Fabrication and in vivo thrombogenicity testing of nitric oxide generating artificial lungs.

Fabrication and in vivo thrombogenicity testing of nitric oxide generating artificial lungs.
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DOI:
10.1002/jbm.a.34655
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发表时间:
2013-12
影响因子:
4.9
通讯作者:
Cook, Keith E.
Cook, Keith E.
中科院分区:
工程技术3区
文献类型:
--
作者:
Amoako, Kagya A.;Montoya, Patrick J.;Major, Terry C.;Suhaib, Ahmed B.;Handa, Hitesh;Brant, David O.;Meyerhoff, Mark E.;Bartlett, Robert H.;Cook, Keith E.

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中空纤维人工肺越来越多地用于长期应用。然而,凝块形成限制了它们的使用1-2周。本研究探讨了一氧化氮生成(NOgen)中空纤维对人工肺血栓形成的影响。制造有机硅中空纤维以并入50 nm铜颗粒作为从血液产生NO的催化剂。将具有和不具有(对照)这些颗粒的纤维结合到具有0.1 m2表面积的人工肺中,并插入用NOgen材料尖端对尖端涂覆的回路中。将回路(N=5/每只)以无泵动静脉配置连接至家兔,并在350- 400 s的活化凝血时间下运行4 h。三个控制回路完全凝结,而没有一个NOgen回路失效。因此,与对照组(35.2 ± 19.7)(ml/min)相比,NOgen组(95.9 ± 11.7,p < 0.01)的血流量显著更高,并且4小时后对照组(15.38 ± 9.65,p<0.001)的阻力显著高于NOgen组(0.09 ± 0.03)(mmHg/mL/min)。另一方面,对照组血小板计数和血浆纤维蛋白原浓度(以基线百分比表示)(63.7 ± 5.7%,77.2 ± 5.6% [p<0.05])高于NOgen组(60.4 ± 5.1%,63.2 ± 3.7%)。NOgen组的血浆铜水平在4小时时为基线的2.8倍(132.8 ± 4.5 μg/dl),而对照组无变化。这项工作表明,NO生成气体交换纤维可能是一种潜在的有效方式来控制人工肺内的凝血。
Hollow fiber artificial lungs are increasingly being used for long-term applications. However, clot formation limits their use to 1-2 weeks. This study investigated the effect of nitric oxide generating (NOgen) hollow fibers on artificial lung thrombogenicity. Silicone hollow fibers were fabricated to incorporate 50 nm copper particles as a catalyst for NO generation from the blood. Fibers with and without (control) these particles were incorporated into artificial lungs with a 0.1 m2 surface area and inserted in circuits coated tip-to-tip with the NOgen material. Circuits (N=5/each) were attached to rabbits in a pumpless, arterio-venous configuration and run for 4 hrs at an activated clotting time of 350-400s. Three control circuits clotted completely, while none of the NOgen circuits failed. Accordingly, blood flows were significantly higher in the NOgen group (95.9 ± 11.7, p < 0.01) compared to the controls (35.2 ± 19.7) (ml/min), and resistance was significantly higher in the control group after 4 hours (15.38 ± 9.65, p<0.001) than in NOgen (0.09 ± 0.03) (mmHg/mL/min). On the other hand, platelet counts and plasma fibrinogen concentration expressed as percent of baseline in control group (63.7 ± 5.7%, 77.2 ± 5.6% [p<0.05]) were greater than those in the NOgen group (60.4 ± 5.1%, 63.2 ± 3.7%). Plasma copper levels in the NOgen group were 2.8 times baseline at 4 hours (132.8 ± 4.5 μg/dl) and unchanged in the controls. This work demonstrates that NO generating gas exchange fibers could be a potentially effective way to control coagulation inside artificial lungs.
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