Witt W, Maass B, Baldus B, Hildebrand M, Donner P, Schleuning W D
Department of Cardiovascular Pharmacology, Research Laboratories of Schering AG, Berlin, Germany.
Circulation. 1994 Jul;90(1):421-6. doi: 10.1161/01.cir.90.1.421.
DSPA (Desmodus salivary plasminogen activator) is a new thrombolytic agent corresponding to a natural plasminogen activator discovered in the saliva of the vampire bat Desmodus rotundus. Compared with tissue plasminogen activator (TPA), DSPA, produced in a recombinant cell line, is more fibrin cofactor dependent than TPA.
The thrombolytic properties of DSPA and TPA were compared in a canine model of copper coil-induced coronary thrombosis. All dogs received heparin 200 IU/kg IV and SC. Whereas controls did not reperfuse within 180 minutes (none of six), intravenous bolus administration of DSPA at 25, 50, and 100 micrograms/kg resulted in a 100% incidence (6 of 6) of recanalization within 37, 23, and 18 minutes, respectively. TPA at 63 and 125 micrograms/kg reopened the coronaries in 33% (two of six) and 50% (three of six) of cases within 40 minutes. Eighty-three percent (5 of 6) of the arteries were still patent 3 hours after 50 and 100 micrograms/kg DSPA, whereas only 20% (one of five) of all coronaries originally recanalized with both doses of TPA were still open at 3 hours. Plasma levels of alpha 2-antiplasmin decreased significantly only with 125 micrograms/kg TPA. The clearance of DSPA (2.3 to 3.5 mL.min-1.kg-1) was lower compared with TPA (11.4 to 20 mL.min-1.kg-1) due to a prolonged terminal half-life.
In a canine coronary thrombosis model, DSPA exhibited higher potency and recanalized coronary arteries faster and with a lower incidence of reocclusion than TPA. Its properties may translate into a higher efficacy in patients compared with available thrombolytic agents. The long half-life of DSPA may allow for single bolus administration in the treatment of acute myocardial infarction.
吸血蝙蝠唾液纤溶酶原激活剂（DSPA）是一种新型溶栓剂，对应于在圆叶吸血蝠唾液中发现的一种天然纤溶酶原激活剂。与组织纤溶酶原激活剂（TPA）相比，在重组细胞系中产生的DSPA比TPA更依赖纤维蛋白辅因子。
在铜线圈诱导的犬冠状动脉血栓形成模型中比较了DSPA和TPA的溶栓特性。所有犬静脉内和皮下注射200 IU/kg肝素。对照组在180分钟内未再灌注（6只中无1只），静脉推注25、50和100微克/千克的DSPA分别在37、23和18分钟内导致再通发生率为100%（6只中的6只）。63和125微克/千克的TPA在40分钟内分别使33%（6只中的2只）和50%（6只中的3只）的冠状动脉再通。50和100微克/千克DSPA给药3小时后，83%（6只中的5只）的动脉仍保持通畅，而最初用两种剂量TPA再通的所有冠状动脉在3小时时只有20%（5只中的1只）仍开放。仅125微克/千克TPA使血浆α2-抗纤溶酶水平显著降低。由于终末半衰期延长，DSPA的清除率（2.3至3.5 mL·min-1·kg-1）低于TPA（11.4至20 mL·min-1·kg-1）。
在犬冠状动脉血栓形成模型中，DSPA比TPA表现出更高的效力，冠状动脉再通更快且再闭塞发生率更低。与现有溶栓剂相比，其特性可能在患者中转化为更高的疗效。DSPA的长半衰期可能允许在急性心肌梗死治疗中单次推注给药。
