Rukshin Vladimir, Shah Prediman K, Cercek Bojan, Finkelstein Ariel, Tsang Vivian, Kaul Sanjay
Vascular Physiology and Thrombosis Research Laboratory of the Atherosclerosis Research Center, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, Calif, USA.
Circulation. 2002 Apr 23;105(16):1970-5. doi: 10.1161/01.cir.0000014612.88433.62.
Antithrombotic effects of glycoprotein IIb/IIIa inhibitors and magnesium are known, but their comparative effects on stent thrombosis are not known. Our objective was to compare the antithrombotic effects of the glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide with magnesium in an ex vivo canine arteriovenous shunt model of stent thrombosis.
Control nitinol stents were expanded to 2 mm in diameter in a tubular perfusion chamber interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s(-1) for 20 minutes (n=398 perfusion runs in 24 experiments in 8 dogs). The animals were treated intravenously with MgSO4 (2 g bolus x 20 minutes followed by 2 g/h infusion), eptifibatide (double bolus of 180 microg/kg 10 minutes apart followed by 2 microg/kg per minute), or tirofiban (0.3 microg/kg per minute), with or without heparin (50 U/kg). Effects of the test agents on thrombus weight, platelet aggregation (PA), platelet CD62 expression, bleeding time (BT), heart rate, and mean arterial blood pressure were assessed. Treatment with Mg+heparin reduced stent thrombus weight by 78+/-10% compared with baseline (19+/-4 mg, P<0.001). The antithrombotic effect of Mg+heparin was equivalent to that observed with tirofiban+heparin (78+/-13%) and eptifibatide+heparin (84+/-11%). Magnesium had no significant effect on PA and BT. Tirofiban and eptifibatide inhibited PA by >90% and prolonged BT up to 20 minutes. None of the test agents had effects on CD62 expression or activated clotting time. There were no significant bleeding or hemodynamic complications.
Magnesium produced a significant reduction in acute stent thrombus formation that was equivalent in magnitude to that produced by clinically relevant doses of tirofiban and eptifibatide. Its potential use in percutaneous coronary intervention requires further study.
糖蛋白IIb/IIIa抑制剂和镁的抗血栓作用已为人所知，但它们对支架内血栓形成的比较作用尚不清楚。我们的目的是在支架内血栓形成的体外犬动静脉分流模型中，比较糖蛋白IIb/IIIa抑制剂替罗非班和依替巴肽与镁的抗血栓作用。
将对照镍钛合金支架在置于分流管中的管状灌注室中扩张至直径2 mm，并以2100 s(-1)的剪切速率暴露于流动的动脉血中20分钟（8只犬的24项实验中进行了398次灌注运行）。动物静脉注射硫酸镁（2 g推注×20分钟，随后以2 g/h输注）、依替巴肽（两次推注，每次180 μg/kg，间隔10分钟，随后以2 μg/kg每分钟输注）或替罗非班（0.3 μg/kg每分钟），同时或不同时使用肝素（50 U/kg）。评估受试药物对血栓重量、血小板聚集（PA）、血小板CD62表达、出血时间（BT）、心率和平均动脉血压的影响。与基线相比，镁+肝素治疗使支架血栓重量减少了78±10%（19±4 mg，P<0.001）。镁+肝素的抗血栓作用与替罗非班+肝素（78±13%）和依替巴肽+肝素（84±11%）观察到的作用相当。镁对PA和BT无显著影响。替罗非班和依替巴肽抑制PA超过90%，并使BT延长至20分钟。受试药物均对CD62表达或活化凝血时间无影响。无明显出血或血流动力学并发症。
镁可显著减少急性支架内血栓形成，其程度与临床相关剂量的替罗非班和依替巴肽相当。其在经皮冠状动脉介入治疗中的潜在用途需要进一步研究。
