Cocaine administration enhances platelet reactivity to subendothelial components: studies in a pig model.
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 Blood samples were withdrawn before and 20 min after i.v. administration of cocaine (10 mg kg-1; at 1 mg kg-1 every 2 min).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.
Zurbano
M J
MJ
Servicio de Hemoterapia y Hemostasia, Hospital Clínico y Provincial de Barcelona, Spain.
Heras
M
M
Rigol
M
M
Roig
E
E
Epelde
F
F
Miranda
F
F
Sanz
G
G
Escolar
G
G
Ordinas
A
A
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013552:Swine
D016718:Arachidonic Acid; D003042:Cocaine; D004837:Epinephrine