title: 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.
abstract: 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.
authors.affiliation: Pharma Division, F. Hoffmann-La Roche, Ltd, Basel, Switzerland.
authors.forename: S P
authors.initials: SP
authors.lastname: Roux
authors.forename: T B
authors.initials: TB
authors.lastname: Tschopp
authors.forename: H
authors.initials: H
authors.lastname: Kuhn
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: P
authors.initials: P
authors.lastname: Hadváry
mesh_terms: 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*
chemical_list: 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