Research of prevention and mechanisms for coronary reocclusion after coronary thrombolytic therapy

冠脉再通后再闭塞往往限制了急性心肌梗死患者溶栓治疗的疗效。急性心肌梗死患者纤溶系统受损。纤溶活性的主要调节元件是纤溶酶原激活物抑制物(PAI)。检测重组组织型纤溶酶原激活物(t-PA)治疗前后PAI活性和t-PA抗原的动态变化。血浆PAI活性水平在入院时即升高，并在24小时内进一步升高。血浆PAI活性水平在开始应用rt-PA后4小时(27.0±2.9)和16小时(25.6±2.5)出现两个峰值(IU/ml)。PAI活性的早期升高可能降低rt激活蛋白C(APC)的再灌注效率，APC是一种重要的止血调节酶。凝血酶-血栓调节蛋白复合体激活内皮细胞后，APC I…更多的灭活因子VIIIa和Va，并导致抑制凝血酶的形成。APC还被证明通过抑制内皮细胞培养和凝块溶解试验中PAI的活性来增强凝块溶解。鉴于人APC具有抗凝和纤溶作用，在犬冠状动脉血栓形成模型上研究了APC对rt-PA溶栓的影响。实验犬随机分为3组：(1)对照组，(2)APC组：APC(0.6 mg/kg)，速度0.83毫升/分钟；(3)肝素组：肝素(200U/kg)，速度0.83毫升/分钟。在终止rt-PA后120分钟的观察中，对照组和肝素组的所有犬都发生了再闭塞，而APC组的10只犬中只有3只发生了再闭塞。APC组从再通到再闭塞的时间较对照组和肝素组延长。仅肝素组治疗后出血时间延长。结论：在犬冠状动脉血栓形成模型中，APC可预防rt-PA再通后的冠状动脉再闭塞。较少

Reocclusion of recanalized coronary arteries often limits the efficacy of coronary thrombolytic therapy in patients with acute myocardial infarction. The fibrinolytic system is impaired in patients with acute myocardial infarction. The primary regulatory element of fibrinolytic activity is plasminogen activator inhibitor (PAI). We measured the serial changes of PAI activity and tissue plasminogen activator (t-PA) antigen after recombinant t-PA (rt-PA) therapy. Plasma PAI activity levels were increased on admission and further increased within 24 hours in patients treated with rt-PA.There were two peaks in plasma PAI activity levels (IU/ml) at 4 hours (27.0<plus-minus>2.9) and at 16 hours (25.6<plus-minus>2.5) after the initiation of rt-PA infusion. The early increase of PAI activity may diminish the efficiency of reperfusion of rtActivated protein C (APC) is an important regulatory enzyme in hemostasis. After activation by thrombin-thrombomodulin complex on the endothelial cells, APC i … More nactivated factors VIIIa and Va and leads to inhibition of thrombin formation. APC also has been shown to enhance clot lysis by inhibiting the activity of PAI in endothelial cell cultures and in clot lysis assays. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the effect of APC on thrombolysis with rt-PA was studied in a canine model of coronary artery thrombosis. The dogs were randomly assigned to receive one of the following intravenous adjunctive hterapies : (1) control group ; (2) APC group : APC (0.6mg/kg) at a rate of 0.83mL/min ; (3) heparin group : heparin (200U/kg) at a rate of 0.83mL/min. In a 120-min observation after the termination of rt-PA,reocclusion developed in all the dogs in the control and heparin groups but in only 3 of the 10 dogs in the APC group. Time from recanalization to reocclusion was prolonged in the APC group as compared with the control and heparin groups. Bleeding time was prolonged in only the heparin group after the treatment. It is concluded that APC prevents coronary artery reocclusion after recanalization with rt-PA in a canine model of coronary artery thrombosis. Less