COCAINE ADMINISTRATION ENHANCES PLATELET REACTIVITY TO SUBENDOTHELIALCOMPONENTS - STUDIES IN A PIG MODEL

Myocardial infarction in cocaine abusers may be related to a direct pl atelet-activating effect. We analysed this possibility in an experimen tal model. Studies were carried out in eight normal, anaesthetized pig s 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 Blood samples were withdrawn before and 20 min after i.v. administration of cocaine (10 mg kg(-1); at 1 mg kg(-1) every 2 min).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 arachidon ic acid (AA; 1.4 mmol L(-1)), ADP (1-4 mu M), synthetic thromboxane en doperoxide analogue (U46619; 1 mu M), collagen (2.5-5 mu g mL(-1)), ad renaline (10 mu M) and ristocetin (0.8-mg mL(-1)) were tested by conve ntional aggregometry. Changes in the capacity of platelets to farm agg regates 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 v essel surface covered by platelets (%CS). Cocaine administration did n ot influence platelet aggregation patterns in pigs. However, there was a significant increase in the interaction of pig platelets with suben dothelial 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.