Figure 1.

Concept diagrams for the effects of cardiac sympathetic denervation with or without decreased vesicular storage on myocardial radioactivity after administration of ¹⁸F‐dopamine (¹⁸F‐DA) or ¹¹C‐methylreboxetine (¹¹C‐MRB). (A) When there is intact innervation (NORMAL), ¹⁸F‐DA is taken up into sympathetic nerves via the cell membrane norepinephrine transporter (NET). Cytoplasmic ¹⁸F‐DA is then mainly taken up into vesicles via the vesicular monoamine transporter (VMAT), with a minor alternative fate oxidative deamination to form ¹⁸F‐dihydroxyphenylacetic acid (¹⁸F‐DOPAC), which rapidly exits the neurons. ¹¹C‐MRB binds to the NET but does not enter the neurons. Myocardial ¹¹C‐MRB‐derived radioactivity reflects high‐affinity NET binding. (B) Denervation (DENERVATION) equivalently decreases ¹⁸F‐DA‐ and ¹¹C‐MRB‐derived radioactivity (equally small green and red circles). The objects in (B) and (C) are smaller than those in (A), to convey the loss of sympathetic neurons. (C) Combined denervation with decreased vesicular storage (DENERVATION + DEC. VESIC. STORAGE) reduces ¹⁸F‐DA‐derived radioactivity more than ¹¹C‐MRB‐derived radioactivity. (D) Effects of denervation on ¹⁸F‐DA‐derived radioactivity as a function of time. The gray rectangles show the 3‐minute period of intravenous infusion of the tracer. Denervation shifts downward the curve relating the log of ¹⁸F‐DA‐derived radioactivity vs. time (from gray line to blue line), without a change in slope. (E) Combined denervation and decreased vesicular storage decreases peak radioactivity and accelerates the loss of radioactivity (purple line).