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Myocardial Kinetics of Carbon-11-Epinephrine in the Isolated Working Rat Heart

Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

Correspondence: For correspondence or reprints contact: Ngoc Nguyen, Department of Nuclear Medicine, Klinikum rechts der lear, Ismaningerstr. 22, 81675 Munich, Germany.

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-i 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 signfficant 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.

Key Words: carbon-11-epinephrine • cardiac sympathetic innervation • PET

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