Effects of heparin, aspirin and a synthetic platelet glycoprotein IIb-IIIa receptor antagonist (Ro 43-5054) on coronary artery reperfusion and reocclusion after thrombolysis with tissue-type plasminogen activator in the dog.
Adjuncts to thrombolytic agents have improved coronary patency and prevented early reocclusion after thrombolysis in acute myocardial infarction. The aim of this study was to compare in a canine thrombolysis model the effects of Ro 43-5054 = N-(N-[N-(p-amidinobenzoyl)-beta-alanyl]-L-alpha-aspartyl)-3- phenyl-L-alanine-trifluor-acetate, a new glycoprotein IIb-IIIa receptor antagonist with aspirin or heparin. Six groups of 10 dogs each were studied. A platelet-rich coronary thrombus was induced in open-chest dogs by electrical stimulation. In addition to recombinant tissue-type plasminogen activator (30 micrograms/kg.min during 60 min), the dogs received 1) saline, 2) heparin 200 U/kg + 50 U/kg.hr i.v., 3) aspirin 10 mg/kg i.v., 4) heparin+aspirin, 5) Ro 43-5054 (3 micrograms/kg.min) and 6) heparin+Ro 43-5054. The overall reperfusion rate was 70% (range, 60-90%) and comparable in all the six groups. During the 120-min observation period, episodes of reocclusion were observed in the absence of antiplatelet therapy (group 1 and 2) irrespective of heparin treatment. Aspirin prevented coronary reocclusion in half of the reperfused dogs (group 3 and 4). However, after reinforcement of the thrombogenic stimulus, 80% of the reperfused dogs treated with aspirin showed reocclusion, whereas none of them reoccluded when treated with Ro 43-5054. Thus, inhibition of platelet activation by the selective, nonpeptidic glycoprotein IIb-IIIa receptor antagonist Ro 43-5054, although without effect on the time to reperfusion, better protected than aspirin against early reocclusion after thrombolytic therapy.
Roux
S P
SP
Pharma Division, F. Hoffmann-La Roche, Ltd, Basel, Switzerland.
Tschopp
T B
TB
Kuhn
H
H
Steiner
B
B
Hadváry
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D003327:Coronary Disease / Q000188:drug therapy; D003331:Coronary Vessels; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D015425:Myocardial Reperfusion; D009842:Oligopeptides / Q000494:pharmacology*; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011817:Rabbits; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D009842:Oligopeptides; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011971:Receptors, Immunologic; C032193:glycoprotein receptor GPIb-IX; C078174:Ro 43-5054; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin