Imaging of cardiac neuronal function after cocaine exposure using Carbon-11 hydroxyephedrine and positron emission tomography

AbstractObjectives. The aim of the study was to define the effect of cocaine on the myocardial uptake and retention of C-11 hydroxyephedrine in the anesthetized dog model.Background. Cardiac toxcity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by the sympathetic nerve terminals of the heart. Carbon-11 hydroxyephedrine is a C-11-labled norepinephrine analog that has high specific affinity for uptake-1 and thus makes possible the assessment of the effect of cocaine on norepinephrine reuptake by cardiac sympathetic nerve terminals.Methods. The cardiac kinetics of C-11 hydroxyephedrine as assessed by dynamic positron emission tomographic imaging were used to characterize norepinephrine reuptake by the sympathetic nerve terminals. Carbon-11 hydroxyephedrine was injected intravenously before, as well as at 5 min and 2.5 h after, intravenous administration of 2 mg/kg body weight of cocaine in anesthetized dogs. Hemodynamic variables and microsphere-determined cardiac blood flow were also measured before and after cocaine exposure.Results. Intravenous injection of cocaine did not significantly affect hemodynamic variables and myocardial blood flow in the anesthetized animals. Compared with baseline, myocardial retention of C-11 hydroxyephedrine was significantly reduced by 78 ± 3% (mean ± SD) at 5 min and remained significantly reduced (28 ± 17%) at 2.5 h after cocaine injection. Cocaine administration after C-11 hydroxyephedrine injection (39 min) resulted in rapid biexponential clearance of C-11 hydroxyephedrine from myocardium.Conclusions. These results suggest prolonged effects of cocaine on the sympathetic nerve terminals of the heart. Positron emission tomography provides a noninvasive and sensitive means to objectively assess the cardiac pharmacokinetics of drugs such as cocaine