EFFECTS OF ACTIVE CHRONIC COCAINE USE ON CARDIAC SYMPATHETIC NEURONALFUNCTION ASSESSED BY CARBON-11-HYDROXYEPHEDRINE

Cardiac toxicity of cocaine has been linked to its inhibitory effect o n norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has bee n validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible i n vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals, The aim of the study was to use the catecholamine analog C-11-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifi es the function of sympathetic nerve terminals of the heart. Methods: Six normal female volunteers and nine female active chronic cocaine us ers were studied, Cardiac regional C-11-hydroxyephedrine uptake and bl ood flow, as assessed with N-13-ammonia, were determined using semiqua ntitative polar map analysis of myocardial tracer distribution. Carbon -11-hydroxyephedrine cardiac retention was quantified using dynamic da ta acquisition and kinetic analysis of blood and tissue activity. Resu lts: Active chronic cocaine users showed small areas of abnormal blood flow and C-11-hydroxyephedrine retention in the heart in comparison w ith normal volunteers. The extent of abnormalities expressed as a perc ent of the total polar map area averaged 2.0% +/- 2.6% and 2.5% +/- 2. 7% for blood flow and C-11-hydroxyephedrine uptake, respectively. Myoc ardial C-11-hydroxyephedrine retention was significantly reduced by 22 % in active cocaine users (0.109 +/- 0.017 min(-1)), as compared to no rmal controls (0.140 +/- 0.027 min(-1)). Conclusion: PET imaging with C-11-hydroxyephedrine permits quantitative assessment of cardiac norep inephrine transporter function in active chronic cocaine users. The re sults of this study suggest prolonged reduction of norepinephrine upta ke and storage capacity in the cardiac sympathetic nerve terminals whi ch may reflect the effect of repetitive elevation of norepinephrine le vels induced by cocaine exposure.