Department of Biomedical Engineering, T18-030 Health Sciences Center, Stony Brook University, Stony Brook, NY 11794-8181, USA.
Ann Biomed Eng. 2010 Apr;38(4):1442-50. doi: 10.1007/s10439-010-9936-2. Epub 2010 Feb 5.
Individuals with mechanical heart valve implants are plagued by flow-induced thromboembolic complications, which are undoubtedly caused by platelet activation. Flow fields in or around the affected regions involve brief exposure to pathologically high-shear stresses on the order of 100 to 1000 dyne/cm(2). Although high shear is known to activate platelets directly, their subsequent behavior is not known. We hypothesize that the post-high-shear activation behavior of platelets is particularly relevant in understanding the increased thrombotic risk associated with blood-recirculating prosthetic cardiovascular devices. Purified platelets were exposed to brief (5-40 s) periods of high-shear stress, and then exposed to longer periods (15-60 min) of low shear. Their activation state was measured using a prothrombinase-based assay. Platelets briefly exposed to an initial high-shear stress (e.g., 60 dyne/cm(2) for 40 s) activate a little, but this study shows that they are now sensitized, and when exposed to subsequent low shear stress, they activate at least 20-fold faster than platelets not initially exposed to high shear. The results show that platelets in vitro exposed beyond a threshold of high-shear stress are primed for subsequent activation under normal cardiovascular circulation conditions, and they do not recover from the initial high-shear insult.
患有机械心脏瓣膜植入物的个体经常受到血流诱导的血栓栓塞并发症的困扰，而这些并发症无疑是由血小板激活引起的。受影响区域内或周围的流场会短暂暴露于病理高剪切应力下，其量级为 100 至 1000 达因/平方厘米。虽然已知高剪切会直接激活血小板，但随后的血小板行为尚不清楚。我们假设血小板在高剪切后的激活行为对于理解与血液再循环的人工心血管设备相关的增加的血栓形成风险特别重要。将纯化的血小板暴露于短暂的（5-40 秒）高剪切应力下，然后暴露于更长时间（15-60 分钟）的低剪切应力下。使用基于凝血酶原酶的测定法测量它们的激活状态。短暂暴露于初始高剪切应力（例如，60 达因/平方厘米持续 40 秒）的血小板仅轻度激活，但本研究表明，它们现在已被致敏，当暴露于随后的低剪切应力时，它们的激活速度比未最初暴露于高剪切的血小板至少快 20 倍。结果表明，体外暴露于高剪切应力阈值以上的血小板已为随后在正常心血管循环条件下的激活做好准备，并且它们不会从初始的高剪切损伤中恢复。
