Changes in regional cerebral blood flow are associated with endothelial dysfunction markers in cocaine-dependent patients under recent abstinence.

OBJECTIVES: Cocaine is a known risk factor for several vascular ischemic events. The underlying mechanisms leading to the complications are not fully understood, although thrombus formation and accelerated atherosclerosis are prominent findings. Evidence of endothelial dysfunction (ED), a key phenomenon in the pathogenesis of atherogenesis, has been demonstrated in cocaine-dependent individuals. Abnormal regional cerebral blood flow (rCBF) is a common finding among chronic cocaine users. The aim of this study was to evaluate whether brain perfusion changes were associated with ED markers in cocaine-dependent individuals. METHODS: Circulating endothelial cells (CECs), soluble intercellular cell adhesion molecule, and the chemokine regulated on activation normal T cells expressed and secreted were measured in 27 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) cocaine-dependents patients. Regional cerebral blood flow was assessed using single-photon emission computed tomography at baseline (after recent cocaine consumption) and after 4 weeks of strict abstinence under standard benzodiazepine or antipsychotic therapy. We used statistical parametric mapping analysis to evaluate the covariates. RESULTS: Endothelial cell damage/activation markers were significantly higher in cocaine-dependent individuals after recent consumption and were reduced after 1-month abstinence (P < 0.05). Global rCBF exhibited no significant difference between baseline and after abstinence. When regional perfusion was analyzed in association with ED covariates, significant differences were observed in bilateral cortical areas, including the limbic lobes. CONCLUSIONS: We demonstrated an association between systemic ED markers and rCBF in cocaine-dependent patients. These findings suggest that vascular injury may play a role in the pathogenesis of abnormal rCBF.

Platelet activation in chronic cocaine users: effect of short term abstinence.

Cocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers. We studied 23 cocaine dependent individuals (aged 20-54 years) who met DSM-IV criteria for cocaine dependence and 20 controls. Samples were obtained at baseline, within 72 h of last drug exposure and after 4 weeks of controlled abstinence. Monocyte-platelet aggregates (MPA) were measured by flow cytometry. Plasma levels of soluble CD40L (sCD40L), Neutrophil-Activating Peptide-2 (NAP-2) and regulated on activation normal T cells expressed and secreted (RANTES) were determined by ELISA. Levels of MPA, sCD40L, NAP-2 and RANTES were significantly higher (all p < 0.05) in cocaine addicts compared to controls at baseline. All the parameters returned to values similar to the control group after 4-weeks' abstinence. Levels of sCD40L and RANTES were associated with an index of intensity of drug consumption (p < 0.02). Our results demonstrate that cocaine use induces platelet activation which is a prominent finding after recent consumption. The persistence over time of this condition may contribute not only to acute thrombotic complications but also to the development of early-onset atherosclerotic process observed in cocaine abusers.