%0 Journal Article
%T Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811
%A Qinlong Liu
%A Hasibur Rehman
%A Russell A. Harley
%A John J. Lemasters
%A Zhi Zhong
%J HPB Surgery
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/270372
%X Pulmonary complications after liver transplantation (LT) often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5£¿ M) for 6£¿h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG) and quarter-size grafts (QSG), respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5¨C18£¿h after LT. At 38£¿h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNF and IL-1¦Â mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT. 1. Introduction Pulmonary complications including acute lung injury and acute respiratory distress syndrome frequently occur after liver transplantation (LT) and contribute significantly to perioperative and postoperative morbidity and mortality [1¨C4]. The frequency of pulmonary complications is reported as high as 75% in some studies [1], and the mortality rate for acute respiratory distress syndrome reaches 50%¨C80% [2, 5]. Prolonged cold storage, retrieval procedures, intraoperative transfusion of plasma-containing blood products, ischemia/reperfusion- (I/R-) induced graft injury, proinflammatory cytokine and chemokine formation, leukocyte recruitment and release of neutrophil elastase, pulmonary endothelial barrier disruption, and vascular hyperpermeability possibly play critical role in the development of posttransplantation acute lung injury [1, 2, 5¨C8]. Since primary liver graft failure is often associated with pulmonary injury, prevention and treatment of pulmonary complications could improve the outcome of LT. Due to severe shortage of donor organs, partial LT has
%U http://www.hindawi.com/journals/hpb/2012/270372/