title: Myocardial kinetics of carbon-11-epinephrine in the isolated working rat heart.
abstract: The kinetics of EPI were studied in the isolated rat heart model to evaluate 11C-epinephrine (EPI) as a radiotracer for the assessment of sympathetic neuronal function in the heart.
  
  
  METHODS
  Isolated rat hearts were perfused in a working mode. Carbon-11-EPI was added to the perfusate during wash-in period of 20 min, followed by a washout period of 40 min. Radioactivity in the heart was externally monitored and time-activity curves were recorded as a function of time. Effluent samples were collected throughout each study to determine the fraction of 11C radioactivity as intact tracer.
  
  
  RESULTS
  Time-activity curves of control hearts showed that 11C-EPI is taken up and retained by the myocardium. Desipramine inhibition (DMI) of uptake-1 resulted in a significant decrease in myocardial uptake and retention of 11C-EPI by 91% compared to controls. Addition of DMI to the perfusion medium during washout did not affect kinetics of 11C-EPI compared to control hearts. Reserpine pretreated rat hearts also showed significant decrease in tracer retention of 95% compared to controls. The metabolic data showed that, in control conditions, about 61% of 11C-EPI taken up by the rat heart is rapidly metabolized and released.
  
  
  CONCLUSIONS
  Carbon-11-EPI traces sympathetic nerve terminals in the isolated rat heart. Uptake blockade by DMI and reserpine suggest that uptake and storage of 11C-EPI appear to be similar to that of norepinephrine. However, the prominent metabolic pathway warrants further consideration. These results suggest that 11C-EPI may be a suitable radiolabeled tracer for the evaluation of sympathetic vesicular function of the heart by PET.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: N T
authors.initials: NT
authors.lastname: Nguyen
authors.forename: T R
authors.initials: TR
authors.lastname: DeGrado
authors.forename: P
authors.initials: P
authors.lastname: Chakraborty
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
authors.forename: M
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000493:pharmacokinetics; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000294:innervation; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002250:Carbon Radioisotopes; D012110:Reserpine; D003891:Desipramine; D004837:Epinephrine