Bizjak Nina, Bajd Franci, Vidmar Jernej, Blinc Aleš, Marder Victor J, Novokhatny Valery, Serša Igor
aJožef Stefan Institute bInstitute of Physiology, Medical Faculty of Ljubljana cDepartment of Vascular Diseases, University of Ljubljana Medical Center, Ljubljana, Slovenia dDivision of Hematology/Medical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California eGrifols, Inc., Research Triangle Park, North Carolina, USA fEN-FIST Centre of Excellence, Ljubljana, Slovenia.
Blood Coagul Fibrinolysis. 2013 Oct;24(7):711-4. doi: 10.1097/MBC.0b013e328361bd48.
Plasmin, a directly acting thrombolytic agent, demonstrated a very favorable safety profile upon intra-arterial delivery to the clot site; however, its thrombolytic efficacy remains to be further assessed. In this study, differences in thrombolysis between clots exposed to equimolar concentrations of plasmin and recombinant tissue-type plasminogen activator (rt-PA) after partial vessel recanalization were tested in a model system. Model blood clots were prepared in glass chambers enabling direct observation by dynamic optical microscopy. The incubation of clots with plasmin (2.4 mg/ml) or rt-PA (2.63 mg/ml), allowing for the initial biochemical clot degradation, was followed by 'flushing' the clots with tangentially directed plasma flow devoid of a thrombolytic agent, mimicking blood flow after partial vessel recanalization. The acquired images were analyzed for nondissolved blood clot area as a function of time. With both thrombolytic agents, the relative clot area decreased rapidly in the first 30 s after initiation of perfusion due to 'flushing' the degraded clot fragments (after plasmin by 0.26 ± 0.22 and after rt-PA by 0.34 ± 0.21, P = 0.60). In the following minutes, the clot size showed a linear time dependence: after incubation with plasmin the clot size did not change substantially any more, whereas after incubation with rt-PA the clot size continually decreased. The slopes of the regression lines differed significantly (r(pl) = -8.9 10 vs. r(rtPA) = -44.1 10/min, P < 0.01). In conclusion, the thrombolytic action of plasmin was terminated rapidly by contact with flowing blood plasma, whereas the thrombolytic action of rt-PA was prolonged.
纤溶酶是一种直接作用的溶栓剂，在将其动脉内输送至血栓部位时显示出非常良好的安全性；然而，其溶栓效果仍有待进一步评估。在本研究中，在一个模型系统中测试了部分血管再通后，暴露于等摩尔浓度纤溶酶和重组组织型纤溶酶原激活剂（rt-PA）的血栓之间的溶栓差异。在玻璃腔室中制备模型血凝块，以便通过动态光学显微镜直接观察。用纤溶酶（2.4mg/ml）或rt-PA（2.63mg/ml）孵育血凝块，使血凝块开始生化降解，随后用无溶栓剂的切向血浆流“冲洗”血凝块，模拟部分血管再通后的血流。分析获取的图像，以确定未溶解血凝块面积随时间的变化。使用两种溶栓剂时，由于“冲洗”降解的血凝块碎片，灌注开始后的最初30秒内相对血凝块面积迅速减小（纤溶酶作用后为0.26±0.22，rt-PA作用后为0.34±0.21，P = 0.60）。在接下来的几分钟内，血凝块大小呈线性时间依赖性：用纤溶酶孵育后血凝块大小基本不再变化，而用rt-PA孵育后血凝块大小持续减小。回归线的斜率差异显著（r(pl)= -8.9×10⁻⁴ vs. r(rtPA)= -44.1×10⁻⁴/min，P < 0.01）。总之，纤溶酶的溶栓作用通过与流动血浆接触而迅速终止，而rt-PA的溶栓作用则持续延长。
