RESUMO
The Institut Georges Lopez preservation solution (IGL-1) is a serum-free organ preservative that has been shown to protect steatotic livers against hepatic ischemia-reperfusion injury. Although several hypotheses have been proposed to explain the graft protection mechanisms induced by IGL-1 solution, they have not been fully investigated. This review assessed possible IGL-1 mechanisms responsible for the increased liver tolerance of ischemia-reperfusion injury with special emphasis on vasodilatator mediators such as nitric oxide, on oxidative stress prevention, on protection against mitochondrial damage, and finally on induction of cytoprotective factors.
Assuntos
Fígado Gorduroso/complicações , Soluções para Preservação de Órgãos , Traumatismo por Reperfusão/prevenção & controle , Humanos , Traumatismo por Reperfusão/etiologiaRESUMO
AIM: Static preservation solution is critical for liver graft outcomes, especially when steatosis is present. Institut Georges Lopez (IGL)-1 solution protects fatty livers effectively against cold ischemia reperfusion injury. Its benefits are mediated by nitric oxide and prevention of oxidative stress. The supplementation of IGL-1 with epidermal growth factor (EGF) enhances steatotic graft preservation by increasing adenosine triphosphate content, thereby mitigating oxidative stress and mitochondrial damage. METHODS: After steatotic livers were preserved for 24 hours in IGL-1 solution with or without EGF supplements, they were perfused ex vivo for 2 hours at 37°C. The benefits of EGF were assessed by evidences of hepatic damage and function--transaminases, bile production, and flow rate--as well as by other factors presumably associated with the poor tolerance of fatty livers toward cold ischemia-reperfusion injury (IRI)--energy metabolism, mitochondrial damage, oxidative stress, eNOS activity and proinflammatory interleukin (IL) beta content. RESULTS: Steatotic livers preserved in IGL-1 solutions supplemented with EGF (10 µg/L) showed lower transaminase levels, greater bile production, and ameliorated flow rates when compared to IGL-1 alone. In addition, energy metabolism deterioration, mitochondrial damage, oxidative stress, and cytokine IL-1 beta release were prevented. CONCLUSION: EGF addition to IGL-1 increased fatty liver graft preservation, thereby reducing steatotic liver damage against cold IRI.
Assuntos
Fator de Crescimento Epidérmico/administração & dosagem , Fígado Gorduroso/patologia , Preservação Biológica , Animais , Western Blotting , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Ratos , SoluçõesAssuntos
Adenosina , Alopurinol , Glutationa , Insulina , Fígado , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Propilenoglicóis/farmacologia , Rafinose , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Creatinina/sangue , Fígado/efeitos dos fármacos , Fígado/fisiologia , Circulação Hepática/fisiologia , Testes de Função Hepática , Suínos , Ureia/sangueAssuntos
Aorta Abdominal , Fígado/fisiologia , Soluções para Preservação de Órgãos , Perfusão/métodos , Veia Porta , Adenosina , Alanina Transaminase/sangue , Alopurinol , Animais , Aspartato Aminotransferases/sangue , Pressão Sanguínea , Glucose/metabolismo , Glutationa , Insulina , Fígado/irrigação sanguínea , Fígado/citologia , Masculino , Rafinose , Ratos , Ratos Wistar , Ureia/metabolismoAssuntos
Fígado/fisiopatologia , Soluções para Preservação de Órgãos , Perfusão/normas , Adenosina , Alopurinol , Animais , Glutationa , Insulina , Masculino , Rafinose , Ratos , Ratos Wistar , SoluçõesAssuntos
Rim , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Adenosina , Trifosfato de Adenosina/metabolismo , Alopurinol , Animais , Temperatura Baixa , Taxa de Filtração Glomerular , Glutationa , Técnicas In Vitro , Insulina , Rim/patologia , Rim/fisiologia , Glomérulos Renais/patologia , Necrose Tubular Aguda/patologia , Perfusão , Fosfocreatina/metabolismo , Rafinose , Ratos , Fatores de TempoRESUMO
The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K+ UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na+ UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na+ UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K+ UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na+ UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na+ UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K+ UW solution. Liver preservation in the high-Na+ UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution.