Department of Preclinical Evaluation, Pre-Clinical Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Department of Medical Engineering and Cardiology, Pre-Clinical Research Center, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
J Artif Organs. 2021 Jun;24(2):111-119. doi: 10.1007/s10047-020-01219-3. Epub 2021 Feb 9.
Chronic blood trauma caused by the shear stresses generated by mechanical circulatory support (MCS) systems is one of the major concerns to be considered during the development of ventricular assist devices. Large multimers with high-molecular-weight von Willebrand factor (VWF) are extended by the fluid forces in a shear flow and are cleaved by ADAMTS13. Since the mechanical revolving motions in artificial MCSs induce cleavage in large VWF multimers, nonsurgical bleeding associated with the MCS is likely to occur after mechanical hemodynamic support. In this study, the shear stress (~ 600 Pa) and exposure time related to hemolysis and VWF degradation were investigated using a newly designed mechanical shuttle shear flow tester. The device consisted of a pair of cylinders facing the test section of a small-sized pipe; both the cylinders were connected to composite mechanical heads with a sliding-sleeve structure for axial separation during the withdrawing motion. The influence of exposure time, in terms of the number of stress cycles, on hemolysis and VWF degradation was confirmed using fresh goat blood, and the differences in the rates of dissipation of the multimers were established. The plasma-free hemoglobin levels showed a logarithmic increase corresponding to the number of cycles, and the dissipation of large VWF multimers occurred within a few seconds under high shear stress flow conditions.
慢性血液创伤是由机械循环支持(MCS)系统产生的切应力引起的,这是在开发心室辅助设备时需要考虑的主要问题之一。在切变流中,高分子量 von Willebrand 因子(VWF)的大多聚体被流体力拉伸,并被 ADAMTS13 切割。由于人工 MCS 中的机械旋转运动导致大 VWF 多聚体的切割,因此在机械血流动力学支持后,可能会发生与 MCS 相关的非手术性出血。在这项研究中,使用新设计的机械穿梭剪切流测试器研究了与溶血和 VWF 降解相关的剪切应力(~600 Pa)和暴露时间。该装置由一对面对小管测试段的圆柱体组成;两个圆柱体都与带有滑动套筒结构的复合机械头相连,在缩回运动过程中可实现轴向分离。使用新鲜山羊血确认了暴露时间(以应力循环次数计)对溶血和 VWF 降解的影响,并确定了多聚体消散率的差异。血浆游离血红蛋白水平呈对数增加,与循环次数相对应,并且在高剪切应力流条件下,大 VWF 多聚体在几秒钟内消散。