title: Simvastatin maintains function and viability of steatotic rat livers procured for transplantation.
abstract: OBJECTIVE
  Liver grafts obtained from healthy rat donors develop acute microcirculatory dysfunction due to cold-storage and warm-reperfusion injuries. These detrimental effects are avoided adding simvastatin to the cold-storage solution. Considering the importance of increasing organ donor pool for transplantation, we characterized whether simvastatin pretreatment can protect steatotic grafts from cold-storage and warm-reperfusion injuries.
  
  
  METHODS
  Rats fed with high-fat diet received a single dose of simvastatin, or its vehicle, 30 min before liver procurement. Grafts were then cold stored for 0 h (control group) or 16 h and warm reperfused. At the end of the reperfusion period, hepatic vascular resistance, endothelial function, nitric oxide pathway, cell death, oxidative stress, autophagy, and liver injury were evaluated. Hepatic vascular resistance and endothelial function were determined in a group of simvastatin-treated livers in the presence of the nitric oxide synthase inhibitor L-NNA.
  
  
  RESULTS
  Cold-stored rat steatotic livers exhibit increased hepatic vascular resistance and marked endothelial dysfunction, together with liver damage, oxidative stress, and low nitric oxide. Simvastatin markedly improved liver injury and prevented hepatic endothelial dysfunction. The beneficial effects of simvastatin were associated with cell death diminution, autophagy induction, and nitric oxide release. Statin-derived liver microcirculation protection was not observed when nitric oxide production was blunted.
  
  
  CONCLUSIONS
  Pretreatment of steatotic liver donors with simvastatin shortly before procurement of the liver graft strongly protects both parenchymal and endothelial components of the liver after warm reperfusion. Our data reinforce the use of statins to protect liver grafts undergoing transplantation.
authors: Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Spain. jgracia@clinic.ub.es
authors: Jordi
authors: J
authors: Gracia-Sancho
authors: Héctor
authors: H
authors: García-Calderó
authors: Diana
authors: D
authors: Hide
authors: Giusi
authors: G
authors: Marrone
authors: Sergi
authors: S
authors: Guixé-Muntet
authors: Carmen
authors: C
authors: Peralta
authors: Juan Carlos
authors: JC
authors: García-Pagán
authors: Juan G
authors: JG
authors: Abraldes
authors: Jaime
authors: J
authors: Bosch
mesh_terms: D000818:Animals; D015925:Cryopreservation; D005234:Fatty Liver / Q000503:physiopathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin