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.

Conclusion: 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.