MYOCARDIAL KINETICS OF CARBON-11-EPINEPHRINE IN THE ISOLATED WORKING RAT-HEART

The kinetics of EPI were studied in the isolated rat heart model to ev aluate C-11-epinephrine (EPI) as a radiotracer for the assessment of s ympathetic neuronal function in the heart. Methods: Isolated rat heart s were perfused in a working mode. Carbon-11-EPI was added to the perf usate 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 C-11 radioactivity as intact tracer. Results: Time-activity curves of cont rol hearts showed that C-11-EPI is taken up and retained by the myocar dium. Desipramine inhibition (DMI) of uptake-1 resulted in a significa nt decrease in myocardial uptake and retention of C-11-EPI by 91% comp ared to controls. Addition of DMI to the perfusion medium during washo ut did not affect kinetics of C-11-EPI compared to control hearts. Res erpine pretreated rat hearts also showed significant decrease in trace r retention of 95% compared to controls. The metabolic data showed tha t, in control conditions, about 61% of C-11-EPI taken up by the rat he art is rapidly metabolized and released. Conclusion: Carbon-11-EPI tra ces sympathetic nerve terminals in the isolated rat heart. Uptake bloc kade by DMI and reserpine suggest that uptake and storage of C-11-EPI appear to be similar to that of norepinephrine. However, the prominent metabolic pathway warrants further consideration. These results sugge st that C-11-EPI may be a suitable radiolabeled tracer for the evaluat ion of sympathetic vesicular function of the heart by PET.