Additional myocardial salvage by coadministration of the epoprostenol analog taprostene to recombinant single-chain urokinase-type plasminogen activator in a canine coronary thrombosis model.
In open chest dogs myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX). Reperfusion of the LCX was achieved by infusion of the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA). The myocardial salvage by r-scu-PA alone and in combination with the epoprostenol (prostacyclin) analog taprostene (CG 4203) was compared. There were four experimental groups: group 1 (n = 4) did not receive any treatment after LCX thrombosis; in group 2 (n = 9) at 100 min after LCX thrombosis r-scu-PA (20 micrograms.kg-1.min-1 i.v. for 30 min) was infused; in groups 3 and 4 treatment with taprostene started concomitantly with r-scu-PA infusion. The taprostene infusions lasted for 120 min and the doses were 0.1 microgram.kg-1.min-1 in group 3 (n = 6) and 0.215 microgram.kg-1.min-1 in group 4 (n = 6). Time to r-scu-PA-induced recanalisation ranged from 18-22 min with no significant difference between groups 2-4. Percent of left ventricle at risk did not differ between the groups. Infarct size as percent of the risk zone was 48.3 +/- 7.7 in group 1, 25.3 +/- 3.7 in group 2, 21.3 +/- 6.5 in group 3 and 17.1 +/- 3.5 in group 4 (p less than 0.05 groups 2-4 vs group 1). Incidence of ectopic beats increased after r-scu-PA-induced reperfusion in groups 2-4, but was significantly reduced by taprostene.(ABSTRACT TRUNCATED AT 250 WORDS)
Groves
R
R
Center of Research, Grünenthal GmbH, Aachen, Fed. Rep. of Germany.
Schneider
J
J
Friderichs
E
E
Giertz
H
H
Flohé
L
L
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D003327:Coronary Disease / Q000150:complications*; D003328:Coronary Thrombosis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology* / Q000031:analogs & derivatives; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology*
D011994:Recombinant Proteins; C039188:taprostene; D011464:Epoprostenol; D003402:Creatine Kinase; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator