Killewich L A, Gardner A W, Macko R F, Hanna D J, Goldberg A P, Cox D K, Flinn W R
Department of Surgery, University of Maryland Medical School, Baltimore, USA.
J Vasc Surg. 1998 Apr;27(4):645-50. doi: 10.1016/s0741-5214(98)70229-0.
Acute complications of atherosclerosis such as stroke and myocardial infarction are caused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to determine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1).
The study group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walking distance > or = 200 meters) and 51 patients with severe claudication (SC, walking distance <200 meters). Eleven age- and sex-matched patients without PAD served as controls. All patients had measurements of serum tPA antigen using an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean +/- SEM levels of the enzyme levels in patients with progressively more severe PAD were compared with normal controls.
Serum PAI-1 activity levels were significantly elevated in both PAD groups compared with normal controls (p < 0.02). There were no significant differences in the PAI-1 activity levels in groups with worsening degrees of PAD. There was a significant decrease in tPA activity levels in patients with SC (p = 0.01) relative to those with MC and the normal subjects. There was also a significant increase in tPA antigen level in the patients with SC compared with those with MC and the control subjects, as well as a significant inverse correlation between tPA antigen levels and pain-free walking time in patients with claudication (p = 0.001).
All patients with PAD in this study had significant reductions in endogenous fibrinolytic activity. Patients with SC had more impaired fibrinolytic activity than those with MC and the control subjects, suggesting that the progression to more severe levels of PAD may be associated with worsening endogenous fibrinolysis.
动脉粥样硬化的急性并发症如中风和心肌梗死是由血栓形成引起的，并且可能与纤维蛋白溶解活性受损有关。本研究旨在通过测量组织型纤溶酶原激活物（tPA，纤维蛋白溶解的激活物）及其抑制剂纤溶酶原激活物抑制剂-1（PAI-1）来确定外周动脉疾病（PAD）及其进展是否也与纤维蛋白溶解受损有关。
研究组由80名平均年龄为69岁的男性组成。其中包括18名轻度间歇性跛行患者（MC，无痛行走距离≥200米）和51名重度跛行患者（SC，行走距离<200米）。11名年龄和性别匹配的无PAD患者作为对照。所有患者均采用酶联免疫吸附测定法测量血清tPA抗原。采用酰胺水解法测定血清tPA和PAI-1活性水平。将PAD逐渐加重的患者的酶水平均值±标准误与正常对照组进行比较。
与正常对照组相比，两个PAD组的血清PAI-1活性水平均显著升高（p<0.02）。PAD程度加重的组间PAI-1活性水平无显著差异。与MC患者和正常受试者相比，SC患者的tPA活性水平显著降低（p = 0.01）。与MC患者和对照组相比，SC患者的tPA抗原水平也显著升高，并且跛行患者的tPA抗原水平与无痛行走时间之间存在显著的负相关（p = 0.001）。
本研究中所有PAD患者的内源性纤维蛋白溶解活性均显著降低。SC患者的纤维蛋白溶解活性比MC患者和对照组更受损，表明进展到更严重程度的PAD可能与内源性纤维蛋白溶解恶化有关。
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