Abstract
Under high shear arterial blood flow von Willebrand Factor (vWF) binds the platelet receptor glycoprotein (GP) Ibalpha, leading to platelet adhesion, activation and thrombosis. Blockade of vWF-GPIb alpha interactions by GPG-290 was investigated in a canine model of coronary artery thrombosis alone and in combination with clopidogrel. GPG-290 (100 microg/kg, n=6; 500 microg/kg, n=6) prolonged time to thrombotic occlusion (TTO) to 105+/-34 and 156+/-23 (p<0.05) min, respectively compared to the saline treated control group (32+/-6 min, n=6). Patency of the injured vessel was sustained in 1/6 (100 microg/kg) and 3/6 vessels (500 microg/kg) 4 hours after injury, in contrast to 0/6 in the control group. There was an increase in bleeding after the 500 microg/kg dose, but only at the 1 hr time point. Clopidogrel was studied in two dosing regimens representing either a clinical pretreatment regimen (PTR) of 4.3 mg/kg on day -2 followed by 1.1 mg/kg daily for 2 days prior to the procedure or pre-procedural loading dose regimen (LDR) of 4.3 mg/kg 3 hr pre-procedure. The PTR and LDR clopidogrel treatments prolonged TTO to 98.2+/-30.0 min and 136.1+/-39.5 min (p<0.05), and sustained patency in 1/6 and 4/8 vessels, respectively. However, te...Continue Reading
Citations
Aug 15, 2008·Cancer Research·Benoit Ho-Tin-NoéDenisa D Wagner
Nov 21, 2007·Circulation·James C GilbertRobert G Schaub
Sep 23, 2008·Blood·Augusto B FedericiPhilip G De Groot
Mar 13, 2016·Journal of Veterinary Pharmacology and Therapeutics·J ThomasonA Mackin
May 21, 2017·Journal of Hematology & Oncology·Shundong JiYiming Zhao
Oct 21, 2010·Blood·Alexander BrillDenisa D Wagner
Jul 25, 2009·Journal of Thrombosis and Haemostasis : JTH·T SzantoJ Harsfalvi
Jan 12, 2013·Journal of Cardiovascular Translational Research·Jozef BartunekJosefin-Beate Holz
Nov 27, 2010·Expert Review of Cardiovascular Therapy·Christa FirbasBernd Jilma
Jun 16, 2012·Expert Review of Clinical Pharmacology·Kallirroi I KalantziAlexandros D Tselepis
Jan 18, 2019·Journal of Veterinary Emergency and Critical Care·Robert GoggsRonald H L Li
Sep 26, 2019·Current Pharmaceutical Design·Vivek K YadavSunil K Singh
Sep 18, 2007·Expert Review of Cardiovascular Therapy·Gregory DucrocqJean-Francois Tanguay
May 18, 2011·Blood·Hans UlrichtsJosefin-Beate Holz
Mar 19, 2013·Future Medicinal Chemistry·Jens Minnerup, Christoph Kleinschnitz
Dec 20, 2011·Stroke; a Journal of Cerebral Circulation·Simon F De MeyerChristoph Kleinschnitz
Oct 22, 2016·Thrombosis Journal·Xiaohong Ruby XuHeyu Ni
Jan 18, 2019·Journal of Veterinary Emergency and Critical Care·Robert GoggsClaire R Sharp
May 9, 2009·Journal of Thrombosis and Haemostasis : JTH·J L DienerR Schaub
Jan 18, 2019·Journal of Veterinary Emergency and Critical Care·Marie-Claude BlaisClaire R Sharp
Aug 2, 2018·Cancers·Annalisa BrunoPaola Patrignani
May 12, 2009·Journal of Thrombosis and Haemostasis : JTH·M Laffan, T A J McKinnon
Mar 28, 2008·Biochemistry·Susan Adam BenardKerry S Kelleher
Sep 4, 2021·Pharmacotherapy·Bo ZhengYong Huo