The Nutritional Status Modulates Preservation-Reperfusion Injury in Rat Fatty Liver Paolo Caraceni,* , † ,1 Marco Domenicali,* , † Anna Maria Pertosa,* , † Elisabetta Maiolini,* Ignazio Grattagliano,‡ Alessandro Principe,* , † Giuseppe Palasciano,‡ Franco Trevisani,* and Mauro Bernardi* , † *Department of Internal Medicine, Cardioangiology, and Hepatology, University of Bologna, Bologna, Italy; †Center for Biomedical Applied Research (C.R.B.A.), University of Bologna, Bologna, Italy; and ‡Department of Internal Medicine and Public Health, University of Bari, Bari, Italy Submitted for publication October 28, 2004 Background. Microcirculation disturbances are es- sential factors of preservation injury in fatty liver. However, hepatocyte injury is also markedly excessive in fatty liver resulting, at least in part, from energy metabolism impairment and oxidative stress. Thus, this study aimed to determine whether nutritional sta- tus influences preservation injury in fatty liver and whether energetic substrate supplementation, alone or with a vasodilator, is protective. Materials and methods. Normal or fatty livers in- duced by a choline-deficient diet were isolated from fed and fasted rats, preserved in University of Wiscon- sin solution at 4°C for 18 h, and then reperfused with Krebs–Henseleit solution at 37°C for 120 min. Fasted rats with fatty liver were also treated as follows: (1) Glucose supplementation: rats had access to a glucose solution for 18 h prior procurement; (2) Prostaglandin (PG): alprostadil was continuously infused during reperfusion; (3) Combined treatment: Glucose supple- mentation  PG. Results. Fasting-induced liver injury was signifi- cantly greater in fatty than normal liver. In fatty livers from fasted rats, all treatments reduced the alanine aminotransaminase release. Hepatic oxygen consump- tion improved in the glucose and glucose  PG groups, while PG infusion had no effect. Glucose supplemen- tation did not affect portal pressure, which, in con- trast, was reduced in livers receiving PG. Finally, all treatments lowered oxidative injury. Conclusions. Preservation injury in fatty liver is greatly related to nutritional status. Energetic sub- strate supplementation may represent a clinically fea- sible protective strategy and a multistep approach adding vasodilators could offer further benefit by act- ing on different pathogenetic mechanisms. © 2005 Elsevier Inc. All rights reserved. Key Words: fatty liver; experimental liver transplan- tation; preservation injury; reperfusion injury; nutri- tional status; prostaglandins. INTRODUCTION Fatty liver is the most frequent alteration of the liver found in the general population and its prevalence reaches about 25% of the potential donors for ortho- topic liver transplantation and living donor liver trans- plantation. The presence of fatty degeneration reduces the tolerance of the liver to the ischemia-reperfusion injury invariably associated with these surgical proce- dures, leading to higher mortality and postoperative complication rates. Thus, albeit the persistent short- age of donor organs, most centers do not transplant livers with moderate-massive fatty infiltration [1]. Impaired microcirculation has been proposed as the key event in the pathogenesis of preservation- reperfusion injury in steatotic livers [1]. The sinusoidal blood flow is greatly reduced after transplantation of fatty livers as the result of the narrowed sinusoidal lumen, which is compressed by the swollen fat-loaded hepatocytes and partially or completely obstructed by cell debris and platelets and leukocytes adherent to the endothelium [1–3]. Thus, it is not surprising that sub- stances with vasodilator and antiinflammatory proper- ties, such as prostaglandins, have been found to be protective in animal models of fatty liver transplanta- tion [4, 5]. However, other evidences indicate that hepatocyte 1 To whom correspondence and reprint requests should be ad- dressed at Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, University of Bologna, Policlinico Sant’Orsola, Via Al- bertoni 15, 40138 Bologna, Italy. E-mail: paolo.caraceni@unibo.it. Journal of Surgical Research 127, 190 –196 (2005) doi:10.1016/j.jss.2005.02.018 190 0022-4804/05 $30.00 © 2005 Elsevier Inc. All rights reserved.