Role of ischemic preconditioning and the portosystemic shunt in the prevention of liver and lung damage after rat liver transplantation1

Background. This study evaluates whether surgical strategies such as the portosystemic shunt and ischemic preconditioning can protect against hepatic and pulmonary injury associated with liver transplantation. Methods. The effect of the portosystemic shunt, ischemic preconditioning, and both surgical procedures together were evaluated in rat liver transplantation. Alanine aminotransferase, hyaluronic acid levels in plasma, adenosine triphosphate and nucleotide levels in liver and edema, malondialdehyde levels, and myeloperoxidase activity were measured 24 hr posttransplantation. Plasmatic tumor necrosis factor (TNF) levels were measured as a possible proinflammatory factor responsible for hepatic and pulmonary damage associated with liver transplantation Results. Hepatocyte and cell endothelial damage were observed in liver grafts subjected to 8 hr of cold ischemia. This was associated with increased plasma TNF levels and lung inflammatory response. Portosystemic shunt application in the recipient protected endothelial cells but did not confer an effective protection from hepatocyte damage or reduce the increased plasma TNF levels and lung damage after liver transplantation. However, preconditioning of the donor liver conferred protection against both the endothelial cell and hepatocyte damage observed after liver transplantation. Preconditioning also attenuated the increased plasma TNF release and pulmonary damage. The combination of both surgical strategies resulted in levels of liver injury, TNF, and lung damage similar to those seen after liver transplantation. Conclusions. These findings indicate that ischemic preconditioning could be a preferred treatment to reduce hepatic and pulmonary damage associated with liver transplantation. However, this strategy may not be effective in several clinical situations requiring a portosystemic shunt.

[1]  J. Lemasters,et al.  Ischemic preconditioning of rat livers against cold storage‐reperfusion injury: Role of nonparenchymal cells and the phenomenon of heterologous preconditioning , 2001, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[2]  K. Man,et al.  Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes. , 2001, Archives of surgery.

[3]  N. Habib,et al.  Hepatic ischemia-reperfusion injury. , 2001, American journal of surgery.

[4]  M. Sans,et al.  Preconditioning protects against systemic disorders associated with hepatic ischemia‐reperfusion through blockade of tumor necrosis factor–induced P‐selectin up‐regulation in the rat , 2001, Hepatology.

[5]  E. Jaurrieta,et al.  Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study , 2000, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[6]  M. Miyazaki,et al.  Mechanism of cold ischemia-reperfusion-induced graft injury after orthotopic liver transplantation in rats. , 2001, Hepato-gastroenterology.

[7]  R. Wiesner,et al.  Hypoxia decreases proteins involved in epithelial electrolyte transport in A549 cells and rat lung. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[8]  A. Brault,et al.  Role of Kupffer cells in the survival after rat liver transplantation with long portal vein clamping times , 2000, Transplant international : official journal of the European Society for Organ Transplantation.

[9]  J. Tillement,et al.  S-15176 reduces the hepatic injury in rats subjected to experimental ischemia and reperfusion. , 2000, European journal of pharmacology.

[10]  M. Unno,et al.  Correlation between plasma and hepatic phosphatidylcholine hydroperoxide, energy charge, and total glutathione content in ischemia reperfusion injury of rat liver. , 2000, Hepato-gastroenterology.

[11]  R. Bartrons,et al.  Hepatic preconditioning preserves energy metabolism during sustained ischemia. , 2000, American journal of physiology. Gastrointestinal and liver physiology.

[12]  J. Roselló-Catafau,et al.  Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia‐reperfusion in the rat , 1999, Hepatology.

[13]  C. Herfarth,et al.  Ischemic preconditioning improves liver microcirculation after ischemia/reperfusion. , 1999, Transplantation proceedings.

[14]  S. Raia,et al.  Pulmonary evolution in conventional liver transplantation with venovenous bypass and the piggyback method. , 1999, Transplantation proceedings.

[15]  A. Chong,et al.  The portosystemic shunt protects liver against ischemic reperfusion injury. , 1999, Transplantation.

[16]  J. Roselló-Catafau,et al.  The protective role of adenosine in inducing nitric oxide synthesis in rat liver ischemia preconditioning is mediated by activation of adenosine A2 receptors , 1999, Hepatology.

[17]  T. Sakaguchi,et al.  Pathophysiological appraisal of a rat model of total hepatic ischemia with an extracorporeal portosystemic shunt. , 1998, The Journal of surgical research.

[18]  C. Herfarth,et al.  Definition of maximum cold ischemia time without reduction of graft quality in clinical liver transplantation. , 1998, Transplantation proceedings.

[19]  P. Reggiani,et al.  Veno-venous bypass versus no bypass in orthotopic liver transplantation: hemodynamic, metabolic, and renal data. , 1998, Transplantation proceedings.

[20]  A. Chong,et al.  Protective effect of ischemic preconditioning on liver preservation-reperfusion injury in rats. , 1998, Transplantation.

[21]  K. Fujiwara,et al.  Selective bowel decontamination of recipients for prevention against liver injury following orthotopic liver transplantation: Evaluation with rat models , 1998, Hepatology.

[22]  J. Roselló-Catafau,et al.  Protective effect of preconditioning on the injury associated to hepatic ischemia‐reperfusion in the rat: Role of nitric oxide and adenosine , 1997, Hepatology.

[23]  N. Ohkohchi,et al.  Kupffer cells generate superoxide anions and modulate reperfusion injury in rat livers after cold preservation , 1997, Hepatology.

[24]  M. Zeniya,et al.  Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat. , 2008, Liver.

[25]  R. Chamuleau,et al.  Hyaluronic acid uptake in the assessment of sinusoidal endothelial cell damage after cold storage and normothermic reperfusion of rat livers , 1996, Transplant international : official journal of the European Society for Organ Transplantation.

[26]  T. Sakaguchi,et al.  Role of Kupffer cells and the spleen in modulation of endotoxin‐induced liver injury after partial hepatectomy , 1996, Hepatology.

[27]  H. Sankary,et al.  Do splanchnic viscera contribute to liver preservation reperfusion injury? , 1996, Transplantation.

[28]  M. Shimada,et al.  Significance of hyaluronic acid for evaluation of hepatic endothelial cell damage after cold preservation/reperfusion. , 1995, The Journal of surgical research.

[29]  M. Lerner,et al.  A new model for inducing total hepatic ischemia while preventing circulatory collapse secondary to splanchnic vascular congestion. , 1995, Shock.

[30]  E. Kobayashi,et al.  The influence of intestinal congestion on survival of preserved liver grafts in rat liver transplantation. , 1994, Transplantation.

[31]  E. Kobayashi,et al.  Portosystemic shunt for orthotopic liver transplantation in the rat. , 1994, The Journal of surgical research.

[32]  R. Bone,et al.  Role of tumor necrosis factor-α in disease states and inflammation , 1993 .

[33]  T. Starzl,et al.  Temporary end to side portacaval shunt in orthotopic hepatic transplantation in humans. , 1993, Surgery, gynecology & obstetrics.

[34]  H. Fusamoto,et al.  Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat , 1992, Hepatology.

[35]  P. Clavien,et al.  Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. , 1992, Transplantation.

[36]  A. Székely,et al.  Experimental study of the protective effect of intermittent hepatic pedicle clamping in the rat , 1992, The British journal of surgery.

[37]  I. Marzi.  HEPATIC MICROCIRCULATORY DISTRUBANCE DUE TO PORTAL VEIN CLAMPING IN THE ORTHOTOPIC RAT LIVER TRANSPLANTATION MODEL , 1991, Transplantation.

[38]  Y. Takei,et al.  Increase in survival of liver grafts after rinsing with warm Ringer's solution due to improvement of hepatic microcirculation. , 1991, Transplantation.

[39]  I. Marzi,et al.  INCREASE IN SURVIVAL TIME OF LIVER TRANSPLANTS BY PROTEASE INHIBITORS AND A CALCIUM CHANNEL BLOCKER, NISOLDIPINE , 1990, Transplantation.

[40]  R. Strieter,et al.  The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion. , 1990, Transplantation.

[41]  J. Ludwig,et al.  Comparison of University of Wisconsin (UW) and Eurocollins (EC) preservation solutions in a rat liver transplant model , 1990, Transplant international : official journal of the European Society for Organ Transplantation.

[42]  G. Klintmalm,et al.  Considerations for Anesthetic Management During Veno‐venous Bypass in Adult Hepatic Transplantation , 1989, Anesthesia and analgesia.

[43]  R. Busuttil,et al.  Air embolism associated with veno-venous bypass during orthotopic liver transplantation. , 1987, Anesthesiology.

[44]  M. Pinsky,et al.  Effect of end-stage liver failure on the incidence and resolution of the adult respiratory distress syndrome , 1987 .

[45]  R. Calne,et al.  ORTHOTOPIC LIVER TRANSPLANTATION IN THE RAT: TECHNIQUE USING CUFF FOR PORTAL VEIN ANASTOMOSIS AND BILIARY DRAINAGE , 1979, Transplantation.

[46]  S. Bengmark,et al.  Development of portasystemic shunts after subcutaneous transposition of the spleen in the rat. , 1973, American journal of surgery.