IMAGING OF CARDIAC NEURONAL FUNCTION AFTER COCAINE EXPOSURE USING C-11 HYDROXYEPHEDRINE AND POSITRON EMISSION TOMOGRAPHY

Objectives. The aim of the study was to define the effect of cocaine o n the myocardial uptake and retention of C-11 hydroxyephedrine in the anesthetized dog model. Background. Cardiac toxicity of cocaine has be en linked to its inhibitory effect on norepinephrine reuptake by the s ympathetic nerve terminals of the heart. Carbon-11 hydroxyephedrine is a C-11-labeled norepinephrine analog that has high specific affinity for uptake-1 and thus makes possible the assessment of the effect of c ocaine on norepinephrine reuptake by cardiac sympathetic nerve termina ls. Methods. The cardiac kinetics of C-11 hydroxyephedrine as assessed by dynamic positron emission tomographic imaging were used to charact erize norepinephrine reuptake by the sympathetic nerve terminals. Carb on-11 hydroxyephedrine was injected intravenously before, as well as a t 5 min and 2.5 h after, intravenous administration of 2 mg/kg body we ight of cocaine in anesthetized dogs. Hemodynamic variables and micros phere determined cardiac blood flow were also measured before and afte r cocaine exposure. Results. Intravenous injection of cocaine did not significantly affect hemodynamic variables and myocardial blood flaw i n the anesthetized animals. Compared with baseline, myocardial retenti on of C-11 hydroxyephedrine was significantly reduced by 78 +/- 3% (me an +/- SD) at 5 min and remained significantly reduced (28 +/- 17%) at 2.5 h after cocaine injection. Cocaine administration after C-11 hydr oxyephedrine injection (30 min) resulted in rapid biexponential cleara nce of C-11 hydroxyephedrine from myocardium. Conclusions. These resul ts suggest prolonged effects of cocaine on the sympathetic nerve termi nals of the heart. Positron emission tomography provides a noninvasive and sensitive means to objectively assess the cardiac pharmacokinetic s of drugs such as cocaine.