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Comparative Analysis of Disorders of Heart Rhythm Regulation Mechanisms Induced in Newborn Rats by Nickel Chloride and the Acetylcholinesterase Inhibitor Physostigmine (Eserine)

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Abstract

A comparative analysis of heart rate variability (HRV) indices after injection of the acetylcholinesterase inhibitor (AChE) physostigmine (3/4 LD50) and the T-type calcium channel blocker (T-VDCC) Ni2+ (ED100) into animals was performed in experiments on 3-day-old newborn rats. Both drugs cause phenomenologically similar pathological heart rhythm with significant bradycardia complexes (PHRBC). Analysis of HRV indices showed that the disturbance of heart rhythm regulation mechanisms in NiCl2 poisoning of rats and in cholinoreactive structure activation caused by AChE inhibition develop according to a similar pattern. In both cases there is a decrease in the total power of the spectrum and the absolute power values of the LF (predominantly sympathetic) and HF (parasympathetic influences) bands. Significant decrease in the level of nerve influences leads to the fact that the dominant role in the regulation of heart rhythm begins to play neurohumoral factors (VLF-band). It was found that under conditions of premedication with N- or M-cholinolytics, when rats do not develop cardiac rhythm disturbances, the initial decrease in the severity of neurohumoral and subsequent increase in sympathetic and, to a lesser extent, parasympathetic influences is common. In this case, vagosympathetic balance is not decisive. In case the influence of neurohumoral factors increases after premedication, then later there is a decrease in the proportion of nerve influences and the occurrence of PHRBC. The obtained data suggest that in newborn rats both direct blockade of T-VDCC and changes in I CaT current mediated through M3-subtype muscarinic cholinoreceptors lead to disruption of pacing and development of PHRBC.

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Funding

The work was performed within the framework of state assignment No. 075-00967-23-00.

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Contributions

S.V.K. carried out planning, data collection and processing, and writing the article. N.N.K. carried out the preparation and conduct of experiments, as well as data processing.

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Correspondence to S. V. Kuznetsov.

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COMPLIANCE WITH ETHICAL STANDARDS

All applicable international, national and/or institutional principles of animal care and use were observed. All procedures performed in studies involving animals complied with the ethical standards approved by the legal acts of the Russian Federation, the principles of the Basel Declaration, and the recommendations of the Bioethics Committee of the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (Protocol no. 7-2/2020), based on the European Parliament Directive 2010/63/EU “On the Protection of Animals Used for Experimental Purposes”.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Additional information

Translated by A. Dyomina

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 8, pp. 1124–1139https://doi.org/10.31857/S0869813923080058.

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Kuznetsov, S.V., Kuznetsova, N.N. Comparative Analysis of Disorders of Heart Rhythm Regulation Mechanisms Induced in Newborn Rats by Nickel Chloride and the Acetylcholinesterase Inhibitor Physostigmine (Eserine). J Evol Biochem Phys 59, 1438–1451 (2023). https://doi.org/10.1134/S1234567823040341

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