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高剪切力下红细胞穿过机械心脏瓣膜狭缝的动力学。

The dynamics of red blood cells traversing slits of mechanical heart valves under high shear.

机构信息

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, China.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, China.

出版信息

Biophys J. 2024 Nov 5;123(21):3780-3797. doi: 10.1016/j.bpj.2024.09.027. Epub 2024 Sep 26.

Abstract

Hemolysis, including subclinical hemolysis, is a potentially severe complications of mechanical heart valves (MHVs), which leads to shortened red blood cell (RBC) lifespan and hemolytic anemia. Serious hemolysis is usually associated with structural deterioration and regurgitation. However, the shear stress in MHVs' narrow leakage slits is much lower than the shear stress threshold causing hemolysis and the mechanisms in this context remain largely unclear. This study investigated the hemolysis mechanism of RBCs in cell-size slits under high shear rates by establishing in vitro microfluidic devices and a coarse-grained molecular dynamics (CGMD) model, considering both fluid and structural effects simultaneously. Microfluidic experiments and computational simulation revealed six distinct dynamic states of RBC traversal through MHVs' microscale slits under various shear rates and slit sizes. It elucidated that RBC dynamic states were influenced by not only by fluid forces but significantly by the compressive force of slit walls. The variation of the potential energy of the cell membrane indicated its stretching, deformation, and rupture during traversal, corresponding to the six dynamic states. The maximum forces exerted on membrane by water particles and slit walls directly determined membrane rupture, serving as a critical determinant. This analysis helps in understanding the contribution of the slit walls to membrane rupture and identifying the threshold force that leads to membrane rupture. The hemolysis mechanism of traversing microscale slits is revealed to effectively explain the occurrences of hemolysis and subclinical hemolysis.

摘要

溶血,包括亚临床溶血,是机械心脏瓣膜(MHV)的一种潜在严重并发症,导致红细胞(RBC)寿命缩短和溶血性贫血。严重溶血通常与结构恶化和反流有关。然而,MHV 狭窄泄漏狭缝中的切应力远低于导致溶血的切应力阈值,并且这方面的机制在很大程度上仍不清楚。本研究通过建立体外微流控装置和粗粒分子动力学(CGMD)模型,同时考虑流体和结构效应,研究了高剪切率下 RBC 在细胞尺寸狭缝中的溶血机制。微流控实验和计算模拟揭示了在不同剪切率和狭缝尺寸下,RBC 通过 MHV 微尺度狭缝的六种不同的动态状态。结果表明,RBC 的动态状态不仅受流体力的影响,而且还受到狭缝壁的压缩力的显著影响。细胞膜势能的变化表明其在穿越过程中的拉伸、变形和破裂,与这六种动态状态相对应。水分子和狭缝壁对细胞膜施加的最大力直接决定了细胞膜的破裂,这是一个关键决定因素。这种分析有助于了解狭缝壁对细胞膜破裂的贡献,并确定导致细胞膜破裂的临界力。穿过微尺度狭缝的溶血机制有效地解释了溶血和亚临床溶血的发生。

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