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 h-circulation. 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.
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机译:本研究开发了一种新型的吸附剂,固定有1-丝氨酸配体(PVDF-Ser)的聚偏二氟乙烯基质,以评估其通过体外血液灌流在化脓猪中的安全性和治疗效果。首先在体外测量吸附剂的内毒素吸附效率(EAE)。然后评估体外循环过程中的生物相容性和血液动力学变化。在1小时内静脉内接受脂多糖(大肠杆菌O111:B4,5μg/ kg)的16只猪中,有一半用新的吸附剂进行血液灌流连续治疗2小时。分析了循环内毒素和某些细胞因子的变化以及呼吸功能。最终评估了72小时生存率。循环2小时后,EAE达到46.3%(在80 ml小牛血清中为100 EU / ml)。在该过程中未观察到有害作用。血液灌流过程中血浆内毒素,白介素6(IL-6)和肿瘤坏死因子-α(TNF-α)水平降低。在此过程中和之后,动脉氧合也得到改善。此外,生存时间显着延长(中位生存时间> 72小时,而中值生存时间为47.5小时)。新型产品PVDF-Ser具有较高的安全性和有效性,可吸附内毒素。尽早使用新的吸附剂进行体外血液灌流可以降低循环内毒素,IL-6和TNF-α的水平,此外还可以改善败血症猪的呼吸功能和72小时存活率。使用新型吸附器进行血液净化的内毒素去除策略为脓毒症治疗提供了潜在的有希望的未来。
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