Berridge D C, Frier M, Westby J C, Hopkinson B R, Makin G S
Department of Vascular Surgery, University Hospital, Nottingham, UK.
Br J Surg. 1991 Jan;78(1):101-4. doi: 10.1002/bjs.1800780131.
Patients with rest pain or acute peripheral arterial thrombosis are known to have impaired endogenous fibrinolysis, which is associated with an increased risk of early vascular graft thrombosis. This risk is exacerbated by the fibrinolytic shutdown which is known to occur after major surgery. Stanozolol, which has been demonstrated to enhance endogenous fibrinolysis, was therefore used in an attempt to prevent this perioperative fibrinolytic shutdown and so enhance graft patency. Twenty-seven patients were randomized to receive either 50 mg stanozolol or placebo intramuscularly 24 h before operation, followed by a 6 week course of either 5 mg stanozolol or placebo orally, twice daily. On the second day after operation, 10-11 MBq of autologous 111indium-labelled platelets were injected, with scanning over the graft on the 3 following days. Despite using a large depot of stanozolol, significant effects, such as raised plasminogen (P less than 0.001), reduced fibrinogen (P less than 0.001) and reduced euglobulin lysis time (P less than 0.001), were not seen until the seventh day after operation, with maximum benefit at 6 weeks. This was reflected in the 111indium-labelled platelet deposition studies. The placebo group had a progressive increase in platelet deposition on all 3 days. In contrast, those receiving stanozolol showed a lower, static picture of deposition. However, these changes did not attain statistical significance. Three patients experienced early graft thrombosis, two in the placebo group and one in the stanozolol group. Only an incomplete inhibition of the perioperative fibrinolytic shutdown was achieved. Much longer preoperative courses are thus required to allow the maximum effect to be present at the most crucial time. At present, perioperative fibrinolytic enhancement does not appear to be a practical proposition, and we must await the development of new safer and more potent agents.
已知患有静息痛或急性外周动脉血栓形成的患者存在内源性纤维蛋白溶解功能受损的情况，这与早期血管移植血栓形成风险增加有关。大手术后已知会发生的纤维蛋白溶解功能关闭会加剧这种风险。已证明司坦唑醇可增强内源性纤维蛋白溶解，因此被用于尝试预防这种围手术期纤维蛋白溶解功能关闭，从而提高移植物通畅率。27名患者被随机分组，在手术前24小时肌肉注射50毫克司坦唑醇或安慰剂，随后口服5毫克司坦唑醇或安慰剂，疗程为6周，每日两次。手术后第二天，注射10 - 11兆贝克勒尔的自体铟 - 111标记血小板，并在接下来3天对移植物进行扫描。尽管使用了大量的司坦唑醇，但直到手术后第七天才观察到显著效果，如纤溶酶原升高（P小于0.001）、纤维蛋白原降低（P小于0.001）和优球蛋白溶解时间缩短（P小于0.001），6周时效果最佳。这在铟 - 111标记血小板沉积研究中得到了体现。安慰剂组在所有3天内血小板沉积都逐渐增加。相比之下，接受司坦唑醇的患者显示出较低的、稳定的沉积情况。然而，这些变化未达到统计学显著性。3名患者发生了早期移植物血栓形成，安慰剂组2例，司坦唑醇组1例。仅实现了对围手术期纤维蛋白溶解功能关闭的不完全抑制。因此需要更长的术前疗程，以便在最关键的时间出现最大效果。目前，围手术期增强纤维蛋白溶解似乎不是一个切实可行的方案，我们必须等待新的更安全、更有效的药物的研发。
