title: Imaging of cardiac neuronal function after cocaine exposure using carbon-11 hydroxyephedrine and positron emission tomography.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
authors.forename: P G
authors.initials: PG
authors.lastname: Melon
authors.forename: N
authors.initials: N
authors.lastname: Nguyen
authors.forename: T R
authors.initials: TR
authors.lastname: DeGrado
authors.forename: T J
authors.initials: TJ
authors.lastname: Mangner
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
authors.forename: M
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: C065363:3-hydroxyephedrine; D004809:Ephedrine; D003042:Cocaine