Mestre M, Uzan A, Sedivy P, Cavero I
Rhone-Poulenc Rorer, Centre de Recherches de Vitry-Alfortville, Vitry-Sur-Seine, France.
Thromb Res. 1992 May 1;66(2-3):191-206. doi: 10.1016/0049-3848(92)90189-h.
An occlusive coronary thrombus was obtained in barbiturate anesthetized dogs within 60 min following the angiographic placement of a copper coil into the left descending coronary artery. This thrombus persisted for the 60 min experimental period, within which the effects of i.v. t-PA (10 micrograms/kg/min for 30 min) alone or combined with i.v. heparin (0.63 mg/kg twice) or enoxaparin (1.5 mg/kg twice) were evaluated. t-PA alone achieved recanalization for 20 min in only 2 out of the 5 dogs studied. Combination of t-PA with either heparin or enoxaparin produced this effect in all the 5 dogs studied. In dogs treated with t-PA associated to either heparin or enoxaparin, the thrombus weight was smaller (decreases of 34% and 44% respectively) than in animals given t-PA alone. The plasma amidolytic activity, expressed as t-PA activity, was greater 15 min after the beginning of t-PA infusion, in dogs pretreated with either heparin or enoxaparin than in animals given t-PA alone. Conversely, during t-PA infusion, the apparent t-PA inhibitor and antiplasmin activities were no longer measurable in the plasma, but reappeared 10 min after the end of t-PA infusion. Plasma coagulation time was not modified by t-PA, but was slightly prolonged (2-fold) by enoxaparin and markedly (7-fold) by heparin on initiation of t-PA infusion. Plasma anti-IIa activity was 3-fold higher in dogs pretreated with heparin as opposed to enoxaparin. On the contrary, both compounds increased similarly plasma anti-Xa activity. In conclusion, these results indicate that enoxaparin, like heparin, enhances the thrombolytic effects of t-PA. This favourable effect occurs independently of a plasma hypocoagulable state, which was clearly produced by heparin but not enoxaparin. Its mechanism may be the significant elevation of plasma t-PA activity produced by both heparin and enoxaparin during t-PA infusion.
在对巴比妥麻醉的犬经血管造影将铜圈置于左冠状动脉降支内60分钟内，获得了闭塞性冠状动脉血栓。该血栓在60分钟的实验期内持续存在，在此期间评估了静脉注射t-PA（10微克/千克/分钟，持续30分钟）单独使用或与静脉注射肝素（0.63毫克/千克，两次）或依诺肝素（1.5毫克/千克，两次）联合使用的效果。单独使用t-PA时，在研究的5只犬中只有2只实现了20分钟的再通。t-PA与肝素或依诺肝素联合使用在所有5只研究犬中均产生了这种效果。在接受t-PA与肝素或依诺肝素联合治疗的犬中，血栓重量比单独给予t-PA的动物更小（分别减少34%和44%）。以t-PA活性表示的血浆酰胺水解活性，在开始输注t-PA 15分钟后，预先用肝素或依诺肝素治疗的犬比单独给予t-PA的动物更高。相反，在输注t-PA期间，血浆中表观t-PA抑制剂和抗纤溶酶活性不再可测，但在t-PA输注结束10分钟后重新出现。血浆凝血时间未被t-PA改变，但在开始输注t-PA时，依诺肝素使其略有延长（2倍），肝素使其显著延长（7倍）。与依诺肝素相比，预先用肝素治疗的犬血浆抗IIa活性高3倍。相反，两种化合物使血浆抗Xa活性同样增加。总之，这些结果表明，依诺肝素与肝素一样，增强了t-PA的溶栓作用。这种有利作用独立于血浆低凝状态而发生，肝素明显产生了这种状态，而依诺肝素则未产生。其机制可能是在输注t-PA期间肝素和依诺肝素均使血浆t-PA活性显著升高。
