Affiliation:
1. From the Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium (N.N., I.V., D.C.), and the Department of Physiology, Hamamatsu University School of Medicine, Japan (N.N.).
Abstract
Background
—The effects of alteplase (rtPA), streptokinase, and staphylokinase (rSak) on focal cerebral ischemia (FCI) and on pulmonary clot lysis (PCL) were studied in hamsters.
Methods and Results
—FCI was produced by ligation of the left middle cerebral artery (MCA) and common carotid artery (CCA) and a 10-minute occlusion of the right CCA. FCI was measured after 24 hours by 2,3,5-triphenyltetrazolium chloride staining.
125
I-fibrin–labeled plasma clots were injected via the jugular vein, and clot lysis was determined from residual radioactivity at 90 minutes. Study drugs were given intravenously over 60 minutes. FCI increased from 1.2 (0.27 to 2.3) mm
3
(median and 17th to 83rd percentile range, n=24) in controls to 19 to 27 mm
3
with thrombolytic agent, with maximal rates at 0.13±0.05 mg/kg rtPA, 0.23±0.09 mg/kg streptokinase, and 0.037±0.025 mg/kg rSak. PCL increased from 18±2% (mean±SEM, n=27) in controls to ≈85% with thrombolytics, with maximal rates at 0.12±0.03 mg/kg rtPA, 0.17±0.05 mg/kg streptokinase, and 0.018±0.002 mg/kg rSak. All agents caused maximal FCI and PCL rates at similar doses without α
2
-antiplasmin and fibrinogen depletion. Injection of 6 mg/kg human plasminogen combined with streptokinase caused a “systemic fibrinolytic state” with fibrinogen depletion. Maximal rates of FCI were obtained with 0.097±0.077 mg/kg streptokinase (
P
=0.26 versus streptokinase alone) and of PCL with 0.010±0.002 mg/kg (
P
=0.006 versus streptokinase alone).
Conclusions
—Thrombolytic agents cause similar dose-related extension of FCI after MCA ligation and PCL, irrespective of the agent or systemic plasmin generation.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
40 articles.
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