In vivo dynamic real-time monitoring and quantification of platelet-thrombus formation: use of a local isotope detector.

In vivo dynamic real-time monitoring and quantification of platelet-thrombus formation: use of a local isotope detector.
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血小板血栓形成的体内动态实时监测和定量:使用局部同位素检测器。

DOI:
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发表时间:
2000
期刊:
Arteriosclerosis, Thrombosis and Vascular Biology
影响因子:
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通讯作者:
J. Badimón
J. Badimón
中科院分区:
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文献类型:
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作者:
A. Zaman;J. Osende;J. Chesebro;V. Fuster;A. Padurean;R. Gallo;S. Worthley;G. Helft;O. Rodríguez;J. Fallon;J. Badimón

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目前监测血栓形成和血栓生长的方法是侵入性的,只提供单一时间点的数据。动物模型主要依靠血流变化作为血栓形成的替代指标。我们的目的是通过使用猪颈动脉损伤模型来验证一种独特的潜在的非侵入性系统来检测和量化体内动态血栓的形成。血栓生长的监测是通过使用微型伽马探测器和多普勒血流在受损动脉上沉积自体(111)In标记的血小板活性来进行的。每隔2分钟记录一次计数,持续2小时。通过将标准抗血栓药物与对照组进行比较,该技术得到了验证。在血流量发生显著变化之前,检测到了血小板的重新聚集。血栓形成以曲线下面积(血小板x分钟x 10(6))计算,对照组动物血栓形成最多(11.7+/-1.28),其次是阿司匹林组(6.13+/-0.91,P<0.05)、肝素组(2.45+/-0.34,P<0.05)和水飞蓟素组(0.2+/-0.01,P<0.01与肝素组相比)。以下治疗组动物的血小板沉积率被评估为前30分钟的曲线斜率(每分钟血小板×10(6)):对照组3.53+/-0.34;阿司匹林1.67+/-0。肝素1.55+/-0.3(P<0.01);水飞蓟素0.25+/-0.03(P<0.001)。肝素和阿司匹林治疗之间没有统计学差异。血流量变化被评估为较基线减少:对照组,99+/-0.34%;阿司匹林,39+/-9.1%;肝素,36+/-12。5%;水飞蓟素,17+/-5.4%。阿司匹林治疗组和肝素治疗组之间没有统计学差异。形态计量学分析显示,对照组管腔内血栓闭塞99+/-0.63%,阿司匹林治疗组43+/-14.3%,肝素治疗组30+/-5.6%,水飞蓟素组<10+/-1.8%。用这项技术评估血小板-血栓形成在确定抗血栓疗效方面比血流改变更敏感,而且血栓形成被更早地检测出来。这项研究验证了一种新的定量、灵敏、潜在的非侵入性、便携式、体内动态血栓生长监测方法,该方法似乎适用于人类II期研究。
Current methods for monitoring thrombosis and thrombus growth are invasive and provide only single-time-point data. Animal models rely mainly on flow changes as a surrogate of thrombus formation. Our aim was to validate a unique potentially noninvasive system to detect and quantify dynamic thrombus formation in vivo by using a porcine model of carotid artery injury. Thrombus growth was monitored by deposition of autologous (111)In-labeled platelet activity over the injured artery by use of miniaturized gamma detectors and Doppler blood flow. Counts were recorded at 2-minute intervals for 2 hours. The technique was validated by comparing standard antithrombotic agents against controls. Platelet recruitment was detected before significant change in flow. Thrombus formation, calculated as the area under the curve (platelets x minutes x 10(6)), was greatest for control animals (11.7+/-1.28), followed by animals treated with aspirin (6.13+/-0.91, P<0.05), heparin (2.45+/-0.34, P<0.05), and hirudin (0.2+/-0.01, P<0.01 compared with heparin). The rate of platelet deposition was assessed as the slope of the curve in the first 30 minutes (platelets x 10(6) per minute) for the following treatment groups of animals: control, 3.53+/-0.34; aspirin, 1.67+/-0. 34 (P<0.01); heparin, 1.55+/-0.3 (P<0.01); and hirudin, 0.25+/-0.03 (P<0.001). There was no statistical difference between heparin and aspirin treatments. Change in flow was assessed as reduction from baseline: control, >99+/-0.34%; aspirin, 39+/-9.1%; heparin, 36+/-12. 5%; and hirudin, 17+/-5.4%. There was no statistical difference between the aspirin- and heparin-treated groups. Morphometric analysis revealed >99+/-0.63% occlusion of the luminal area with thrombus for the control group, 43+/-14.3% for the aspirin-treated group, 30+/-5.6% for the heparin-treated group, and <10+/-1.8% for the hirudin-treated group. Assessment of platelet-thrombus formation with this technique was more sensitive than change in flow in determining antithrombotic efficacy, and thrombus formation was detected earlier. This study validates a new quantitative, sensitive, potentially noninvasive, portable, in vivo monitoring of dynamic thrombus growth, which appears applicable to phase II studies in humans.
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