick G Schnellmann; John J Lemasters; Zhi Zhong Journal: Free Radic Biol Med Date: 2012-05-15 Impact factor: 7.376
Authors: Kim H H Liss; Kyle S McCommis; Kari T Chambers; Terri A Pietka; George G Schweitzer; Sara L Park; Ilke Nalbantoglu; Carla J Weinheimer; Angela M Hall; Brian N Finck Journal: Liver Transpl Date: 2018-07 Impact factor: 5.799
Authors: Alexander Choukèr; Akio Ohta; André Martignoni; Dmitriy Lukashev; Lefteris C Zacharia; Edwin K Jackson; Jürgen Schnermann; Jerrold M Ward; Ines Kaufmann; Brenda Klaunberg; Michail V Sitkovsky; Manfred Thiel Journal: Transplantation Date: 2012-11-15 Impact factor: 4.939