High Shear Thrombus Formation under Pulsatile and Steady Flow
High Shear Thrombus Formation under Pulsatile and Steady Flow
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DOI：
10.1007/s13239-014-0180-z
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发表时间：
2014-06-01
影响因子：
1.8
通讯作者：
Ku, David N.
中科院分区：
文献类型：
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作者：
Casa, Lauren D. C.;Ku, David N.
以前的大多数研究都是在生理剪切率下的稳定流动条件下研究血栓的体外形成，但在高剪切率和脉动流的情况下，闭塞性血栓会导致心肌梗死和卒中。两份关于脉动血流治疗血栓形成的报告产生了相互矛盾的结果。在目前的研究中，我们量化了与冠状动脉血栓形成相关的非常高的切变、反向脉动血流对导致闭塞性血栓形成的血小板沉积的影响。在脉动或稳定流动下，将猪全血灌流到胶原蛋白涂层的管状狭窄试验段中。产生脉动血流的频率为每分钟60次，并有类似冠状动脉波形的大幅度漂移。或者，来自压力驱动系统的稳定流动条件产生与脉动系统的最大(16000 S(-1))、平均(3800 S(-1))和中等(6500 S(-1))相匹配的剪切率。使用连接在显微镜上的高分辨率电荷耦合器件记录血栓厚度的增长。在大多数情况下，定常流动再现了搏动性流动血栓的形成。平均剪切率匹配的脉动流和稳态流的滞留时间t(LAG)、血栓生长率、dv/dt和闭塞时间t(OCC)无统计学差异。脉动流动条件下的t(OCC)=5.5+/-2.8min，与t(OCC)=6.2+/-1.7min的稳态平均剪切速率条件下的t(OCC)没有显著差异。同样，稳定的中等剪切率和稳定的最大剪切率条件下的咬合时间与脉动流条件下分别产生4.6+/-2.9分钟和4.6+/-1.8分钟的TOCC没有显著差异。与脉动流(t(滞后)=42.7 S，p=0.0 3)、恒定平均流(t(滞后)=60.9 S，p=0.0 2)和恒定中间流(t(滞后)=39.9 S，p=0.0 1)相比，恒定流在最大剪切率为16000时的滞后时间缩短至2 6.1 S。高剪切、脉动条件下的闭塞性血栓形成可以在体外用恒定流动和与闭塞时间、滞后时间和生长速率相匹配的平均剪切率来模拟。我们的结果表明，对于一个动脉频率，切变率的大小对血栓生长特性的影响比血流搏动性更大。
Most previous studies have investigated in vitro thrombus formation under steady flow conditions at physiological shear rates, though occlusive thrombosis leading to myocardial infarction and stroke forms under elevated shear rates and pulsatile flow. Two reports of pulsatile flow on thrombosis have yielded conflicting results. In the present study, we quantify the effect of very high shear, reversing pulsatile flow relevant to coronary thrombosis on platelet deposition leading to occlusive thrombus formation. Whole porcine blood was perfused in a collagen-coated, tubular, stenotic test section under pulsatile or steady flow. Pulsatile flow was generated with a frequency of 60 beats per minute and large magnitude excursions similar to a coronary artery waveform. Alternatively, steady flow conditions from a pressure driven system created shear rates matched to the maximum (16000 s(-1)), mean (3800 s(-1)), and an intermediate (6500 s(-1)) shear rates corresponding to the pulsatile system. Thrombus growth in thickness was recorded using a high-resolution CCD attached to a microscope. Steady flow recreated pulsatile flow thrombus formation in most cases. Lag time, t(lag), thrombus growth rate, dV/dt, and time to occlusion, t(occ), did not show statistically significant differences between pulsatile flow and steady flow with matched mean shear rate. Pulsatile flow conditions yielded t(occ) = 5.5 +/- 2.8 min, which was not significantly different compared to a steady mean shear rate condition with t(occ) = 6.2 +/- 1.7 min. Similarly, occlusion times for steady intermediate and steady maximum shear rate conditions were not significantly difference from pulsatile flow conditions yielding tocc of 4.6 +/- 2.9 and 4.6 +/- 1.8 min, respectively. In contrast, lag time for steady flow at maximum shear rate of 16000 s(-1) was decreased to 26.1 s compared to pulsatile flow (t(lag) = 42.7 s, p = 0.03), steady mean flow (t(lag) = 60.9 s, p = 0.02), and steady intermediate flow (t(lag) = 39.9 s, p = 0.01). Occlusive thrombus formation under high shear, pulsatile conditions may be modeled in vitro using steady flow with matched mean shear rate with respect to occlusion time, lag time, and growth rate. Our results indicate that the magnitude of shear rate more strongly affects thrombus growth characteristics than flow pulsatility for an arterial frequency.