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The initial level of heart rate variability determines the dynamics of the neuropathy of the autonomic nervous system and temperature sensitivity in rats with streptozotocin diabetes

https://doi.org/10.14341/DM10069

Abstract

BACKGROUND: The development of diabetes mellitus (DM) is accompanied by hyperglycemia, which leads to the development of neuropathy. We assume that the individual characteristics of the organization of the autonomic nervous system (ANS) in humans affect not only the ability to withstand stress, but can determine the course of diseases, including diabetes.


AIMS: The study of the dynamics of heart rate variability and temperature sensitivity in rats against the background of hyperglycemia depending on the organization of the initial regulation of the heart under ANS.


MATERIALS AND METHODS: 70 male rats were randomized by weight and level of total heart rate variability (HRV) on animals with initially low and high levels of total HRV. Diabetes was modeled by a single i.p. injection of streptozotocin (STZ). The control group received a single i.p. injection of citrate buffer (CB). Before the induction of diabetes, as well as on 21, 42 and 70 days after the injection of STZ, a comprehensive examination of rats’ condition was carried out: 1) assessment of HRV; 2) analysis of temperature-pain sensitivity; 3) assessment of glucose and ketone bodies in the blood. Similarly, animals in the CB group were examined.


RESULTS: The change in HRV and temperature-pain sensitivity in rats depends on the initial level of HRV. In rats with low variability, the reaction time in the pain test increased by 8–32% from the 28th day of the experiment, from 21 days the bradycardia increased and the decrease in individual HRV indices at rest, but not the response of these parameters to cold stress.


CONCLUSION: The development of ANS’s lesion depends on the initial level of HRV. Low variability animals are more resistant to hyperglycemia: the normal ranges of CP reactions from the side of HR, the parameters of total HRV and the CVHS contribution to it are longer, but there is a loss of temperature sensitivity. Initially, highly variable rats with the development of diabetes do not lose temperature sensitivity, but demonstrate an imbalance in the regulatory circuits of heart rate and HRV.

About the Authors

Maria P. Morozova

M.V. Lomonosov Moscow State University


Russian Federation

PhD in Biology, assistant



Svetlana A. Gavrilova

M.V. Lomonosov Moscow State University


Russian Federation

PhD in Biology, Associate Professor



Evgeniy V. Ivanov

M.V. Lomonosov Moscow State University


Russian Federation

PhD Student



Aleksei K. Erdiakov

M.V. Lomonosov Moscow State University


Russian Federation

PhD in Biology, Senior Researcher



Ekaterina M. Rzhavina

M.V. Lomonosov Moscow State University


Russian Federation

PhD Student



Vladimir B. Koshelev

M.V. Lomonosov Moscow State University


Russian Federation

PhD, D.Sc., Professor



Gagik R. Galstyan

Endocrinology Research Centre


Russian Federation

MD, PhD, D. Sc., Professor



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Supplementary files

1. Fig. 1. Dynamics of temperature sensitivity (tail twitching time) in rats with streptozotocin-induced diabetes mellitus. * - p <0.05, ** - p <0.01 - statistically significant differences between the HB-CB and HB-CD groups; # - p <0.05, statistically significant differences between the BB-CB and BB-SD groups.
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2. Fig. 2. Dynamics of heart rate in rats after modeling streptozotocin diabetes. @ - p <0.00001 - statistically significant differences from the 0th day of their group; $ - p <0.05 - statistically significant differences between the groups of HB-SD and BB-SD.
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3. Fig. 3. The dynamics of the reaction of heart rate in rats immediately after a cold test. ** - p <0.001; *** - p <0.0001; **** - p <0.00001 - statistically significant differences from the level of rest; @ - p <0.05 - statistically significant differences within the highly variable group on the 70th day from the 0th and 21st days of the experiment.
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4. Fig. 4. Change in the total heart rate variability, SDRR, in response to a cold test in rats with diabetes mellitus development: * - p <0.05; ** - p <0.001; **** - p <0.00001 - statistically significant differences from the level of rest; $ - p <0.05, $$$ - p <0.001 - statistically significant differences between HB and BB rats within the same time point; @ - p <0.05; @@ - p <0.01; @@@ - p <0.001– statistically significant differences within the group of highly variable rats at different stages of diabetes mellitus.
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5. Fig. 5. Dynamics of the response of pNN3 to a cold test in rats with initially different heart rate variability against the background of the development of diabetes mellitus: * - p <0.05; ** - p <0.001; **** - p <0.00001 - statistically significant differences in the response amplitude from the resting level; @ - p <0.05 - statistically significant differences within the group of highly variable rats at different stages of diabetes. The dashed line shows the comparison points within the same group (BB) at different stages of diabetes
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6. Fig. 6. Dynamics of the response of the SDARR indicator to a cold test in rats with initially different heart rate variability against the background of the development of diabetes mellitus: * - p <0.05; ** - p <0.001; **** - p <0.00001 - statistically significant differences from the level of rest; $ - p <0.05 - statistically significant differences between low-variable and high-variable rats within the same time point; @ - p <0.05 - statistically significant differences within the group of highly variable rats at different stages of diabetes
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Review

For citations:


Morozova M.P., Gavrilova S.A., Ivanov E.V., Erdiakov A.K., Rzhavina E.M., Koshelev V.B., Galstyan G.R. The initial level of heart rate variability determines the dynamics of the neuropathy of the autonomic nervous system and temperature sensitivity in rats with streptozotocin diabetes. Diabetes mellitus. 2019;22(3):233-243. (In Russ.) https://doi.org/10.14341/DM10069

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ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)