Badimon Lina, Padro Teresa, Vilahur Gemma
Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Methods Mol Biol. 2012;788:43-57. doi: 10.1007/978-1-61779-307-3_4.
Platelet deposition, adhesion/aggregation, to the damaged vessel wall or atherosclerotic plaque components has shown to play a major role in hemostasis, thrombosis, and the development of atherosclerosis. Platelet-vessel wall interaction and thrombus formation is driven by blood flow rheology/hemodynamics (changes in local flow conditions), the nature of the flowing blood, and the characteristics of the triggering substrate (lesion type). An extracorporeal perfusion system (the Badimon chamber) was developed to investigate the dynamics of platelet deposition and thrombus formation on: (a) different surfaces (biological and synthetic); (b) under controlled blood flow conditions with varying degrees of stenosis mimicking various vascular conditions (patent and stenotic arteries); and (c) with varying perfusing blood treatments. In the following chapter, we thoroughly describe this experimental approach that has helped to improve the understanding of the pathophysiology of the acute coronary syndromes (Badimon et al., Arteriosclerosis 6:312-320, 1986; Badimon et al., J Lab Clin Med 110:706-718, 1987; Badimon et al., Blood 73:961-967, 1989; Mailhac et al., Circulation 90:988-996, 1994) and is a useful tool for the study and screening of new antithrombotic and platelet-inhibitory compounds (Badimon et al., Thromb Haemost 71:511-516, 1994; Vilahur et al., Circulation 110:1686-1693; Vilahur et al., Thromb Haemost 92:191-200, 2004; Vilahur et al., Cardiovasc Res 61:806-816; Vilahur et al., Thromb Haemost 98:662-669, 2007; Vilahur et al., Thromb Haemost 97:650-657, 2007; Zafar et al., J Thromb Haemost 5:1195-1200, 2007; Lev et al., J Am Coll Cardiol 43:966-971) and for the evaluation of the thrombogenicity associated to synthetic/prosthetic surfaces (Badimon et al., J Biomater Appl 5:27-48, 1990; Badimon et al., ASAIO Trans 33:621-625, 1987) and/or plasma components (cholesterol, glucose levels, etc.) (Badimon et al., Arterioscler Thromb 11:395-402, 1991; Osende et al., J Am Coll Cardiol 38:1307-1312; 2001).
血小板在受损血管壁或动脉粥样硬化斑块成分上的沉积、黏附/聚集,已被证明在止血、血栓形成以及动脉粥样硬化发展过程中起主要作用。血小板与血管壁的相互作用及血栓形成,由血流流变学/血液动力学(局部血流条件的变化)、流动血液的性质以及触发底物(病变类型)的特征所驱动。体外灌注系统(Badimon腔)被开发用于研究血小板在以下情况时的沉积动力学和血栓形成:(a)不同表面(生物和合成表面);(b)在模拟各种血管状况(正常和狭窄动脉)的不同程度狭窄的可控血流条件下;(c)采用不同的灌注血液处理方式。在接下来的章节中,我们将详细描述这种实验方法,它有助于增进对急性冠脉综合征病理生理学的理解(Badimon等人,《动脉硬化》6:312 - 320,1986年;Badimon等人,《实验室与临床医学杂志》110:706 - 718,1987年;Badimon等人,《血液》73:961 - 967,1989年;Mailhac等人,《循环》90:988 - 996,1994年),并且是研究和筛选新型抗血栓和血小板抑制化合物的有用工具(Badimon等人,《血栓与止血》71:511 - 516,1994年;Vilahur等人,《循环》110:1686 - 1693;Vilahur等人,《血栓与止血》92:191 - 200,2004年;Vilahur等人,《心血管研究》61:806 - 816;Vilahur等人,《血栓与止血》98:662 - 669,2007年;Vilahur等人,《血栓与止血》97:650 - 657,2007年;Zafar等人,《血栓与止血杂志》5:1195 - 1200,2007年;Lev等人,《美国心脏病学会杂志》43:966 - 971),以及用于评估与合成/人工表面(Badimon等人,《生物材料应用杂志》5:27 - 48,1990年;Badimon等人,《美国人工脏器学会会刊》33:621 - 625,1987年)和/或血浆成分(胆固醇、血糖水平等)(Badimon等人,《动脉硬化血栓形成》11:395 - 402,1991年;Osende等人,《美国心脏病学会杂志》38:1307 - 1312;2001年)相关的血栓形成倾向。