Bosch T, Schmidt B, Blumenstein M, Gurland H J
Nephrological Department, Klinikum Grosshadern, University of Munich, Germany.
Artif Organs. 1993 Jul;17(7):640-52. doi: 10.1111/j.1525-1594.1993.tb00609.x.
To date, selective extracorporeal low-density lipoprotein (LDL) removal can only be performed from plasma; that is, a plasma-cell separation step using a centrifuge or a plasma membrane separator is necessary initially. This article characterizes a new polyacrylate-based LDL adsorber directly applicable to whole blood. In vitro single-pass hemoperfusion tests using pooled donor blood showed quantitative adsorption of atherogenic LDL-cholesterol (LDL-C) and complete recovery of protective high-density lipoprotein C. Fibrinogen, another independent risk factor of atherosclerosis, was also adsorbed to a lesser extent. Single-pass ex vivo biocompatibility using fresh donor blood on-line was excellent and resulted in minimal cell loss. Neither signs of hemolysis nor activation of monocytes (interleukin-1 production) were detected. Only slight activation of leukocytes (elastase release) and thrombocytes (platelet factor 4 secretion) as well as of coagulation (thrombin-antithrombin complex formation) and complement (C3a, C5a generation) was observed. Under the experimental conditions used, the optimal anticoagulation regimen was 0.5 IU heparin plus 0.375 mg citrate/ml blood. Priming the column with a buffer of pH 7.4 containing heparin, citrate, and Ca2+ is recommended. In conclusion, this new adsorber exhibited selective LDL-C adsorption in vitro combined with excellent ex vivo biocompatibility and thus holds great promise for a successful clinical application in a closed-loop system in patients.
迄今为止,选择性体外低密度脂蛋白(LDL)去除仅能从血浆中进行;也就是说,最初需要使用离心机或血浆膜分离器进行血浆-细胞分离步骤。本文描述了一种直接适用于全血的新型聚丙烯酸酯基LDL吸附剂。使用汇集的供血者血液进行的体外单通道血液灌注试验显示,致动脉粥样硬化的LDL胆固醇(LDL-C)被定量吸附,而具有保护作用的高密度脂蛋白C完全回收。纤维蛋白原是动脉粥样硬化的另一个独立危险因素,其吸附程度也较低。使用新鲜供血者血液进行的在线单通道离体生物相容性极佳,细胞损失极少。未检测到溶血迹象或单核细胞激活(白细胞介素-1产生)。仅观察到白细胞(弹性蛋白酶释放)、血小板(血小板因子4分泌)以及凝血(凝血酶-抗凝血酶复合物形成)和补体(C3a、C5a生成)有轻微激活。在所使用的实验条件下,最佳抗凝方案为每毫升血液0.5国际单位肝素加0.375毫克柠檬酸盐。建议用含有肝素、柠檬酸盐和Ca2+的pH 7.4缓冲液对柱进行预充。总之,这种新型吸附剂在体外表现出选择性LDL-C吸附,并具有出色的离体生物相容性,因此在患者闭环系统中成功临床应用具有很大前景。