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Cited by 224Heart Rate Variability and Autonomic ControlCardiac electrophysiology and arrhythmiasCardiovascular Function and Risk Factors

Cardiac Sympathetic Dysinnervation in Diabetes: Implications for Enhanced Cardiovascular Risk

Stevens, Martin J., Raffel, David M., Allman, Kevin C., Dayanikli, Firat, Ficaro, Edward, Sandford, Tracy, Wieland, Donald M., Pfeifer, Michael A. +1 more·1998·Circulation
DOI 10.1161/01.cir.98.10.961
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Abstract

Background —Regional cardiac sympathetic hyperactivity predisposes to malignant arrhythmias in nondiabetic cardiac disease. Conversely, however, cardiac sympathetic denervation predicts increased morbidity and mortality in severe diabetic autonomic neuropathy (DAN). To unite these divergent observations, we propose that in diabetes regional cardiac denervation may elsewhere induce regional sympathetic hyperactivity, which may in turn act as a focus for chemical and electrical instability. Therefore, the aim of this study was to explore regional changes in sympathetic neuronal density and tone in diabetic patients with and without DAN. Methods and Results —PET using the sympathetic neurotransmitter analogue 11 C-labeled hydroxyephedrine ([ 11 C]-HED) was used to characterize left ventricular sympathetic innervation in diabetic patients by assessing regional disturbances in myocardial tracer retention and washout. The subject groups comprised 10 diabetic subjects without DAN, 10 diabetic subjects with mild DAN, 9 diabetic subjects with severe DAN, and 10 healthy subjects. Abnormalities of cardiac [ 11 C]-HED retention were detected in 40% of DAN-free diabetic subjects. In subjects with mild neuropathy, tracer defects were observed only in the distal inferior wall of the left ventricle, whereas with more severe neuropathy, defects extended to involve the distal and proximal anterolateral and inferior walls. Absolute [ 11 C]-HED retention was found to be increased by 33% ( P <0.01) in the proximal segments of the severe DAN subjects compared with the same regions in the DAN-free subjects (30%; P <0.01 greater than the proximal segments of the mild DAN subjects). Despite the increased tracer retention, no appreciable washout of tracer was observed in the proximal segments, consistent with normal regional tone but increased sympathetic innervation. Distally, [ 11 C]-HED retention was decreased in severe DAN by 33% ( P <0.01) compared with the DAN-free diabetic subjects (21%; P <0.05 lower than the distal segments of the mild DAN subjects). Conclusions —Diabetes may result in left ventricular sympathetic dysinnervation with proximal hyperinnervation complicating distal denervation. This combination could result in potentially life-threatening myocardial electrical instability and explain the enhanced cardioprotection from β-blockade in these subjects.

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Authors
Stevens, M. J., Raffel, D. M., Allman, K. C., Dayanikli, F., Ficaro, E., Sandford, T., Wieland, D. M., Pfeifer, M. A., & Schwaiger, M.
Affiliations
SIU Medicine (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1998-09-08
Volume
98
Issue
10
Pages
961-968
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.98.10.961
OpenAlex
W2124098112
Cited by
224
References
49
Citations by year
2026: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 5 · 2018: 1 · 2017: 8 · 2016: 4 · 2015: 7 · 2014: 11 · 2013: 15 · 2012: 14
FWCI
5.68
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Michigan
  • National Institutes of Health (1r01hl047543-01)
  • National Heart, Lung, and Blood Institute (R01-HL-47543)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
diabetic autonomic neuropathy, diabetes mellitus, cardiac sympathetic innervation, left ventricular wall, myocardial electrical instability, malignant arrhythmias
MeSH terms
Adult, Analysis of Variance, Carbon Radioisotopes, Denervation, Diabetic Neuropathies, Ephedrine, Female, Heart, Heart Rate, Heart Ventricles, Humans, Image Processing, Computer-Assisted, Male, Neurons, Reference Values, Sympathetic Nervous System, Tomography, Emission-Computed, Ventricular Dysfunction, Left

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