Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation

J Am Coll Cardiol. 1990 Sep;16(3):714-22. doi: 10.1016/0735-1097(90)90364-u.

Abstract

The comparative effects of intravenous aspirin, the synthetic thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (Argatroban) and F(ab')2 fragments of monoclonal antibody 7E3 against platelet glycoprotein IIb/IIIa (7E3-F[ab']2) on thrombolysis, reocclusion and bleeding associated with 0.45 mg/kg body weight bolus injections of recombinant tissue-type plasminogen activator (rt-PA) were studied in a canine coronary artery thrombosis model. Coronary patency was monitored for 2 h both by flow probe and by coronary angiography. Four groups were studied: Group I = pretreated with 17 mg/kg intravenous aspirin (n = 6), Group II = pretreated with 200 micrograms/kg per min intravenous Argatroban for 60 min (n = 5), Group III = pretreated with aspirin and Argatroban (n = 5) and Group IV = pretreated with 0.8 mg/kg intravenous 7E3-F(ab')2 (n = 5). In Group I, reflow occurred in four of six dogs, but did not persist; reflow was induced in Group II in four of five dogs, persisting in one; in Group III, reflow occurred in all five dogs, persisting in four; in Group IV reflow was achieved in four of five dogs, persisting in two. The frequency of persistent reflow in Group III was significantly higher than in the combined Groups I and II (p = 0.012), whereas the time to reflow was significantly shorter in the groups receiving Argatroban than in the aspirin group (median 25 versus 55 min, p = 0.04). There were no significant differences between Groups III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antithrombins / therapeutic use*
  • Arginine / analogs & derivatives
  • Aspirin / therapeutic use*
  • Coronary Circulation
  • Coronary Disease / drug therapy*
  • Coronary Thrombosis / drug therapy*
  • Dogs
  • Pipecolic Acids / therapeutic use*
  • Platelet Membrane Glycoproteins / immunology*
  • Recurrence
  • Sulfonamides
  • Thrombolytic Therapy*
  • Tissue Plasminogen Activator / therapeutic use*
  • Vascular Patency

Substances

  • Antibodies, Monoclonal
  • Antithrombins
  • Pipecolic Acids
  • Platelet Membrane Glycoproteins
  • Sulfonamides
  • Arginine
  • Tissue Plasminogen Activator
  • argatroban
  • Aspirin