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.

中文翻译：

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高剪切作用下红细胞穿过机械心脏瓣膜狭缝的动力学


溶血，包括亚临床溶血，是机械心脏瓣膜 （MHV） 的潜在严重并发症，可导致红细胞 （RBC） 寿命缩短和溶血性贫血。严重的溶血通常与结构恶化和反流有关。然而，MHV 狭窄泄漏狭缝中的剪切应力远低于导致溶血的剪切应力阈值，在这种情况下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，研究了高剪切速率下细胞大小狭缝中红细胞的溶血机制。微流体实验和计算模拟揭示了在不同剪切速率和狭缝大小下，RBC 穿过 MHV 微尺度狭缝的六种不同的动态状态。它阐明了 RBC 动态状态不仅受流体力的影响，还显着受狭缝壁的压缩力的影响。细胞膜势能的变化表明了细胞膜在遍历过程中的拉伸、变形和破裂，对应于 6 种动态状态。水颗粒和狭缝壁施加在膜上的最大力直接决定了膜破裂，是一个关键的决定因素。该分析有助于了解狭缝壁对膜破裂的贡献，并确定导致膜破裂的阈值力。揭示了穿越微尺度狭缝的溶血机制，以有效解释溶血和亚临床溶血的发生。