Thrombus causes fluctuations in arterial drug delivery from intravascular stents.
Thrombus causes fluctuations in arterial drug delivery from intravascular stents.
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DOI：
10.1016/j.jconrel.2008.07.027
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发表时间：
2008-11-12
影响因子：
10.8
通讯作者：
Edelman, Elazer R.
中科院分区：
文献类型：
--
作者：
Balakrishnan, Brinda;Dooley, John;Kopia, Gregory;Edelman, Elazer R.
动脉药物浓度决定局部毒性。因此，围绕药物洗脱支架的紧急安全性问题要求研究导致动脉药物摄取波动的因素。将药物洗脱支架植入猪冠状动脉，采用二维计算药物转运模型跟踪动脉药物摄取。动脉药物摄取在体内发生的速度比预测的自由药物扩散，因此，一个替代的，快速运输的机制，已提出涉及载体介导的运输。虽然有微小的变化，在体内释放动力学支架支架，动脉药物沉积变化高达114%，支架植入后两周。粘附附壁血栓的范围也在植入后3天内波动113%。计算药物转运模型预测，局灶性和弥漫性血栓通过减少药物洗脱，随后增加局部药物可用性，与血栓大小成比例地升高动脉药物沉积。动脉药物摄取的波动是常见的报告。我们现在解释，即使在支架药物释放范围很窄的情况下，可变的支架周围血栓也可以解释这种观察结果。附壁血栓对动脉药物沉积的影响可以通过强制缓慢、限速的动脉转运来规避，这种转运不能被附壁血栓进一步阻碍。
Arterial drug concentrations determine local toxicity. As such the emergent safety concerns surrounding drug-eluting stents mandate an investigation of the factors contributing to fluctuations in arterial drug uptake. Drug-eluting stents were implanted into porcine coronary arteries, arterial drug uptake was followed and modeled using 2-dimensional computational drug transport. Arterial drug uptake in vivo occurred faster than predicted by free drug diffusion, thus an alternate, mechanism for rapid transport has been proposed involving carrier-mediated transport. Though there was minimal variation in vivo in release kinetics from stent to stent, arterial drug deposition varied by up to 114% two weeks after stent implantation. The extent of adherent mural thrombus also fluctuated by 113% within 3 days after implantation. The computational drug transport model predicted that focal and diffuse thrombi elevate arterial drug deposition in proportion to the thrombus size by reducing drug washout subsequently increasing local drug availability. Fluctuations in arterial drug uptake are commonly reported. We now explain that variable peristrut thrombus can explain such observations even in the face of a narrow range of drug release from the stent. The mural thrombus effects on arterial drug deposition may be circumvented by forcing slow, rate limiting arterial transport that cannot be further hindered by mural thrombus.
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影响因子：
168.9
作者：
Daemen, Joost;Wenaweser, Peter;Serruys, Patrick W.
通讯作者：
Serruys, Patrick W.
影响因子：
20.1
作者：
Hwang, CW;Edelman, ER
通讯作者：
Edelman, ER
影响因子：
37.8
作者：
Farb, A;Heller, PF;Virmani, R
通讯作者：
Virmani, R
DOI：
10.1161/01.atv.4.3.283
发表时间：
1984-01-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
RAMIREZ, CA;COLTON, CK;LEES, RS
通讯作者：
LEES, RS
影响因子：
2.1
作者：
Ruef, Johannes;Kranzhofer, Roger
通讯作者：
Kranzhofer, Roger