Sill J C, Bertha B, Berger I, Uhl C, Nugent M, Folts J
Department of Anesthesiology, Mayo Clinic, Rochester, Minn 55905, USA.
Circulation. 1997 Sep 2;96(5):1647-53. doi: 10.1161/01.cir.96.5.1647.
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 alpha2-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 Ca2+ mobilization and adhesion molecule expression ex vivo and protect against experimental coronary thrombosis in vivo in dogs.
Human platelets in suspension were preincubated with amrinone 2.5 to 15 microg/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 Ca2+ 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 Ca2+ mobilization and had modest inhibitory effects on adhesion molecule expression. In vivo in dogs, intravenous amrinone 2 mg/kg plus infusion at 20 microg x kg(1) x min(-1) completely abolished coronary thrombosis.
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.
正性肌力药物常用于治疗由急性心肌梗死和其他不稳定冠状动脉综合征引起的急性、严重心力衰竭。然而，儿茶酚胺类正性肌力药物可能通过血小板α2 - 肾上腺素能机制增强冠状动脉血栓形成，从而使原问题恶化。本研究旨在确定非肾上腺素能正性肌力和血管扩张药物氨力农（可提高血小板环磷酸腺苷水平）是否既能在体外抑制人血小板Ca2+动员和黏附分子表达，又能在体内保护犬免受实验性冠状动脉血栓形成。
将悬浮的人血小板与2.5至15微克/毫升的氨力农预孵育；用0.1单位/毫升凝血酶、10(-6)摩尔/升二磷酸腺苷或10(7)摩尔/升精氨酸加压素刺激；并通过荧光流式细胞术方法研究Ca2+动员、糖蛋白IIb/IIIa激活和P - 选择素表达。在具有严重冠状动脉狭窄和深部血管壁损伤的开胸犬模型中研究体内实验性冠状动脉血栓形成。结果表明，在细胞水平上，氨力农抑制激动剂诱导的Ca2+动员，并对黏附分子表达有适度的抑制作用。在犬体内，静脉注射2毫克/千克氨力农并以20微克·千克(1)·分钟(-1)输注可完全消除冠状动脉血栓形成。
氨力农在细胞水平上抑制人血小板活化并在犬体内保护其免受实验性冠状动脉血栓形成，这一事实表明这种正性肌力和血管扩张药物具有潜在的有利抗血栓作用。
