Koster R W, van Stralen R, McNeill A J, Adgey A A, Fox K A, Dymond D, Sponzilli C, Jewitt D, Bucknall C, Kluft C
Academic Medical Centre, Amsterdam, The Netherlands.
Eur Heart J. 1990 Aug;11(8):730-9. doi: 10.1093/oxfordjournals.eurheartj.a059788.
This study was designed to examine the relationships between dose of Wellcome two-chain recombinant tissue type-plasminogen activator (BW rt-PA) and coronary patency and fibrinolytic parameters in acute myocardial infarction (AMI). In an open randomized study, patients with AMI (determined by ECG) and symptoms of less than 4 h duration without contraindications for fibrinolytic therapy were treated with rt-PA in nominal doses of 20 (7.7 MU), 50 (14.8-29.6 MU) or 100 mg (29.6-48.2 MU) administered over 90 min followed by intravenous heparin. Coronary patency was determined by coronary arteriography of the infarct-related artery and haematological parameters (fibrinogen, plasminogen, alpha 2-antiplasmin and fibrin(ogen) degradation products) measured at 90 min. Coronary patency increased in a dose-related manner to 53% (95% C.I. 37-69%) in the 100 mg/90 min group. Logistic regression demonstrated a relationship between dose (in MU kg-1) and coronary patency. Fibrinogen at 90 m was reduced to 74 (61.5-86.4%) of the pooled plasma standard in the nominal 100 mg group. Patients with a higher predose fibrinogen had higher reductions of fibrinogen. Serious bleeding occurred in three (3%) patients, and no intracranial bleeds were reported. BW rt-PA produces dose-related patency of the coronary arteries with moderate, dose-related reduction in fibrinogen.
本研究旨在探讨惠康双链重组组织型纤溶酶原激活剂（BW rt-PA）剂量与急性心肌梗死（AMI）患者冠状动脉通畅率及纤溶参数之间的关系。在一项开放随机研究中，对心电图确诊为AMI且症状持续时间少于4小时、无纤溶治疗禁忌证的患者，给予90分钟内静脉输注名义剂量为20（7.7 MU）、50（14.8 - 29.6 MU）或100 mg（29.6 - 48.2 MU）的rt-PA，随后静脉注射肝素。通过梗死相关动脉的冠状动脉造影确定冠状动脉通畅情况，并在90分钟时测量血液学参数（纤维蛋白原、纤溶酶原、α2-抗纤溶酶和纤维蛋白（原）降解产物）。冠状动脉通畅率在100 mg/90分钟组呈剂量依赖性增加至53%（95%置信区间37 - 69%）。逻辑回归显示剂量（以MU kg-1计）与冠状动脉通畅率之间存在关系。在名义剂量100 mg组中，90分钟时纤维蛋白原降至合并血浆标准的74%（61.5 - 86.4%）。给药前纤维蛋白原水平较高的患者纤维蛋白原降低幅度更大。3例（3%）患者发生严重出血，未报告颅内出血。BW rt-PA可产生剂量依赖性的冠状动脉通畅，同时纤维蛋白原呈适度的剂量依赖性降低。
