Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA.
Ying Wu College of Computing Sciences, Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, 07102, USA.
Comput Biol Med. 2019 Mar;106:1-11. doi: 10.1016/j.compbiomed.2019.01.001. Epub 2019 Jan 11.
Ischemia which leads to heart attacks and strokes is one of the major causes of death in the world. Whether an occlusion occurs or not depends on the ability of a growing thrombus to resist flow forces exerted on its structure. This manuscript provides the first known in vivo measurement of how much stress a clot can withstand, before yielding to the surrounding blood flow. Namely, Lattice-Boltzmann Method flow simulations are performed based on 3D clot geometries, which are estimated from intravital microscopy images of laser-induced injuries in cremaster microvasculature of live mice. In addition to reporting the blood clot yield stresses, we also show that the thrombus "core" does not experience significant deformation, while its "shell" does. This indicates that the shell is more prone to embolization. Therefore, drugs should be designed to target the shell selectively, while leaving the core intact to minimize excessive bleeding. Finally, we laid down a foundation for a nondimensionalization procedure which unraveled a relationship between clot mechanics and biology. Hence, the proposed framework could ultimately lead to a unified theory of thrombogenesis, capable of explaining all clotting events. Thus, the findings presented herein will be beneficial to the understanding and treatment of heart attacks, strokes and hemophilia.
导致心脏病发作和中风的缺血是世界上主要的死亡原因之一。是否发生闭塞取决于正在生长的血栓抵抗作用于其结构的流动力的能力。本文提供了第一个已知的体内测量方法，即在屈服于周围血流之前，血栓可以承受多少压力。具体来说，根据活体小鼠隐静脉微血管内激光诱导损伤的活体显微镜图像，对 3D 血栓几何形状进行了格子玻尔兹曼方法流动模拟。除了报告血栓屈服应力外，我们还表明血栓的“核心”不会经历明显的变形，而其“外壳”会。这表明外壳更容易栓塞。因此，应该设计药物有选择地靶向外壳，同时保持核心完整，以尽量减少过度出血。最后，我们为无量纲化过程奠定了基础，该过程揭示了血栓力学和生物学之间的关系。因此，所提出的框架最终可能导致血栓形成的统一理论，能够解释所有的凝血事件。因此，本文的研究结果将有助于理解和治疗心脏病发作、中风和血友病。
