Diabetes-Induced Changes in Cardiac Nerve Function
Marie Louise Muus Ghorbani
Patients with diabetes have an increased mortality rate compared to the non-diabetic population. They also have an increased risk of developing cardiovascular disease, with ischemic heart disease being the most frequently seen and the one accountable for most deaths among patients with diabetes. Autonomic neuropathy is believed to contribute to the high mortality in these patients but the impact by diabetes on sensory nerves in diabetic cardiovascular autonomic neuropathy is an overlooked area.
The purpose of this PhD project was to investigate diabetes-induced effects on the function of sensory neurons innervating the heart in two rodent models of diabetes.
An in vivo model was employed for studying spinal neuron activity in neurons from streptozotocin-induced diabetic (STZ) rats, a model for type 1 diabetes. The neuron activity was assessed by extracellular single-cell electrophysiological recordings of spinal neurons in the T3 thoracic spinal cord segment. The response was recorded following innocuous and noxious somatic stimulation and intrapericardial application of algogenic substances normally released during ischemia, at pH 7.4. The study showed complex activity changes in the neurons from diabetic animals, assessed by hyper- and hyposensitivity in the spinal neurons following chemical and somatic stimulation.
Changes in intracellular calcium, the basis of neuronal function, was studied in vitro in dorsal root ganglion (DRG) neurons (cervical C8 to thoracic T5 spinal level) from Zucker Diabetic Fatty (ZDF) rats, an animal model for type 2 diabetes. The calcium activity was investigated in neurons retrogradely labeled from the heart as well as in unlabeled neurons. K+-induced depolarization was investigated in the DRG neurons and capsaicin was furthermore used for stimulating the neurons, alone and in combination with the algogenic substances, employed in the in vivo study, at pH 7.4 and 6. Results showed that neurons isolated from ZDF-rats elicited a greater calcium response to both K+ and capsaicin. However, no statistical differences were found between the two animal groups when stimulating with the combination of capsaicin and algogenic substances.
Both STZ and ZDF diabetic animals had diabetes-induced altered nerve function and are suited for studies that investigate the impact of diabetes on sensory neuronal function.
This PhD project has shown that diabetes causes functional neuronal changes in several levels of the nociceptive process from the heart which could have an impact on pain perception during myocardial ischemia and infarction as well as on the autonomic cardiac reflexes.
