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Revista chilena de cardiología

On-line version ISSN 0718-8560

Abstract

PEREIRA, Jaime et al. Endothelial damage and activation of the haemostatic system associated to chronic use of cocaine: an ex vivo and in vitro study. Rev Chil Cardiol [online]. 2010, vol.29, n.1, pp.37-46. ISSN 0718-8560.  http://dx.doi.org/10.4067/S0718-85602010000100004.

Background: chronic cocaine users have an increased risk of developing myocardial infarction, angina, sudden death and stroke. Although the pathogenesis of this effect is not completely known, premature atheromatosis and intravascular thrombosis appear to be involved. Aim: to provide evidence for the presence of endothelial damage and activation of the haemostatic system in chronic cocaine users. Methods: 23 subjects (19males, overall mean age 32) with DSM-IV criteria for cocaine dependency and exposure to the drug within 72 hours were studied. Endothelial dysfunction was determined by circulating endothelial cell counts (CEC) and sICAM levels. Thrombin-antithrombin complexes (TAT) and thrombin generation were used to characterize haemostatic status. In vitro, platelet activation was studied by NAP-2 and RANTES. EC in culture (HUVEC) were exposed to plasma from cocaine users and controls. Von Willebrand factor was measured in the culture media as well as its expression along with that of tissue factor in EC. Platelet adhesion was evaluated by microscopy. Results: Compared to controls, EC were significantly increased in cocaine users (63±28 vs. 7±5 cells per mL, p<0. 0001). Respective sICAM levels were 360±92 vs. 261 ±34 ng/mL (p<0. 01). Similarly TAT were 2. 7±0. 7 and 0. 7±0. 4µg/L, (p<0. 06). Similar findings were obtained for NAP (129±8. 4 vs. 87. 1 ±8. 6 ng/mL) and RANTES (4. 01 ±2. 12 vs. 2. 12±0. 35 ng/L) (p<0. 01). Plasma from cocaine users induced an increased liberation of vW factor from HUVEC compared to control (5. 64±4. 0 vs. 1. 4±0. 8 UI/dL; p ≤ 0. 001). HUVEC exposed to plasma from cocaine users expressed more FT and vW factor and had a greater capacity to induce platelet adhesion. Conclusion: endothelial dysfunction and activation of the haemostatic system is observed in cocaine users. Along with the observed in vitro effect of plasma from cocaine users upon EC, these results suggest a significant role of athero-thrombosis in the vascular damage associated to cocaine use.

Keywords : Endothelial dysfunction; haemostatic system; cocaine abuse.

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