Zurbano M J, Heras M, Rigol M, Roig E, Epelde F, Miranda F, Sanz G, Escolar G, Ordinas A
Servicio de Hemoterapia y Hemostasia, Hospital Clínico y Provincial de Barcelona, Spain.
Eur J Clin Invest. 1997 Feb;27(2):116-20. doi: 10.1046/j.1365-2362.1997.680633.x.
Myocardial infarction in cocaine abusers may be related to a direct platelet-activating effect. We analysed this possibility in an experimental model. Studies were carried out in eight normal, anaesthetized pigs with a weight of 30.7 +/- 3.7 kg. Blood samples were withdrawn before and 20 min after i.v. administration of cocaine (10 mg kg-1; at 1 mg kg-1 every 2 min). Modifications in platelet responses to arachidonic acid (AA; 1.4 mmol L-1), ADP (1-4 microM), synthetic thromboxane endoperoxide analogue (U46619; 1 microM), collagen (2.5-5 micrograms mL-1), adrenaline (10 microM) and ristocetin (0.8-1 mg mL-1) were tested by conventional aggregometry. Changes in the capacity of platelets to form aggregates on damaged subendothelium were assessed by means of an ex vivo perfusion system in which blood was circulated for 10 min at 800 s-1, a shear rate similar to that found in normal coronary arteries. The interaction of platelets with perfused denuded arterial segments was morphometrically quantified and expressed as a percentage of damaged vessel surface covered by platelets (%CS). Cocaine administration did not influence platelet aggregation patterns in pigs. However, there was a significant increase in the interaction of pig platelets with subendothelial structures after cocaine infusion (%CS = 40 +/- 17% vs. 27 +/- 16% baseline; mean +/- SD; P < 0.01). Cocaine administration in this animal model increases the reactivity of platelets exposed to subendothelium. These results support the concept that the administration of cocaine to pigs has a prothrombotic effect by facilitating the interaction of platelets with damaged arteries.
可卡因滥用者发生心肌梗死可能与血小板直接激活作用有关。我们在一个实验模型中分析了这种可能性。对8只体重为30.7±3.7千克的正常麻醉猪进行了研究。在静脉注射可卡因（10毫克/千克；每2分钟注射1毫克/千克）前及注射后20分钟采集血样。通过传统的血小板聚集测定法检测血小板对花生四烯酸（AA；1.4毫摩尔/升）、二磷酸腺苷（ADP；1 - 4微摩尔）、合成血栓素内过氧化物类似物（U46619；1微摩尔）、胶原（2.5 - 5微克/毫升）、肾上腺素（10微摩尔）和瑞斯托霉素（0.8 - 1毫克/毫升）反应的变化。通过体外灌注系统评估血小板在受损内皮下形成聚集体的能力，在该系统中血液以800秒-1的流速循环10分钟，这一剪切速率与正常冠状动脉中的剪切速率相似。对血小板与灌注的剥脱动脉段的相互作用进行形态计量学定量，并表示为血小板覆盖的受损血管表面的百分比（%CS）。给予可卡因对猪的血小板聚集模式没有影响。然而，输注可卡因后猪血小板与内皮下结构的相互作用显著增加（%CS = 40±17% 对比基线时的27±16%；平均值±标准差；P < 0.01）。在该动物模型中给予可卡因会增加暴露于内皮下的血小板的反应性。这些结果支持这样的概念，即给猪施用可卡因通过促进血小板与受损动脉的相互作用而具有促血栓形成作用。
