Effects of a novel platelet nitric oxide donor (LA816), aspirin, clopidogrel, and combined therapy in inhibiting flow- and lesion-dependent thrombosis in the porcine ex vivo model

Circulation
Gemma VilahurL Badimon

Abstract

Acetylsalicylic acid (ASA), or aspirin, plus clopidogrel is becoming the standard antithrombotic treatment in people with coronary disease. Novel approaches such as the use of platelet-selective nitric oxide (NO) donors may provide additional protection against thrombosis. We evaluated the antithrombotic properties of a novel platelet-selective NO donor (LA816) administered alone and in combination with ASA, clopidogrel, or ASA+clopidogrel. Thrombogenicity was measured in the porcine experimental model and assessed as platelet-thrombus formation in the ex vivo Badimon perfusion chamber. Pigs were randomly divided into 4 groups: (1) placebo control, (2) clopidogrel, (3) ASA, and (4) ASA+clopidogrel (ASA and clopidogrel were given orally, 10 mg x kg(-1) x d(-1) for 3 d). The animals were anesthetized, heparinized, and catheterized, and the Badimon perfusion chamber was placed in an extracorporeal shunt. After baseline perfusions, all animal groups received the intravenous infusion of LA816 for 2 hours. Platelet aggregation, blood pressure, and heart rate also were evaluated during the experiments. LA816, clopidogrel, and ASA+clopidogrel produced a reduction of approximately 45% on thrombus mass versus placebo control perfusions (...Continue Reading

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Citations

Sep 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nicholas S KirkbyTimothy D Warner
Jun 12, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·F Javier García-CriadoJosé M López-Novoa
Jan 16, 2014·Annual Review of Medicine·A Phillip Owens, Nigel Mackman
Jan 29, 2011·Journal of Biomedicine & Biotechnology·Gemma VilahurLina Badimon
May 9, 2008·Revista española de cardiología·Lina Badimon, Gemma Vilahur
Apr 30, 2005·European Journal of Clinical Investigation·M R HernandezG Escolar
Dec 15, 2010·Journal of Thrombosis and Haemostasis : JTH·P C J ArmstrongT D Warner
Oct 15, 2013·Journal of Thrombosis and Haemostasis : JTH·R de la TorreL Badimon
Apr 2, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jung-Jin LeeJin Yeul Ma
Jul 19, 2005·Expert Opinion on Investigational Drugs·Roberto ScatenaBruno Giardina
Sep 14, 2014·European Heart Journal·Ilaria RamaiolaLina Badimon
Feb 15, 2020·Journal of the American College of Cardiology·Usman BaberJuan J Badimon

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