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(Circulation. 1998;97:174-180.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

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

Martin Ungerer, MD; Franz Hartmann, MD; Mislav Karoglan, MS; Andreas Chlistalla, MS; Sibylle Ziegler, PhD; Gert Richardt, MD; Matthias Overbeck, MD; Hans Meisner, MD; Albert Schömig, MD; ; Markus Schwaiger, MD

From 1. Medizinische Klinik (M.U., F.H., M.K., A.C., G.R., A.S.) and Herzchirurgie (M.O., H.M.), Deutsches Herzzentrum, and Nuklearmedizinische Klinik (S.Z., M.S.), Technische Universität München, Munich, Germany.

Correspondence to Dr Martin Ungerer, 1. Medizinische Klinik der Technischen, Universität München, Klinikum rechts der Isar, Ismaningerstr 22, 81675 München, Germany. E-mail ungerer{at}med1.med.tu-muenchen.de

Background—In contrast to healthy volunteers, regional differences of cardiac autonomic innervation have been described through the use of C¹¹-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 uptake₁ (³H-mazindol binding) and tissue norepinephrine content as markers of presynaptic function, and we determined ß-receptor density and affinity (³H-CGP 12177 binding) in the corresponding areas of the same patients. The density of uptake₁ 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, uptake₁ density or norepinephrine content and HED retention (PET) showed clear correlations (r=.63 and .60, respectively). Uptake₁ affinities did not vary significantly and were not correlated to the other parameters. ß-Adrenergic receptor density showed some, albeit less pronounced, regional variation and was weakly correlated to uptake₁ density and local HED retention (r=.38 and .31, respectively).

Conclusions—Uptake₁ 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 uptake₁ sites in the human heart, suggesting either loss of neurons or downregulation of uptake₁ in dilated cardiomyopathy. HED-PET is a valuable marker for alterations of the presynaptic sympathoadrenergic system in humans.

Key Words: heart failure • cardiomyopathy • tomography • nervous system, autonomic

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