Newby D E, Witherow F N, Wright R A, Bloomfield P, Ludlam C A, Boon N A, Fox K A A, Webb D J
Department of Cardiology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK.
Heart. 2002 Jan;87(1):48-53. doi: 10.1136/heart.87.1.48.
To assess acute tissue plasminogen activator (t-PA) release in vivo in patients with hypercholesterolaemia in the presence and absence of lipid lowering treatment and in matched normocholesterolaemic controls.
Parallel group comparison and double blind randomised crossover.
University hospital.
Eight patients with hypercholesterolaemia (> 7.8 mmol/l) and eight matched normocholesterolaemic controls (< 5.5 mmol/l).
Blood flow and plasma fibrinolytic factors were measured in both forearms during unilateral brachial artery infusions of the endothelium dependent vasodilator substance P (2-8 pmol/min) and the endothelium independent vasodilator sodium nitroprusside (1-4 microg/min).
In patients, measurements were made on three occasions: at baseline and after six weeks of placebo or pravastatin 40 mg daily administered in a double blind randomised crossover design.
Acute release of t-PA.
Compared with patients, in normocholesterolaemic control subjects substance P caused greater dose dependent increases in forearm blood flow (p < 0.05) but similar increases in plasma t-PA antigen and activity concentrations. During pravastatin treatment in patients, total serum cholesterol fell by 22% from a mean (SEM) of 8.1 (0.3) to 6.4 (0.4) mmol/l (p = 0.002) and substance P induced vasodilatation was no longer significantly impaired in comparison with controls. However, despite reproducible responses, pravastatin treatment was not associated with significant changes in basal or substance P induced t-PA release.
Hypercholesterolaemia and lipid lowering treatment cause no demonstrable effects on acute substance P induced t-PA release in vivo. This suggests that the preventative benefits of lipid lowering treatment are unlikely to be mediated by improvements in endogenous fibrinolysis.
评估在接受或未接受降脂治疗的高胆固醇血症患者以及匹配的正常胆固醇血症对照者体内，急性组织型纤溶酶原激活剂（t-PA）的释放情况。
平行组比较和双盲随机交叉试验。
大学医院。
8例高胆固醇血症患者（>7.8 mmol/l）和8例匹配的正常胆固醇血症对照者（<5.5 mmol/l）。
在单侧肱动脉输注内皮依赖性血管扩张剂P物质（2 - 8 pmol/分钟）和内皮非依赖性血管扩张剂硝普钠（1 - 4 μg/分钟）期间，测量双侧前臂的血流和血浆纤溶因子。
对患者进行三次测量：基线时以及在双盲随机交叉设计中给予安慰剂或每日40 mg普伐他汀治疗六周后。
t-PA的急性释放。
与患者相比，正常胆固醇血症对照者中，P物质引起前臂血流更大的剂量依赖性增加（p < 0.05），但血浆t-PA抗原和活性浓度的增加相似。在患者接受普伐他汀治疗期间，总血清胆固醇从平均（SEM）8.1（0.3）mmol/l降至6.4（0.4）mmol/l，下降了22%（p = 0.002），与对照相比，P物质诱导的血管扩张不再受到明显损害。然而，尽管反应可重复，但普伐他汀治疗与基础或P物质诱导的t-PA释放的显著变化无关。
高胆固醇血症和降脂治疗对体内急性P物质诱导的t-PA释放没有明显影响。这表明降脂治疗的预防益处不太可能通过内源性纤溶的改善来介导。
