BACKGROUND： Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is...BACKGROUND： Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.展开更多
The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to red...The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.展开更多
Purpose:Ischemia and hypoxia are the main factors limiting limb replantation and transplantation.Static cold storage(SCS),a common preservation method for tissues and organs,can only prolong limb ischemia time to 4-6 ...Purpose:Ischemia and hypoxia are the main factors limiting limb replantation and transplantation.Static cold storage(SCS),a common preservation method for tissues and organs,can only prolong limb ischemia time to 4-6 h.The normothermic machine perfusion(NMP)is a promising method for the preservation of tissues and organs,which can extend the preservation time in vitro by providing continuous oxygen and nutrients.This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods.Methods:The 6 forelimbs from beagle dogs were divided into 2 groups.In the SCS group(n=3),the limbs were preserved in a sterile refrigerator at 4°C for 24 h,and in the NMP group(n=3),the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h,and the solution was changed every 6 h.The effects of limb storage were evaluated by weight gain,perfusate biochemical analysis,enzyme-linked immunosorbent assay,and histological analysis.All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance.The p value of less than 0.05 was considered to indicate statistical significance.Results:In the NMP group,the weight gained percentage was 11.72%±4.06%;the hypoxia-inducible factor-1αcontents showed no significant changes;the shape of muscle fibers was normal;the gap between muscle fibers slightly increased,showing the intercellular distance of(30.19±2.83)μm;and the vascularα-smooth muscle actin(α-SMA)contents were lower than those in the normal blood vessels.The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion,decreased after each perfusate change,and remained stable at the end of perfusion showing a peak level of 4097.6 U/L.The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L.In the SCS group,the percentage of weight gain was 0.18%±0.10%,and the contents of hypoxia-inducible factor-1αincreased gradually and reached the maximum level of(164.85±20.75)pg/mL at the end of the experiment.The muscle fibers lost their normal shape and the gap between muscle fibers increased,showing an intercellular distance of(41.66±5.38)μm.The contents of vascularα-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions:NMP caused lesser muscle damage and contained more vascularα-SMA as compared to SCS.This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.展开更多
基金supported by a grant of"Else-Kroner Fresenius Stiftung"(p49/07//A68/07)
文摘BACKGROUND： Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.
文摘The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.
基金supported by the National Key R&D Program of China(2019YFA0110704)the Military Logistic(s)Scientific Research Program of China(BHJ20J002).
文摘Purpose:Ischemia and hypoxia are the main factors limiting limb replantation and transplantation.Static cold storage(SCS),a common preservation method for tissues and organs,can only prolong limb ischemia time to 4-6 h.The normothermic machine perfusion(NMP)is a promising method for the preservation of tissues and organs,which can extend the preservation time in vitro by providing continuous oxygen and nutrients.This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods.Methods:The 6 forelimbs from beagle dogs were divided into 2 groups.In the SCS group(n=3),the limbs were preserved in a sterile refrigerator at 4°C for 24 h,and in the NMP group(n=3),the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h,and the solution was changed every 6 h.The effects of limb storage were evaluated by weight gain,perfusate biochemical analysis,enzyme-linked immunosorbent assay,and histological analysis.All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance.The p value of less than 0.05 was considered to indicate statistical significance.Results:In the NMP group,the weight gained percentage was 11.72%±4.06%;the hypoxia-inducible factor-1αcontents showed no significant changes;the shape of muscle fibers was normal;the gap between muscle fibers slightly increased,showing the intercellular distance of(30.19±2.83)μm;and the vascularα-smooth muscle actin(α-SMA)contents were lower than those in the normal blood vessels.The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion,decreased after each perfusate change,and remained stable at the end of perfusion showing a peak level of 4097.6 U/L.The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L.In the SCS group,the percentage of weight gain was 0.18%±0.10%,and the contents of hypoxia-inducible factor-1αincreased gradually and reached the maximum level of(164.85±20.75)pg/mL at the end of the experiment.The muscle fibers lost their normal shape and the gap between muscle fibers increased,showing an intercellular distance of(41.66±5.38)μm.The contents of vascularα-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions:NMP caused lesser muscle damage and contained more vascularα-SMA as compared to SCS.This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.
