Mickelson J K, Hoff P T, Homeister J W, Fantone J C, Lucchesi B R
Department of Internal Medicine (Cardiology), University of Michigan School of Medicine, Ann Arbor.
J Am Coll Cardiol. 1993 Feb;21(2):502-10. doi: 10.1016/0735-1097(93)90695-w.
The purpose of this study was to assess the anti-thrombotic potential of various forms of aspirin administration.
Platelet activation in response to endothelial injury has been implicated in acute coronary syndromes.
Delivering 100-microA anodal direct current to the intima of the left circumflex coronary artery in dogs at a site of moderate external stenosis provides a thrombogenic model of vascular injury. Animals were treated with aspirin (Group I, 20 mg/kg intravenously [n = 11]; Group II, 4.6 mg/kg intravenously [n = 6]; Group III, 4.6 mg/kg orally 18 h before the experiment [n = 7]) or vehicle (Group IV, control [n = 11]).
The time required for thrombotic occlusion to occur was longer and the incidence of thrombosis was lower in Group I (Group I, 238 +/- 7 min [n = 2]; Group II, 127 +/- 25 min [n = 3]; Group III, 156 +/- 35 min [n = 6]; Group IV, 90 +/- 11 min [n = 11]) (p < 0.05). Thrombus mass was smaller in Group I (Group I, 5.0 +/- 0.8 mg; Group II, 12.2 +/- 2.6 mg; Group III, 11.6 +/- 3.9 mg; Group IV, 9.1 +/- 1.6 mg) (p < 0.05). Initial hemodynamic variables did not differ among groups. An increase in mean arterial pressure was noted for several hours after intravenous aspirin administration in Group I (99 +/- 5 to 110 +/- 4 mm Hg) (p < 0.05). Left circumflex coronary artery blood flow was stable for 5 h in Group I (Group I, 31 +/- 2 to 26 +/- 4 ml/min) but decreased in all the other groups (Group II, 26 +/- 4 to 10 +/- 5 ml/min; Group III, 27 +/- 5 to 7 +/- 7 ml/min; Group IV, 29 +/- 4 to 0 ml/min) (p < or = 0.05). The in vivo area of left ventricle perfused by the left circumflex coronary artery was not different among groups. Platelet counts were similar and did not change over the course of the protocol. Ex vivo arachidonic acid-induced platelet aggregation decreased in all groups after aspirin (p < or = 0.001). Indium-111-labeled platelet adherence to the coronary vasculature was decreased in distal vessel segments after all doses of aspirin (p < 0.05). Platelet deposition in thrombi was similar for all treatment groups.
High dose intravenous aspirin has salutary effects. It stabilizes left circumflex coronary artery blood flow, prolongs the time to thrombosis, reduces the incidence of thrombotic occlusion, reduces thrombus mass and limits platelet adherence to sites of arterial injury. Low dose aspirin given intravenously or orally was ineffective. When persistent intracoronary thrombi precipitate unstable coronary syndromes, high dose intravenous aspirin may be useful in the acute period even though platelets continue to interact with injured vascular segments through aspirin-insensitive mechanisms.
本研究旨在评估不同给药方式的阿司匹林的抗血栓形成潜力。
对内皮损伤作出反应的血小板激活与急性冠状动脉综合征有关。
在中度外部狭窄部位向犬的左旋冠状动脉内膜施加100微安阳极直流电，可建立血管损伤的血栓形成模型。动物接受阿司匹林治疗（第一组，静脉注射20毫克/千克[n = 11]；第二组，静脉注射4.6毫克/千克[n = 6]；第三组，在实验前18小时口服4.6毫克/千克[n = 7]）或赋形剂（第四组，对照组[n = 11]）。
第一组发生血栓闭塞所需时间更长，血栓形成发生率更低（第一组，238±7分钟[n = 2]；第二组，127±25分钟[n = 3]；第三组，156±35分钟[n = 6]；第四组，90±11分钟[n = 11]）（p < 0.05）。第一组的血栓质量更小（第一组，5.0±0.8毫克；第二组，12.2±2.6毫克；第三组，11.6±3.9毫克；第四组，9.1±1.6毫克）（p < 0.05）。各组初始血流动力学变量无差异。第一组静脉注射阿司匹林后数小时平均动脉压升高（99±5至110±4毫米汞柱）（p < 0.05）。第一组左旋冠状动脉血流在5小时内保持稳定（第一组，31±2至26±4毫升/分钟），但其他所有组均下降（第二组，26±4至10±5毫升/分钟；第三组，27±5至7±7毫升/分钟；第四组，29±4至0毫升/分钟）（p≤0.05）。左旋冠状动脉灌注的左心室体内面积在各组间无差异。血小板计数相似，且在实验过程中未发生变化。阿司匹林后所有组的体外花生四烯酸诱导的血小板聚集均降低（p≤0.001）。所有剂量的阿司匹林后，远端血管段中铟-111标记的血小板对冠状血管的黏附均降低（p < 0.05）。所有治疗组血栓中的血小板沉积相似。
高剂量静脉注射阿司匹林有有益作用。它可稳定左旋冠状动脉血流，延长血栓形成时间，降低血栓闭塞发生率，减少血栓质量，并限制血小板黏附于动脉损伤部位。静脉或口服低剂量阿司匹林无效。当持续性冠状动脉内血栓引发不稳定冠状动脉综合征时，即使血小板通过阿司匹林不敏感机制继续与受损血管段相互作用，高剂量静脉注射阿司匹林在急性期可能仍有用。
