Ex vivo evaluation of a Taylor-Couette flow, immobilized heparinase I device for clinical application.
Ex vivo evaluation of a Taylor-Couette flow, immobilized heparinase I device for clinical application.
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DOI：
10.1073/pnas.96.5.2350
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发表时间：
1999-03
影响因子：
11.1
通讯作者：
G. Ameer;G. Barabino;R. Sasisekharan;W. Harmon;C. Cooney;R. Langer
中科院分区：
文献类型：
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作者：
G. Ameer;G. Barabino;R. Sasisekharan;W. Harmon;C. Cooney;R. Langer
有效和安全的肝素抗凝仍然是急性肾功能衰竭患者连续性肾脏替代治疗和间歇性血液透析的一个问题。为了使肝素治疗对出血风险高的急性肾功能衰竭患者更安全，我们建议通过固定肝素酶I过滤器对回路进行局部肝素化。本研究在绵羊模型中测试了基于Taylor-Couette流和同时分离/反应的装置去除肝素的有效性和安全性。通过溴化氰活化将肝素酶I固定在琼脂糖珠上。该装置被称为涡流血浆置换反应器，由两个同心圆筒、45 ml的预充体积、用于血浆分离的微孔膜和外部隔室组成，在外部隔室中，固定化肝素酶I与血细胞分开流化。进行手动白色细胞和血小板计数、红细胞压积、总蛋白和纤维蛋白原测定。通过全血凝固时间（WBRT）间接测量肝素水平。涡流血浆置换反应器在体外循环回路中维持的肝素水平显著高于绵羊（器械入口WBRT为1。5倍于器械出口WBRT），无溶血。在长达2小时的操作中，反应器处理不会影响全血细胞计数、血小板和蛋白质水平的任何生理学显著变化。此外，肉眼尸检和组织病理学未显示肾脏、肝脏、心脏、大脑和脾脏的任何显著异常。
Efficient and safe heparin anticoagulation has remained a problem for continuous renal replacement therapies and intermittent hemodialysis for patients with acute renal failure. To make heparin therapy safer for the patient with acute renal failure at high risk of bleeding, we have proposed regional heparinization of the circuit via an immobilized heparinase I filter. This study tested a device based on Taylor-Couette flow and simultaneous separation/reaction for efficacy and safety of heparin removal in a sheep model. Heparinase I was immobilized onto agarose beads via cyanogen bromide activation. The device, referred to as a vortex flow plasmapheretic reactor, consisted of two concentric cylinders, a priming volume of 45 ml, a microporous membrane for plasma separation, and an outer compartment where the immobilized heparinase I was fluidized separately from the blood cells. Manual white cell and platelet counts, hematocrit, total protein, and fibrinogen assays were performed. Heparin levels were indirectly measured via whole-blood recalcification times (WBRTs). The vortex flow plasmapheretic reactor maintained significantly higher heparin levels in the extracorporeal circuit than in the sheep (device inlet WBRTs were 1. 5 times the device outlet WBRTs) with no hemolysis. The reactor treatment did not effect any physiologically significant changes in complete blood cell counts, platelets, and protein levels for up to 2 hr of operation. Furthermore, gross necropsy and histopathology did not show any significant abnormalities in the kidney, liver, heart, brain, and spleen.