title: Comparative effects of tissue plasminogen activator, streptokinase, and staphylokinase on cerebral ischemic infarction and pulmonary clot lysis in hamster models.
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.
  
  
  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 approximately 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 alpha(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.
authors.affiliation: Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Nagai
authors.forename: I
authors.initials: I
authors.lastname: Vanlinthout
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D000818:Animals; D017536:Carotid Artery, Common; D002544:Cerebral Infarction / Q000188:drug therapy*; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000032:analysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D008647:Mesocricetus; D008666:Metalloendopeptidases / Q000494:pharmacology* / Q000633:toxicity; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use* / Q000633:toxicity; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use* / Q000633:toxicity; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus