Rikhtegar Farhad, Edelman Elazer R, Olgac Ufuk, Poulikakos Dimos, Kurtcuoglu Vartan
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
J Control Release. 2016 Sep 28;238:1-9. doi: 10.1016/j.jconrel.2016.07.023. Epub 2016 Jul 16.
Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively high. Further optimization of drug release is required to minimize thrombosis risk while maintaining therapeutic dose. The complex three-dimensional geometry of deployed stents together with the combination of diffusive and advective drug transport render an intuitive understanding of the situation exceedingly difficult. In situations such as this, computational modeling has proven essential, helping define the limits of efficacy, determine the mode and mechanism of drug release, and identify alternatives to avoid toxicity. A particularly challenging conformation is encountered in coronary arteries with overlapping stents. To study hemodynamics and drug deposition in such vessels we combined high-resolution, multi-scale ex vivo computed tomography with a flow and mass transfer computational model. This approach ensures high geometric fidelity and precise, simultaneous calculation of blood flow velocity, shear stress and drug distribution. Our calculations show that drug uptake by the arterial tissue is dependent both on the patterns of flow disruption near the wall, as well as on the relative positioning of drug-eluting struts. Overlapping stent struts lead to localized peaks of drug concentration that may increase the risk of thrombosis. Such peaks could be avoided by anisotropic stent structure or asymmetric drug release designed to yield homogeneous drug distribution along the coronary artery and, at the least, suggest that these issues need to remain in the forefront of consideration in clinical practice.
药物洗脱支架已被公认为主流的血管内治疗方法,但其安全性问题可能未得到充分重视。虽然再狭窄导致的失败率已降至5%以下,但支架血栓形成的风险及相关死亡率仍然相对较高。需要进一步优化药物释放,以在维持治疗剂量的同时将血栓形成风险降至最低。已部署支架复杂的三维几何形状,加上扩散和对流药物传输的结合,使得直观理解这种情况极其困难。在这种情况下,计算建模已证明至关重要,有助于界定疗效极限、确定药物释放的方式和机制,并识别避免毒性的替代方法。在有重叠支架的冠状动脉中会遇到一种特别具有挑战性的构象。为了研究此类血管中的血流动力学和药物沉积情况,我们将高分辨率、多尺度的离体计算机断层扫描与流动和传质计算模型相结合。这种方法确保了高几何保真度,并能精确、同时计算血流速度、剪切应力和药物分布。我们的计算表明,动脉组织对药物的摄取既取决于靠近血管壁处的血流紊乱模式,也取决于药物洗脱支柱的相对位置。重叠的支架支柱会导致药物浓度出现局部峰值,这可能会增加血栓形成的风险。通过各向异性支架结构或旨在沿冠状动脉产生均匀药物分布的不对称药物释放可以避免此类峰值,至少这表明这些问题在临床实践中仍需作为首要考虑因素。