van Griensven J M, Koster R W, Burggraaf J, Huisman L G, Kluft C, Kroon R, Schoemaker R C, Cohen A F
Academic Medical Center, Amsterdam, The Netherlands.
Clin Pharmacol Ther. 1998 Jan;63(1):39-47. doi: 10.1016/S0009-9236(98)90119-9.
The removal of recombinant tissue-type plasminogen activator (rt-PA; alteplase) by the liver is so rapid that liver blood flow becomes rate determining for its clearance. In patients with myocardial infarction changes in liver blood flow may result from impaired cardiac performance or drug treatment.
To estimate the effect of variations in liver blood flow on t-PA plasma concentrations during thrombolytic therapy.
Fifteen patients with acute myocardial infarction were investigated in an open single-center study at the coronary care unit of University Hospital Leiden. Patients received thrombolytic treatment with 100 mg rt-PA over 3 hours. Liver blood flow was estimated by indocyanine green clearance and by Doppler echocardiography. Concentrations of t-PA antigen, t-PA activity, indocyanine green, alpha 2-antiplasmin, fibrinogen, and fibrin and fibrinogen degradation products were measured.
Indocyanine green clearance and clearance of both t-PA antigen (r = 0.78; p < 0:01) and t-PA activity (r = 0.54; p < 0.05) were significantly related. Significant associations between t-PA antigen and fibrin and fibrinogen degradation products and between t-PA antigen and alpha 2-antiplasmin were also found.
The liver blood flow of patients with myocardial infarction is inversely correlated with plasma concentrations of t-PA. In patients with severely impaired liver blood flow and heart failure, high t-PA plasma concentrations may occur if standard doses are given. This finding could contribute to optimization of the dosage of t-PA in certain patient groups.
肝脏对重组组织型纤溶酶原激活剂（rt-PA；阿替普酶）的清除速度极快，以至于肝血流量成为其清除的速率决定因素。在心肌梗死患者中，肝血流量的变化可能由心脏功能受损或药物治疗引起。
评估溶栓治疗期间肝血流量变化对t-PA血浆浓度的影响。
在莱顿大学医学中心冠心病监护病房进行的一项开放性单中心研究中，对15例急性心肌梗死患者进行了调查。患者在3小时内接受100mg rt-PA溶栓治疗。通过吲哚菁绿清除率和多普勒超声心动图评估肝血流量。测量t-PA抗原、t-PA活性、吲哚菁绿、α2-抗纤溶酶、纤维蛋白原以及纤维蛋白和纤维蛋白原降解产物的浓度。
吲哚菁绿清除率与t-PA抗原清除率（r = 0.78；p < 0.01）和t-PA活性清除率（r = 0.54；p < 0.05）均显著相关。还发现t-PA抗原与纤维蛋白和纤维蛋白原降解产物之间以及t-PA抗原与α2-抗纤溶酶之间存在显著关联。
心肌梗死患者的肝血流量与t-PA血浆浓度呈负相关。在肝血流量严重受损和心力衰竭的患者中，如果给予标准剂量，可能会出现高t-PA血浆浓度。这一发现有助于优化特定患者群体中t-PA的剂量。
