Skip Navigation

European Heart Journal 2001 22(17):1594-1600; doi:10.1053/euhj.2000.2556
Copyright © 2001 by the European Society of Cardiology.
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (7)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bengel, F.M.
Right arrow Articles by Schwaiger, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bengel, F.M.
Right arrow Articles by Schwaiger, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart; a non-invasive study using positron emission tomography

F.M. Bengela,f1, B. Permanetterb, M. Ungererc, S.G. Nekollaa and M. Schwaigera

a Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Germany
b Abteilung Innere Medizin, Kreiskrankenhaus Fürstenfeldbruck, Germany
c I. Medizinische Klinik der Technischen Universität München, Germany

revised November 27, 2000; accepted November 28, 2000

Abstract

Aims To identify functional and metabolic correlates of impaired presynaptic sympathetic innervation in the cardiomyopathic human heart using non-invasive correlative imaging.

Methods and Results In 10 patients with idiopathic dilated cardiomyopathy, presynaptic catecholamine uptake sites were quantified by positron emission tomography with C-11 hydroxyephedrine. Oxidative metabolism was measured using C-11 acetate. Global and regional function was assessed by tomographic radionuclide angiography. Left ventricular ejection fraction in patients was 19%±10%. Myocardial hydroxyephedrine retention was abnormally low in 58%±38% of the left ventricles. Globally and regionally, hydroxyephedrine retention was significantly correlated with ventricular function (r=0·67, P=0·03 with left ventricular ejection fraction; r=0·31, P<0·01 with regional endocardial shortening). Multivariate analysis confirmed hydroxyephedrine retention as the closest independent determinant of left ventricular ejection fraction. Oxidative metabolism was determined by rate pressure product as a measure of workload (r=0·78, P<0·01) and peripheral vascular resistance as a measure of afterload (r=–0·61, P=0·06), but did not correlate with hydroxyephedrine retention (r=0·08 for global, r=0·04 for regional parameters).

Conclusion Alterations of presynaptic sympathetic innervation in dilated cardiomyopathy are associated with impaired contractile function, suggesting a common pathogenetic pathway. Overall oxidative metabolism, however, was not directly correlated with these findings. Normal regulatory mechanisms for oxidative metabolism were operational.

Key Words: Positron emission tomography, autonomic nervous system, oxidative metabolism, heart failure, left ventricular function

f1 Correspondence: Frank M. Bengel, MD, Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 München, Germany.

References

  1. Eisenhofer G, Friberg P, Rundqvist B. Cardiac sympathetic nerve function in congestive heart failure. Circulation. 1996;93:1667–1676[Abstract/Free Full Text]
  2. Beau SL, Saffitz JE. Transmural heterogeneity of norepinephrine uptake in failing human hearts. J Am Coll Cardiol. 1994;23:579–585[Abstract]
  3. Liang CS, Fan THM, Sullebarger JT, Sakamoto S. Decreased adrenergic neuronal uptake activity in experimental right heart failure. J Clin Invest. 1989;84:1267–1275[Web of Science][Medline]
  4. Ungerer M, Hartmann F, Karoglan M. Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart. Circulation. 1998;97:174–180[Abstract/Free Full Text]
  5. Böhm M, La Rosee K, Schwinger RHG, Erdmann E. Evidence for reduction of norepinephrine uptake sites in the failing human heart. J Am Coll Cardiol. 1995;25:146–153[Abstract]
  6. Henderson EB, Kahn JK, Corbett JR. Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy. Circulation. 1988;78:1192–1199[Abstract/Free Full Text]
  7. Feldman AM, Cates AE, Bristow ME, VanDop C. Altered expression of the a-subunits of G-proteins in failing human hearts. J Mol Cell Cardiol. 1989;21:359–365[CrossRef][Web of Science][Medline]
  8. Böhm M, Reiger B, Schwinger RH, Erdmann E. cAMP concentrations, cAMP dependent protein kinase activity, and phospholamban in non-failing and failing myocardium. Cardiovasc Res. 1994;28:1713–1719[Web of Science][Medline]
  9. Mann DL, Kent RL, Parsons B, Cooper G. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation. 1992;85:790–804[Abstract/Free Full Text]
  10. Opie LH, Thandroyen FT, Muller CA, Bricknell OL. Adrenaline-induced ‘oxygen-wastage’ and enzyme release from working rat heart. Effects of calcium antagonism, beta-blockade, nicotinic acid and coronary artery ligation. J Mol Cell Cardiol. 1979;11:1073–1094[CrossRef][Web of Science][Medline]
  11. Hartmann F, Ziegler S, Nekolla S. Regional patterns of myocardial sympathetic denervation in dilated cardiomyopathy: an analysis using carbon-11 hydroxyephedrine (HED) and positron emission tomography. Heart. 1999;81:262–270[Abstract/Free Full Text]
  12. Merlet P, Valette H, Dubois RJ. Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med. 1992;33:471–477[Abstract/Free Full Text]
  13. Merlet P, Benvenuti C, Moyse D. Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy. J Nucl Med. 1999;40:917–923[Abstract/Free Full Text]
  14. Pike VW, Eakins MN, Allan RM, Selwyn AP. Preparation of (1-11C) acetate—an agent for the study of myocardial metabolism by positron emission tomography. Int J Appl Radiat Isot. 1982;33:505–512[CrossRef][Medline]
  15. Rosenspire KC, Haka MS, Van DM. Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging. J Nucl Med. 1990;31:1328–1334[Abstract/Free Full Text]
  16. Nekolla SG, Stollfuß J, Bachmann R, Spyra L, Neverve J, Schwaiger M. Automated assessment of LV-EF and volumes by gated bloodpool SPECT: comparison to gated MRI (abstract). J Nucl Med. 1996;37:218P
  17. Nekolla SG, Miethaner C, Nguyen N, Ziegler SI, Schwaiger M. Reproducibility of polar map generation and assessment of defect severity and extent assessment in myocardial perfusion imaging using positron emission tomography. Eur J Nucl Med. 1998;25:1313–1321[CrossRef][Web of Science][Medline]
  18. Gropler RJ, Siegel BA, Geltman EM. Myocardial uptake of carbon-11-acetate as an indirect estimate of regional myocardial blood flow. J Nucl Med. 1991;32:245–251[Abstract/Free Full Text]
  19. Buxton DB, Schwaiger M, Nguyen A, Phelps ME, Schelbert HR. Radiolabelled acetate as a tracer of myocardial tricarboxylic acid cycle flux. Circ Res. 1988;63:628–634[Abstract/Free Full Text]
  20. Armbrecht JJ, Buxton DB, Schelbert HR. Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium. Circulation. 1990;81:1594–1605[Abstract/Free Full Text]
  21. Schwaiger M, Kalff V, Rosenspire K. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation. 1990;82:457–464[Abstract/Free Full Text]
  22. Vesalainen RK, Pietila M, Tahvanainen KU. Cardiac positron emission tomography imaging with C-11 hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure. Am J Cardiol. 1999;84:568–574[CrossRef][Web of Science][Medline]
  23. Bristow MR. The autonomic nervous system in heart failure. N Engl J Med. 1984;311:850–851[Web of Science][Medline]
  24. Hajjar RJ, Müller FU, Schmitz W, Schnabel P, Böhm M. Molecular aspects of adrenergic signal transduction in cardiac failure. J Mol Med. 1998;76:747–755[CrossRef][Web of Science][Medline]
  25. Katz AM. Changing strategies in the management of heart failure. J Am Coll Cardiol. 1989;13:513–523[Abstract]
  26. Neubauer S, Krahe T, Schindler R. 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Circulation. 1992;86:1810–1818[Abstract/Free Full Text]
  27. Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation. 1996;94:2837–2842[Abstract/Free Full Text]
  28. Gunning JF, Coleman HN. Myocardial oxygen consumption during experimental hypertrophy and congestive heart failure. J Mol Cell Cardiol. 1973;5:25–38[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
T. Sasano, M. R. Abraham, K.-C. Chang, H. Ashikaga, K. J. Mills, D. P. Holt, J. Hilton, S. G. Nekolla, J. Dong, A. C. Lardo, et al.
Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction.
J. Am. Coll. Cardiol., June 10, 2008; 51(23): 2266 - 2275.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
A. L'Abbate and G. Sambuceti
Studying the neuronal side of the synaptic cleft. A tool for investigating the paradox of sympathetic nervous system and heart failure in dilated cardiomyopathy
Eur. Heart J., September 1, 2001; 22(17): 1521 - 1522.
[PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (7)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bengel, F.M.
Right arrow Articles by Schwaiger, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bengel, F.M.
Right arrow Articles by Schwaiger, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?