A novel adsorber,polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser),was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfu...A novel adsorber,polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser),was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfusion.Endotoxin adsorption efficiency (EAE) of the adsorber was firstly measured in vitro.The biocompatibility and hemodynamic changes during extracorporeal circulation were then evaluated.One half of 16 pigs receiving lipopolysaccharide (Escherichia coli O111:B4,5 μg/kg) intravenously in 1 h were consecutively treated by hemoperfusion with the new adsorber for 2 h.The changes of circulating endotoxin and certain cytokines and respiratory function were analyzed.The 72 h-survival rate was assessed eventually.EAE reached 46.3% (100 EU/ml in 80 ml calf serum) after 2 hcirculation.No deleterious effect was observed within the process.The plasma endotoxin,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) levels were decreased during the hemoperfusion.Arterial oxygenation was also improved during and after the process.Furthermore,the survival time was significantly extended (>72 h vs.47.5 h for median survival time).The novel product PVDF-Ser could adsorb endotoxin with high safety and efficacy.Early use of extracorporeal hemoperfusion with the new adsorber could reduce the levels of circulating endotoxin,IL-6,and TNF-α,besides improve respiratory function and consequent 72 h-survival rate of the septic pigs.Endotoxin removal strategy with blood purification using the new adsorber renders a potential promising future in sepsis therapy.展开更多
文摘目的研究应用聚偏氟乙烯(polyvinylidene difluoride,PVDF)-丝氨酸(serine,Ser)吸附膜血液灌流对感染性休克氧化应激和器官功能的影响。方法雄性家猪16头,给予内毒素(lipopolysaccharides,LPS)1μg/kg.h)静脉泵入4 h复制感染性休克模型。随机分为实验组(E组),应用PVDF-Ser吸附膜进行血液灌流2 h;对照组(C组),应用空白灌流器进行血液灌流2 h。于基础期、注射内毒素后和血液灌流后分别测定血浆内毒素浓度、血浆异前列腺素F2(F2-Isoprostane)、血浆硫氧还蛋白(thioredoxin,TRX)和尿液8-羟基-2’-脱氧鸟苷(8-hydroxy-2’-deoxyguanosine,8-OHdG)水平,测定肝肾功能、心肌酶、凝血指标、左心室收缩力指数(index of left ventricular contractility,dPmax)和血管外肺水指数(index of extra-vascular lung water,EVLWI)、动脉血氧分压(arterial partial pressure of oxygen,PaO2);实验结束后测定肺、肝组织还原型谷胱甘肽(glutathione,GSH)含量与髓过氧化物酶(myeloperoxidase,MPO)活力。结果血液灌流后E组F2-Isoprostane、TRX和尿8-OHdG显著低于C组,分别为[(125±54)pg/ml vs(446±101)pg/ml,P=0.004]、[(129±49)ng/ml vs(247±117)ng/ml,P=0.037]、[(10.5±7.3)ng/(mg.Scr)vs(31.1±8.7)ng/(mg.Scr),P=0.016];E组的器官功能指标较C组显著改善;肝、肺组织的GSH含量和MPO活力,组间比较亦存在统计学差异(P<0.05)。结论应用PVDF-Ser吸附膜进行血液灌流,显著减轻感染性休克的氧化应激,从而保护重要器官功能。
基金Project (No.2007C33008) supported by the Key Scientific and Technological Project of Science and Technology Department of Zhejiang Province,China
文摘A novel adsorber,polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser),was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfusion.Endotoxin adsorption efficiency (EAE) of the adsorber was firstly measured in vitro.The biocompatibility and hemodynamic changes during extracorporeal circulation were then evaluated.One half of 16 pigs receiving lipopolysaccharide (Escherichia coli O111:B4,5 μg/kg) intravenously in 1 h were consecutively treated by hemoperfusion with the new adsorber for 2 h.The changes of circulating endotoxin and certain cytokines and respiratory function were analyzed.The 72 h-survival rate was assessed eventually.EAE reached 46.3% (100 EU/ml in 80 ml calf serum) after 2 hcirculation.No deleterious effect was observed within the process.The plasma endotoxin,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) levels were decreased during the hemoperfusion.Arterial oxygenation was also improved during and after the process.Furthermore,the survival time was significantly extended (>72 h vs.47.5 h for median survival time).The novel product PVDF-Ser could adsorb endotoxin with high safety and efficacy.Early use of extracorporeal hemoperfusion with the new adsorber could reduce the levels of circulating endotoxin,IL-6,and TNF-α,besides improve respiratory function and consequent 72 h-survival rate of the septic pigs.Endotoxin removal strategy with blood purification using the new adsorber renders a potential promising future in sepsis therapy.
