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.
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.
Fincke
U
U
Center of Research, Grünenthal GmbH, Aachen, Fed. Rep. of Germany.
Schneider
J
J
Friderichs
E
E
Giertz
H
H
Flohé
L
L
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*
D011994:Recombinant Proteins; D005340:Fibrinogen; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator