Abstract
BackgroundAlthough cardiac autonomic neuropathy is one of major complications of diabetes mellitus (DM), anatomical data on cardiac innervation of diabetic animal models is scant and controversial. We performed this study to check whether long-term diabetic state impacts the anatomy of intracardiac ganglia in Goto-Kakizaki (GK) rats, a genetic model of type 2 DM.MethodsTwelve GK rats (276 ± 17 days of age; mean ± standard error) and 13 metabolically healthy Wistar rats (262 ± 5 days of age) as controls were used for this study. Blood glucose was determined using test strips, plasma insulin by radioimmunoassay. Intrinsic ganglia and nerves were visualized by acetylcholinesterase histochemistry on whole hearts. Ganglion area was measured, and the neuronal number was assessed according to ganglion area.ResultsThe GK rats had significantly elevated blood glucose level compared to controls (11.0 ± 0.6 vs. 5.9 ± 0.1 mmol/l, p < 0.001), but concentration of plasma insulin did not differ significantly between the two groups (84.0 ± 9.8 vs. 67.4 ± 10.9 pmol/l, p = 0.17). The GK rats contained significantly fewer intracardiac ganglia, decreased total area of intracardiac ganglia (1.4 ± 0.1 vs. 2.2 ± 0.1 mm2, p < 0.001) and smaller somata of ganglionic neurons. Mean total number of intracardiac neurons in GK rats was 1461 ± 62, while this number in control rats was higher by 39% and reached 2395 ± 110 (p < 0.001).ConclusionsResults of our study demonstrate the decreased number of intracardiac neurons in GK rats compared to metabolically healthy Wistar rats of similar age. It is likely that the observed structural remodelling of intracardiac ganglia in GK rats is caused by a long-term diabetic state.
Highlights
Cardiac autonomic neuropathy is one of major complications of diabetes mellitus (DM), anatomical data on cardiac innervation of diabetic animal models is scant and controversial
The mechanisms of cardiac autonomic neuropathy in DM are poorly understood, functional studies imply the role of intracardiac ganglia in development of baroreflex circuitry defects and arrhythmias [16,17]
Total number and size of intracardiac neurons Strong correlation between the ganglion area and neuronal number was found both for GK rats and controls (Figure 3a, b)
Summary
Cardiac autonomic neuropathy is one of major complications of diabetes mellitus (DM), anatomical data on cardiac innervation of diabetic animal models is scant and controversial. Long-term diabetes mellitus (DM) impacts the ultrastructure, cytochemistry and function of neurons and nerves, and leads to a variety of neuropathies [1,2,3,4]. The mechanisms of cardiac autonomic neuropathy in DM are poorly understood, functional studies imply the role of intracardiac ganglia in development of baroreflex circuitry defects and arrhythmias [16,17]. Degenerative ultrastructural changes of the nerve fibres have been demonstrated within atria of diabetic patients [1] and animal models [9]. Other authors found unchanged abundance of cholinergic neurons and even increased density of the cholinergic nerve fibres in the region of sinoatrial node of diabetic mice [18]
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