Regional In Vivo and In Vitro Characterization of Autonomic Innervation in Cardiomyopathic Human Heart

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Abstract
Background —In contrast to healthy volunteers, regional differences of cardiac autonomic innervation have been described through the use of C 11 -hydroxyephedrine positron emission tomography (HED-PET) in the left ventricles of patients with dilated cardiomyopathy. The goal of the present study was to correlate HED-PET images with biochemical analysis of tissue samples. Methods and Results —To assess the significance of altered HED uptake, we used HED-PET to examine eight patients with dilated cardiomyopathy before heart transplantation. After explantation, we measured the density and affinity of uptake 1 ( 3 H-mazindol binding) and tissue norepinephrine content as markers of presynaptic function, and we determined β-receptor density and affinity ( 3 H-CGP 12177 binding) in the corresponding areas of the same patients. The density of uptake 1 and norepinephrine content showed marked regional variation, with highest values in the anterior septal wall and lowest in inferoapical and apical areas. Both parameters were closely correlated ( r =.65, P =.05). Similarly, uptake 1 density or norepinephrine content and HED retention (PET) showed clear correlations ( r =.63 and .60, respectively). Uptake 1 affinities did not vary significantly and were not correlated to the other parameters. β-Adrenergic receptor density showed some, albeit less pronounced, regional variation and was weakly correlated to uptake 1 density and local HED retention ( r =.38 and .31, respectively). Conclusions —Uptake 1 density and tissue norepinephrine content showed marked regional variation in cardiomyopathic left ventricles. HED-PET is significantly correlated to the density but not the affinity of uptake 1 sites in the human heart, suggesting either loss of neurons or downregulation of uptake 1 in dilated cardiomyopathy. HED-PET is a valuable marker for alterations of the presynaptic sympathoadrenergic system in humans.

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