Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion)...Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.展开更多
BACKGROUND: The quality of liver graft and outcome of liver transplantation is affected by the length of ischemia time during the donor operation. The retrieved graft may have a serious damage during the time of stopp...BACKGROUND: The quality of liver graft and outcome of liver transplantation is affected by the length of ischemia time during the donor operation. The retrieved graft may have a serious damage during the time of stoppage of the circulation in the donor until revascularization in the recipient. It is very important to develop a suitable preservation fluid to minimise the damage caused by the ischemic period and to make the surgical procedure semi- elective. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1960-2006) on liver preservation solution, liver transplantation, kidney transplantation and other related subjects. RESULTS: Since 1960 until 2006 many preservation solutions have been introduced. Most of them are based on the effect of hypothermia to minimise the metabolic pathway in the liver graft. In the earlier studies electrolyte solutions were used to perfuse the liver through the portal vein. The first modification in preservation solution was done by Collins who was able to extend the kidney preservation time up to 30 hours. In recent years, the introduction of University of Wisconsin (UW) preservation solution has made a revolution in the field of organ preservation. The UW solution is based on lactobionate and raffinose as impermeants to suppress hypothermic-induced tissue swelling, replacing glucose and mannitol in Collin's solution and hypertonic citrate respectively. Recently a research group in Kyoto University works to produce a more reliable preservation solution. They investigated the importance of saccharides and electrolytes in lung preservation and developed their original ET-Kyoto solution. However, more studies are still needed to evaluate the new ET-Kyoto solution. CONCLUSIONS: The development of new preservation solutions represents a corner stone in the field of organtransplantation. In the future we might be able to extend the time of organ preservation from hours to days.展开更多
AIM： Chronic organ-donor shortage has led to the acceptance of steatotic livers for transplantation, despite the higher risk of graft dysfunction or nonfunction associated with the ischemic preservation period of the...AIM： Chronic organ-donor shortage has led to the acceptance of steatotic livers for transplantation, despite the higher risk of graft dysfunction or nonfunction associated with the ischemic preservation period of these organs. The present study evaluates the effects of trimetazidine （TMZ） on an isolated perfused liver model. METHODS： Steatotic and non-steatotic livers were preserved for 24 h in the University of Wisconsin （UW） solution with or without TMZ. Hepatic injury and function （transaminases, bile production and sulfobromophthalein （BSP） clearance） and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion （I/R） injury, including oxidative stress, mitochondrial damage, microcirculatory diseases, and ATP depletion were evaluated. RESULTS： Steatotic livers preserved in UW solution showed higher transaminase levels, lower bile production and BSP clearance compared with non-steatotic livers. Alterations in perfusion flow rate and vascular resistance, mitochondrial damage, and reduced ATP content were more evident in steatotic livers. TMZ addition to UW solution reduced hepatic injury and ameliorated hepatic functionality in both types of the liver and protected against the mechanisms potentially responsible for the poor tolerance of steatotic livers to I/R. CONCLUSION： TMZ may constitute a useful approach in fatty liver surgery, limiting the inherent risk of steatotic liver failure following transplantation.展开更多
基金Supported by Fondo de Investigaciones Sanitarias,Ministerio de Economía y Competitividad(Madrid,Spain)No.PI15/00110
文摘Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.
文摘BACKGROUND: The quality of liver graft and outcome of liver transplantation is affected by the length of ischemia time during the donor operation. The retrieved graft may have a serious damage during the time of stoppage of the circulation in the donor until revascularization in the recipient. It is very important to develop a suitable preservation fluid to minimise the damage caused by the ischemic period and to make the surgical procedure semi- elective. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1960-2006) on liver preservation solution, liver transplantation, kidney transplantation and other related subjects. RESULTS: Since 1960 until 2006 many preservation solutions have been introduced. Most of them are based on the effect of hypothermia to minimise the metabolic pathway in the liver graft. In the earlier studies electrolyte solutions were used to perfuse the liver through the portal vein. The first modification in preservation solution was done by Collins who was able to extend the kidney preservation time up to 30 hours. In recent years, the introduction of University of Wisconsin (UW) preservation solution has made a revolution in the field of organ preservation. The UW solution is based on lactobionate and raffinose as impermeants to suppress hypothermic-induced tissue swelling, replacing glucose and mannitol in Collin's solution and hypertonic citrate respectively. Recently a research group in Kyoto University works to produce a more reliable preservation solution. They investigated the importance of saccharides and electrolytes in lung preservation and developed their original ET-Kyoto solution. However, more studies are still needed to evaluate the new ET-Kyoto solution. CONCLUSIONS: The development of new preservation solutions represents a corner stone in the field of organtransplantation. In the future we might be able to extend the time of organ preservation from hours to days.
文摘AIM： Chronic organ-donor shortage has led to the acceptance of steatotic livers for transplantation, despite the higher risk of graft dysfunction or nonfunction associated with the ischemic preservation period of these organs. The present study evaluates the effects of trimetazidine （TMZ） on an isolated perfused liver model. METHODS： Steatotic and non-steatotic livers were preserved for 24 h in the University of Wisconsin （UW） solution with or without TMZ. Hepatic injury and function （transaminases, bile production and sulfobromophthalein （BSP） clearance） and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion （I/R） injury, including oxidative stress, mitochondrial damage, microcirculatory diseases, and ATP depletion were evaluated. RESULTS： Steatotic livers preserved in UW solution showed higher transaminase levels, lower bile production and BSP clearance compared with non-steatotic livers. Alterations in perfusion flow rate and vascular resistance, mitochondrial damage, and reduced ATP content were more evident in steatotic livers. TMZ addition to UW solution reduced hepatic injury and ameliorated hepatic functionality in both types of the liver and protected against the mechanisms potentially responsible for the poor tolerance of steatotic livers to I/R. CONCLUSION： TMZ may constitute a useful approach in fatty liver surgery, limiting the inherent risk of steatotic liver failure following transplantation.
