DIFFERENTIAL SENSITIVITY OF ERYTHROCYTE-RICH AND PLATELET-RICH ARTERIAL THROMBI TO LYSIS WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR - A POSSIBLE EXPLANATION FOR RESISTANCE TO CORONARY THROMBOLYSIS
DIFFERENTIAL SENSITIVITY OF ERYTHROCYTE-RICH AND PLATELET-RICH ARTERIAL THROMBI TO LYSIS WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR - A POSSIBLE EXPLANATION FOR RESISTANCE TO CORONARY THROMBOLYSIS
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DOI：
10.1161/01.cir.79.4.920
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发表时间：
1989-04-01
期刊：
影响因子：
37.8
通讯作者：
COLLEN, D
中科院分区：
文献类型：
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作者：
JANG, IK;GOLD, HK;COLLEN, D
急性心肌梗死是由冠状动脉闭塞引发的，溶栓治疗可以再通，成功率仅为75%。冠状动脉闭塞对溶栓的抵抗可能是由于非血栓机制对管腔的阻塞，也可能是由于血栓对溶解的固有抵抗。冠状动脉血栓是由富含血小板和富含红细胞的物质按不同比例组成。为了评估这些血栓成分对溶栓的相对敏感性，我们在兔股动脉建立了两种血栓模型，一种是在分离的节段注入全血和凝血酶产生的富红细胞血栓，另一种是在股动脉外翻(由内向外)自发形成的富含血小板的血栓。静脉输注重组组织型纤溶酶原激活剂(rt-PA)的速率为30µg/kg/分钟，持续灌流被富含红细胞的凝块堵塞的动脉(6只动物中有6只动物为零，而安慰剂组6只动物中为零，p=0.002)，而输注30或100ug/kg/min的重组组织型纤溶酶原激活剂(rt-PA)对于被富含血小板材料堵塞的外翻节段的再灌注效率显著降低(12只动物中只有4只，p=0.01)。以20微克/公斤/分钟的速度在闭塞附近动脉内输注，7只兔中6只有富含红细胞的凝块，而7只兔中只有1只有闭塞的外翻节段(p=0.03)。在6只兔中，有5只需要100微克/公斤/分钟的剂量才能使富含血小板的闭塞血管再通。我们得出结论，富含血小板的动脉血栓比富含红细胞的血栓对rt-PA溶栓更具抵抗力。这种对溶解的不同敏感性可能解释了在很大比例的急性心肌梗死患者中溶栓治疗失败的原因，这些患者可能主要是富含血小板的闭塞。兔股动脉外翻移植物模型可作为开发富含血小板血栓溶解策略的有用工具。
Acute myocardial infarction is triggered by coronary artery occlusion that may be recanalized by thrombolytic therapy with a success rate of up to 75% only. The resistance of coronary artery occlusion to thrombolysis may either be due to obstruction of the lumen by a nonthrombotic mechanism or by intrinsic resistance of thrombus to dissolution. Coronary arterial thrombi are composed of platelet-rich and erythrocyte-rich material in variable proportions. To evaluate the relative sensitivity of these thrombus components to thrombolysis, we have used two femoral arterial thrombosis models in the rabbit, consisting of erythrocyte-rich clot produced by injecting whole blood and thrombin in an isolated segment and of platelet-rich thrombus spontaneously formed on an everted (inside out) femoral arterial segment. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 30 .mu.g/kg/min consistently reperfused arteries occluded with erythrocyte-rich clot (six of six animals compared with zero of six placebo-treated animals, p = 0.002), whereas infusion of 30 or 100 .mu.g/kg/min was significantly less efficient for reperfusion of everted segments occluded with platelet-rich material (only four of 12 animals, p = 0.01). Intra-arterial infusion proximal to the occlusion, at a rate of 20 .mu.g/kg/min reperfused six of seven rabbits with erythrocyte-rich clots but only one of seven rabbits with occluded everted segments (p = 0.03). A dose of 100 .mu.g/kg/min was necessary to reperfuse platelet-rich occlusions in five of six rabbits. We conclude that platelet-rich arterial thrombus is much more resistant to thrombolysis with rt-PA than erythrocyte-rich clot. This differential sensitivity to lysis may explain the failure of thrombolytic therapy in a significant percentage of patients with acute myocardial infarction who may have a predominantly platelet-rich occlusion. The rabbit femoral arterial eversion graft model may represent a useful tool for developing strategies directed at the dissolution of platelet-rich thrombus.