Sheriff Jawaad, Girdhar Gaurav, Chiu Wei-Che, Jesty Jolyon, Slepian Marvin J, Bluestein Danny
Department of Biomedical Engineering, Stony Brook University, T15-090 Health Sciences Center, Stony Brook, NY, 11794-8151, USA.
J Thromb Thrombolysis. 2014 May;37(4):499-506. doi: 10.1007/s11239-013-0997-6.
Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term antiplatelet and anticoagulant therapy. While several studies have examined the effectiveness of one such agent, aspirin, under flow conditions, data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston, TX, USA): (a) 20 μM aspirin was added exogenously in vitro to platelets isolated from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to untreated controls. Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shear-induced platelet activation in the VAD. Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy, as well as for testing the thrombogenic performance of devices during their research and development.
心室辅助装置（VADs）被植入终末期心力衰竭患者体内，以提供短期和长期的血流动力学支持。不幸的是，由于这些装置内产生的严重紊乱的动态血流状况，出血和血栓栓塞并发症需要复杂的长期抗血小板和抗凝治疗。虽然有几项研究考察了一种此类药物阿司匹林在血流条件下的有效性，但缺乏比较体外和体内代谢阿司匹林疗效的数据。在含有德巴基VAD（美国得克萨斯州休斯顿市MicroMed心血管公司）的血流回路中，用纯化的人血小板进行了两组体外研究，血小板在其中循环30分钟：（a）将20μM阿司匹林体外添加到从无阿司匹林受试者分离的血小板中，（b）在摄入1000mg阿司匹林后2小时（n = 14）和20小时（n = 13）从供体获取血小板。用改良的基于凝血酶原酶的测定法测量近实时血小板活化状态（PAS）。与未处理的对照相比，体外和体内（代谢）暴露于阿司匹林的血小板的血小板活化率分别降低了28.2%和25.3%。我们的结果表明，在测试VAD中减少剪切诱导的血小板活化的效果时，用阿司匹林等抗血小板药物进行体外治疗与体内代谢的阿司匹林一样有效。使用PAS测定法为抗血小板功效的体内测试提供了一种实用的体外替代方法，也为在装置研发过程中测试其血栓形成性能提供了替代方法。
