Division of Cardiovascular Medicine, University of California San Francisco, Fresno, CA 93721, USA.
Thromb Res. 2010 Nov;126(5):426-30. doi: 10.1016/j.thromres.2010.07.021. Epub 2010 Sep 1.
Enhanced thrombolysis is a proposed mechanism for reduced mortality in cigarette smokers with STEMI ("smoker's paradox"). The mechanisms remain unclear but studies suggest fibrin architecture (FA) may affect thrombolysis. Our group has previously shown that acute cigarette smoke exposure (CSE) alters FA. This study was done to evaluate the association between FA, thrombolysis and CSE.
Otherwise healthy smokers (n=22) were studied before and after smoking two cigarettes. Non-smokers (n=22) served as controls. Two ex-vivo models were used to evaluate clot lysis of venous blood and these data were compared to FA as determined by SEM. In the first model, clot lysis in a glass tube at 60minutes after addition of t-PA was measured. The second model quantified lysis utilizing thromboelastography. With the latter, after a clot reached maximum strength, t-PA was added and clot lysis at 60min was noted. SEM studies were performed on platelet poor plasma mixed with thrombin and FA was examined at 20K. Clot lysis was similar in both groups except that post-smoking, TEG showed a significantly lower lysis compared to pre- and non-smoking clots. SEM analysis showed significantly thinner fibers and denser clots post-smoking.
Venous clots from smokers failed to show an enhanced lysis when exposed to t-PA. In fact, acute CSE was associated with changes in FA and increased resistance to thrombolysis. These findings in part may explain enhanced thrombogenicity but suggest that mechanisms other than enhanced fibrinolysis are likely to be responsible for "smoker's paradox."
增强的溶栓作用是 STEMI （“吸烟者悖论”）中吸烟患者死亡率降低的一个推测机制。但机制尚不清楚，研究表明纤维蛋白结构（FA）可能会影响溶栓。我们的小组之前已经表明，急性吸烟暴露（CSE）会改变 FA。本研究旨在评估 FA、溶栓和 CSE 之间的关联。
我们研究了 22 名健康吸烟者在吸烟两支香烟前后的情况。22 名不吸烟者作为对照组。使用两种离体模型评估静脉血的血凝块溶解情况，并将这些数据与 SEM 确定的 FA 进行比较。在第一个模型中，在加入 t-PA 后 60 分钟测量玻璃管中的血凝块溶解情况。第二个模型利用血栓弹性描记术量化了溶解情况。在后一种情况下，当血凝块达到最大强度后，加入 t-PA，并记录 60 分钟的血凝块溶解情况。在血小板缺乏的血浆中混合凝血酶进行 SEM 研究，并在 20K 下检查 FA。两组的血凝块溶解情况相似，但在吸烟后，TEG 显示的溶解明显低于吸烟前和不吸烟的血凝块。SEM 分析显示吸烟后纤维明显变薄，血凝块更致密。
暴露于 t-PA 时，来自吸烟者的静脉血栓未能显示出增强的溶解。事实上，急性 CSE 与 FA 的变化以及对溶栓的抵抗力增加有关。这些发现部分解释了增强的血栓形成性，但表明除了增强的纤维蛋白溶解之外，可能还有其他机制导致了“吸烟者悖论”。
