title: Enhanced myocardial salvage by combined treatment with recombinant single-chain urokinase-type plasminogen activator and recombinant human superoxide dismutase in a canine coronary thrombosis model.
abstract: Myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX) in open chest dogs. The myocardial salvage by the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA) alone and in combination with the oxygen radical scavenger human superoxide dismutase of recombinant origin (r-HSOD) was investigated. The three experimental groups were: group I (n = 4) did not receive any treatment after LCX thrombosis; in group II (n = 9) at 100 min after LCX thrombosis r-scu-PA (20 micrograms.kg1.min-1 i.v. for 30 min) was infused; dogs in group III (n = 8) received concomitant treatment with r-scu-PA and r-HSOD (10 mg.kg1 i.v. for 60 min). Percent of left ventricle at risk did not differ between the groups. Infarct size as percent of the risk zone was 45.3 +/- 8.0 in group I, 25.3 +/- 3.7 in group II (a less than or equal to 0.05 vs group I) and 14.9 +/- 3.2 in group III (a less than 0.05 vs group II). Incidence of reperfusion arrhythmias and increase in plasma creatine kinase were significantly diminished by r-HSOD when compared to dogs receiving r-scu-PA only. There were no significant differences in hemodynamic parameters between the groups. No changes in plasma fibrinogen were observed in r-scu-PA treated dogs. In conclusion, the combined treatment with r-scu-PA and r-HSOD yielded a significantly higher myocardial salvage versus thrombolytic treatment alone in a canine LCX thrombosis model.
authors: Center of Research, Grünenthal GmbH, Aachen, Fed. Rep. of Germany.
authors: U
authors: U
authors: Fincke
authors: J
authors: J
authors: Schneider
authors: E
authors: E
authors: Friderichs
authors: H
authors: H
authors: Giertz
authors: L
authors: L
authors: Flohé
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D005340:Fibrinogen; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator