© 1993 by European Society of Cardiology
Copyright © 1993, European Society of Cardiology
Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery
University of Michigan Medical School, Ann Arbor, Michigan 48109-0626, USA – Department of Pharmacology: W E Rote, J H Davis, K S Kilgore, B R Lucchesi; Department of Internal Medicine, Division of Cardiology: S W Werns; G D Searle & Co, Skokie, IL, USA: L P Feigen.
Correspondence to Dr Lucchesi (M6322 Medical Science Building I).
Objective: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. Methods: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 µA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 µg·kg–1·min–1 intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. Results: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control=100%, n=12; SC 30 µg=50%, n=6; SC 60 µg=0%, n=6; p<0.05). SC resulted in a reduction in thrombus weight (p<0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U·kg–1). SC (60 µg·kg–1·min–1, intravenously, n=6) or saline (n=6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p<0.05). Conclusions: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor.
Cardiovascular Research 1993;27:500-507
KEYWORDS platelets; thrombolysis; rethrombosis; GPIIb/IIIa
This study was supported by a grant from the National Institutes of Health, Heart, Lung and Blood Institute, HL19782-14.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. Bednar and C. E. Gross Antiplatelet Therapy in Acute Cerebral Ischemia Stroke, April 1, 1999; 30(4): 887 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Rebello, J. Huang, K. Saito, and B. R. Lucchesi In Vivo Efficacy of SM-20302, a GP IIb/IIIa Receptor Antagonist, Correlates With Ex Vivo Platelet Inhibition in Heparinized Blood but Not in Citrated Blood Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 954 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Strony, A. Song, L. Rusterholtz, and B. Adelman Aurintricarboxylic Acid Prevents Acute Rethrombosis in a Canine Model of Arterial Thrombosis Arterioscler Thromb Vasc Biol, March 1, 1995; 15(3): 359 - 366. [Abstract] [Full Text]
|
|