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Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects

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Abstract

The purpose of this study was to determine the effect of the oral administration of pyridostigmine bromide on indices of heart rate variability (HRV) in healthy young volunteers. Seventeen healthy participants (11 men, 6 women; aged 27±8 y) submitted to a randomized, crossover, double-blind protocol, in which they received 30 mg pyridostigmine bromide (PYR) or placebo orally at 8-hour intervals for 24 hours, on two separate days. Venous blood samples were collected 2 and 24 hours after the first dose for determination of serum cholinesterase activity. Holter tapes were recorded during the 24-hour period and analyzed using a semiautomatic technique to evaluate time- and frequency-domain indices of HRV and to build three-dimensional return maps for later quantification. Symptoms were mild and occurred similarly during administration of PYR and placebo (p=0.140). Serum cholinesterase activity was reduced by 15% at 2 hours (p=0.013) and by 14% at 24 hours (p=0.010) after the first dose of PYR, but not after administration of placebo. Pyridostigmine administration caused a significant increase in the mean 24-hour R-R interval (placebo: 814±20 msec; PYR: 844±18 msec; p=0.003) and in time-domain indices of HRV, such as the standard deviation of all R-R intervals (SDNN; placebo: 151±9 msec; PYR: 164 ±9 msec; p=0.017), and the percentage of pairs of adjacent R-R intervals differing by more than 50 msec (pNN50; placebo: 12.8±1.8%; PYR: 13.9±1.5%; p=0.029). Pyridostigmine had no significant effect on frequency-domain indices of HRV, but resulted in significant increase in P2, a parasympathetic index derived from the three-dimensional return map (placebo: 93±13 msec; PYR: 98±13 ms; p=0.029). In conclusion, low-dose pyridostigmine reduced mean heart rate and increased HRV during a 24-hour period in healthy young subjects.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Universidade Federal Fluminense, Rua Prof. Hernani Melo 101, Centro, Niterói, 24220-111, Rio de Janeiro, Brazil

    Antonio Claudio L. Nóbrega M.D., Sc.D. & Bianca Gouvêa Bastos M.D.

  2. Post-Graduate Program in Cardiology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil

    Antonio Claudio L. Nóbrega M.D., Sc.D. & Amália Faria dos Reis M.D., M.Sc.

  3. Cardiology Division, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Ruy S. Moraes M.D., Sc.D. & Jorge P. Ribeiro M.D., Sc.D.

  4. Biomedical Engineering, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

    Elton L. Ferlin B.Sc.EE

  5. Department of Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Jorge P. Ribeiro M.D., Sc.D.

Authors
  1. Antonio Claudio L. Nóbrega M.D., Sc.D.
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  2. Amália Faria dos Reis M.D., M.Sc.
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  3. Ruy S. Moraes M.D., Sc.D.
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  4. Bianca Gouvêa Bastos M.D.
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  5. Elton L. Ferlin B.Sc.EE
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  6. Jorge P. Ribeiro M.D., Sc.D.
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Correspondence to Antonio Claudio L. Nóbrega M.D., Sc.D..

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Supported by the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasilia, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasilia, and Programa de Incentivo de Núcleos de Excelência (PRONEX), Brasilia.

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Nóbrega, A.C.L., dos Reis, A.F., Moraes, R.S. et al. Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects. Clinical Autonomic Research 11, 11–17 (2001). https://doi.org/10.1007/BF02317797

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