Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis

Circulation
P GolinoJ T Willerson

Abstract

Dynamic changes of the thrombus after its formation due to platelet activation may affect the speed of thrombolysis. In the present study, we wanted to evaluate the role played by thromboxane A2 (TXA2) and serotonin (5HT) in mediating platelet activation during lysis of intracoronary thrombi with human recombinant tissue-type plasminogen activator (t-PA). Coronary thrombi were induced in 26 anesthetized, open-chest dogs by inserting a copper coil into the left anterior descending coronary artery (LAD). LAD blood flow was monitored throughout the experiment by means of a Doppler flow probe placed proximally to the coil. Presence of the thrombus was documented for 30 minutes. The dogs were then assigned to one of four groups as follows: group 1 dogs (n = 8), serving as controls, received a bolus of heparin (200 units/kg) and a bolus of t-PA (80 micrograms/kg) followed by a continuous infusion (8 micrograms/kg/min) for up to 90 minutes or until reperfusion was achieved; group 2 dogs (n = 10) received, immediately before heparin and t-PA, an intravenous bolus of SQ29548 (SQ) (0.4 mg/kg, a selective TXA2-receptor antagonist) and LY53857 (LY) (0.2 mg/kg, a selective serotonin S2-receptor antagonist); group 3 dogs (n = 7) received, be...Continue Reading

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Citations

Sep 1, 1991·Medicinal Research Reviews·S E Hall
Feb 1, 1992·Cardiovascular Drugs and Therapy·J Vermylen, H Deckmyn
Jan 1, 1990·Journal of Tongji Medical University = Tong Ji Yi Ke Da Xue Xue Bao·H Y Zhao, W Y Fang
Jan 1, 1995·La Revue de médecine interne·G GrollierJ C Potier
Apr 1, 1990·Journal of the American College of Cardiology·E J Topol
Mar 1, 1991·Journal of the American College of Cardiology·J L MehtaT G Saldeen
Oct 17, 1991·The New England Journal of Medicine·J T Willerson, O H Frazier
Sep 2, 1993·The New England Journal of Medicine·H V Anderson, J T Willerson
Jan 20, 2004·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Antonio L Bartorelli
Jun 17, 2004·American Journal of Veterinary Research·Daniel F Hogan, Michael P Ward
Jan 1, 1991·The American Journal of the Medical Sciences·M S Runge
Sep 3, 1991·The American Journal of Cardiology·G A FitzGerald
May 1, 1992·Progress in Cardiovascular Diseases·J FareedR Pifarre
Jan 1, 1994·International Journal of Cardiology·P R BelcherM I Noble
Feb 2, 1990·The American Journal of Cardiology·J H ChesebroV Fuster
Jan 25, 1991·The American Journal of Cardiology·J T WillersonL M Buja

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