Human Platelet Ca 2+ Mobilization, Glycoprotein IIb/IIIa Activation, and Experimental Coronary Thrombosis In Vivo in Dogs Are All Inhibited by the Inotropic Agent Amrinone
| Autor: | C. Uhl, J. C. Sill, I. Berger, B. G. Bertha, John D. Folts, M. Nugent |
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| Rok vydání: | 1997 |
| Předmět: |
Blood Platelets
Inotrope Cardiotonic Agents Epinephrine Vasodilator Agents Pharmacology Amrinone Coronary circulation Dogs Coronary thrombosis In vivo Coronary Circulation Physiology (medical) Animals Humans Medicine Platelet business.industry Coronary Thrombosis Biological Transport P-Selectin medicine.anatomical_structure Platelet Glycoprotein GPIb-IX Complex Anesthesia Calcium Cardiology and Cardiovascular Medicine business Glycoprotein IIb/IIIa Ex vivo medicine.drug |
| Zdroj: | Circulation. 96:1647-1653 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.96.5.1647 |
| Popis: | Background Inotropic drugs are often used to treat acute, severe heart failure resulting from acute myocardial infarction and other unstable coronary artery syndromes. However, catecholamine inotropic agents may potentiate coronary thrombosis via a platelet α 2 -adrenergic mechanism, thus exacerbating the original problem. The present studies were designed to determine whether the nonadrenergic inotropic and vasodilator drug amrinone, which elevates platelet cAMP levels, would both inhibit human platelet Ca 2+ mobilization and adhesion molecule expression ex vivo and protect against experimental coronary thrombosis in vivo in dogs. Methods and Results Human platelets in suspension were preincubated with amrinone 2.5 to 15 μg/mL; stimulated with the agonists thrombin 0.1 U/mL, ADP 10 −6 mol/L, or arginine vasopressin 10 −7 mol/L; and studied for Ca 2+ mobilization, glycoprotein IIb/IIIa activation, and P-selectin expression by fluorescent flow cytometry methods. Experimental coronary thrombosis in vivo was studied in an open-chest dog model with critical coronary artery stenosis and deep vessel wall injury. Results showed that at the cellular level, amrinone inhibited agonist-induced Ca 2+ mobilization and had modest inhibitory effects on adhesion molecule expression. In vivo in dogs, intravenous amrinone 2 mg/kg plus infusion at 20 μg·kg −1 ·min −1 completely abolished coronary thrombosis. Conclusions The fact that amrinone inhibited human platelet activation at the cellular level and protected against experimental coronary thrombosis in vivo in dogs suggests a potentially advantageous antithrombotic action for this inotropic and vasodilator drug. |
| Databáze: | OpenAIRE |
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