Bacher P, Welzel D, Iqbal O, Hoppensteadt D, Callas D, Walenga J M, Fareed J
Department of Pathology, Loyola University Medical Center, Maywood, Illinois.
Thromb Res. 1992 May 1;66(2-3):151-8. doi: 10.1016/0049-3848(92)90185-d.
Since the beginning of the clinical use of low molecular weight (LMW) heparins their thrombolytic or profibrinolytic potency has been a matter of controversial discussions. Regarding this problem, the aim of our study was to test a LMW-heparin (Sandoparin) in an in vivo model comparing its lytic activity to unfractionated heparin and urokinase at different doses. For this purpose a newly developed short-term rabbit jugular vein clot lysis model was developed. Urokinase infused at doses of 3300, 6600 and 10,000 U/kg to control animals for one hour showed a clear dose-dependent clot lysis. Test animals were injected with a bolus of 0.5 mg/kg of LMW-heparin followed by a constant infusion of either 0.5, 1.0 or 2.0 mg/kg for one hour. A similar dose-dependent effect was observed for LMW-heparin as for urokinase. Unfractionated heparin did not exhibit a dose-dependent lytic activity in this model. No lysis was found in rabbits treated with saline. These findings suggest that the LMW-heparin tested exhibits a dose-dependent in vivo lytic activity which can be compared to clinically effective doses of urokinase, and that this activity is not present with unfractionated heparin.
自低分子量(LMW)肝素开始临床应用以来,其溶栓或促纤溶效力一直是备受争议的讨论话题。关于这个问题,我们研究的目的是在体内模型中测试一种低分子量肝素(山度肝素),并将其在不同剂量下的溶解活性与普通肝素和尿激酶进行比较。为此,我们开发了一种新的短期兔颈静脉血栓溶解模型。向对照动物输注剂量为3300、6600和10,000 U/kg的尿激酶持续一小时,显示出明显的剂量依赖性血栓溶解。给试验动物静脉推注0.5 mg/kg的低分子量肝素,随后以0.5、1.0或2.0 mg/kg的剂量持续输注一小时。观察到低分子量肝素与尿激酶具有相似的剂量依赖性效应。在该模型中,普通肝素未表现出剂量依赖性溶解活性。用生理盐水处理的兔子未出现血栓溶解。这些发现表明,所测试的低分子量肝素在体内具有剂量依赖性溶解活性,可与临床有效剂量的尿激酶相媲美,而普通肝素则没有这种活性。