Abstract 5940: Central Sympatholysis With Dexmedetomidine is an Effective Countermeasure for Cocaine-Induced Sympathetic Activation and Peripheral Vasoconstriction in Chronic Cocaine Abusers
Cocaine has been shown to stimulate the human cardiovascular system by acting primarily in the brain to increase sympathetic nerve activity to the peripheral circulation. In healthy cocaine naïve subjects, we previously showed that central sympatholysis with an α2 adrenoreceptor (AR) agonist, dexmedetomidine, is an effective strategy in reversing cocaine-induced sympathetic activation and peripheral vasoconstriction. However, in animal experiments, chronic cocaine exposure causes desensitization of central α2 adrenoreceptors. Whether central α2 agonists remain effective in reversing the sympathoexcitatory action of cocaine in chronic cocaine abusers is unknown. Accordingly, in 20 chronic cocaine abusers with an average history of cocaine use of 19±2 years, we measured skin SNA (microneurography), skin blood flow (laser flow velocimetry), as well as heart rate (HR) and mean arterial pressure (MAP) at baseline, after intranasal cocaine (3mg/kg) alone and in combination with dexmedetomidine or saline. During intranasal cocaine, skin SNA increased by 2 fold (p < 0.01), skin vascular resistance increased from 20.94±3.78 to 25.49±4.36 resistance units (p ≤ 0.01) and rate pressure product increased from 7,912±452 to 10, 247±949 mmHg. beats/min (p ≤ 0.01). Dexmedetomidine reversed these increases, whereas saline was without effect. To determine if central α2 AR sensitivity is altered by chronic cocaine exposure, we measured muscle SNA, MAP, HR, and plasma norepinephrine levels during graded intravenous infusion of dexmedeto-midine (0.1, 0.2, and 0.3 mcg/kg) in 7 chronic cocaine abusers and 5 healthy cocaine-naive controls matched for age, gender, and ethnicity. Dexmedetomidine caused similar dose-dependent reductions in muscle SNA, blood pressure and plasma norepinephrine in both groups. We conclude that (1) chronic cocaine abusers display normal sympathoinhibitory responses to a central α2 agonist, and (2) central sympatholysis with dexmedetomidine remains an effective countermeasure for cocaine-induced sympathetic activation in chronic cocaine abusers.