Objectives: 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 toxicity 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-labeled 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 (30 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.