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Open Access Original investigation

The co-occurrence of myocardial dysfunction and peripheral insensate neuropathy in a streptozotocin-induced rat model of diabetes

Maria N Marangoni1, Scott T Brady1, Shamim A Chowdhury2 and Mariann R Piano3*

Author Affiliations

1 Department of Anatomy and Cell Biology, University of Illinois at Chicago, 808 S. Wood St. Rm 578 (M/C 512), Chicago, IL 60612, USA

2 Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott Ave (M/C 901), Chicago, IL 60612, USA

3 Department of Biobehavioral Health Science, University of Illinois at Chicago, 845 South Damen Avenue, Room 706 (M/C 802), Chicago, IL 60612-7350, USA

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Cardiovascular Diabetology 2014, 13:11  doi:10.1186/1475-2840-13-11

Published: 11 January 2014

Abstract

Background

Cardiomyopathy and distal symmetrical polyneuropathy (DSPN), including sensory and autonomic dysfunction, often co-occur in diabetic mellitus (DM) patients. However, the temporal relationship and progression between these two complications has not been investigated. Using a streptozotocin DM animal model that develops insensate neuropathy, our aim was to examine in parallel the development of DSPN and DM-associated changes in cardiac structure and function as well as potential mechanisms, such as autonomic dysfunction, evaluated by changes in urinary and myocardial norepinephrine content and myocardial neuronal markers.

Methods

Sensory neuropathy was measured by behavioral tests using Von Frey filaments and Hargreaves methods. Echocardiography was used to evaluate myocardial structure and function. Autonomic function was evaluated by measuring urinary and myocardial norepinephrine (NE) levels by enzyme-linked immunosorbent assay and high-performance liquid chromatography/mass spectrometry. Quantitative immunohistochemistry was used to measure the myocardial neuronal markers, calcitonin gene-related peptide (CGRP) and general neuronal protein gene product 9.5 (PGP 9.5).

Results

The DM group developed tactile and thermal insensate neuropathy 4–5 weeks after DM onset. Cardiovascular changes were found between 4 and 12 weeks after DM onset and included bradycardia, diastolic and systolic dysfunction and cardiac dilation. There was a 2.5-fold reduction in myocardial NE levels and a 5-fold increase in urinary NE levels in the DM group. Finally, there was a 2.3-fold increase in myocardial CGRP levels in the DM group and no change in PGP9.5 levels.

Conclusions

Cardiovascular structural and functional changes developed early in the course of DM and in combination with insensate neuropathy. In parallel, signs of cardiac autonomic dysfunction were also found and included decreased myocardial NE levels and altered CGRP levels. These results may indicate the need for early cardiovascular evaluation in DM patients with insensate neuropathy.

Keywords:
Insensate neuropathy; Systolic dysfunction; Diastolic dysfunction; Norepinephrine; Diabetic cardiomyopathy