Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

Serra, Salvador Manoel; Costa, Ricardo; Bastos, Bianca Gouvêa; Santos, Kelb Bousquet; Ramalho, Sérgio Henrique Rodolpho; Nóbrega, Antônio Cláudio Lucas da

doi:10.1590/s0066-782x2001000400002

Cited by 9 publications

(4 citation statements)

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“…6 The systematic study of its haemodynamic effects has shown that pyridostigmine decreases resting 7 15 and exercise heart rate 10 and reduces QTc dispersion 15 in healthy people without impairing exercise tolerance. 10 When administered at eight hour intervals, pyridostigmine elicited sustained 24 hour bradycardia and augmented heart rate variability. 8 All of these effects were obtained without impairment of systolic or diastolic cardiac functions.…”

Section: Discussionmentioning

confidence: 99%

“…In healthy volunteers, pyridostigmine decreased resting heart rate, 7 increased heart rate variability, 8 and blunted the cardiac response to mental stress 9 and to dynamic exercise. 10 In the clinical setting, pyridostigmine has been shown to increase heart rate variability and to decrease the density of ventricular arrhythmia 11 in patients with heart failure. However, the effects of pyridostigmine in patients with coronary artery disease are largely unknown.…”

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confidence: 99%

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Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia

Castro

Porphirio²,

Serra³

et al. 2004

Heart

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Objective: To determine the acute effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, during exercise in patients with coronary artery disease. Design: Double blind, randomised, placebo controlled, crossover study. Setting: Outpatients evaluated in an exercise test laboratory. Patients: 15 patients with exercise induced myocardial ischaemia. Interventions: Maximal cardiopulmonary exercise test on a treadmill according to an individualised ramp protocol on three days. The first day was used for adaptation to the equipment and to determine exercise tolerance and the presence of exercise induced ischaemia. On the other two days, the cardiopulmonary exercise test was performed two hours after oral administration of pyridostigmine (45 mg) or placebo. All patients were taking their usual medication during the experiments. Main outcome measures: Rate-pressure product and oxygen uptake during exercise. Results: Pyridostigmine inhibited the submaximum chronotropic response (p = 0.001), delaying the onset of myocardial ischaemia, which occurred at a similar rate-pressure product (mean (SE) placebo 20.55 (1.08) mm Hg 6 beats/min 10 3 ; pyridostigmine 19.75 (1.28) mm Hg 6 beats/min 10 3 ; p = 0.27) but at a higher exercise intensity (oxygen consumption: placebo 18.6 (1.7) ml/kg/min; pyridostigmine 19.6 (1.8) ml/kg/min; p = 0.03). Also, pyridostigmine increased peak oxygen consumption (placebo 23.6 (2) ml/kg/min; pyridostigmine 24.8 (2) ml/kg/min; p = 0.01) and peak oxygen pulse (placebo 12.9 (1) ml/beat; pyridostigmine 13.6 (1) ml/beat; p = 0.02). Conclusions: Pyridostigmine improved peak exercise tolerance and inhibited the chronotropic response to submaximum exercise, increasing the intensity at which myocardial ischaemia occurred. These results suggest that pyridostigmine can protect against exercise induced myocardial ischaemia.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia

Castro

Porphirio²,

Serra³

et al. 2004

Heart

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“…Anticholinesterase inhibitors act directly on cardiac ganglion cells producing acetylcholine release and activation of cardiac M 2 receptors [51,52]. In addition, PYR blunts the rate-pressure product increase during men-tal stress [33] and inhibits the chronotropic response to dynamic exercise without reducing functional capacity [32]. In addition, PYR blunts the rate-pressure product increase during men-tal stress [33] and inhibits the chronotropic response to dynamic exercise without reducing functional capacity [32].…”

Section: Pyridostigmine Bromidementioning

confidence: 99%

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

et al. 2001

Clinical Autonomic Research

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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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“…When used in health adults pyridostigmine reduces rest QTc dispersion 9 and lowers heart rate during rest and exercise without hypotension. 9,10 In patients with coronary artery disease pyridostigmine reduces QTc interval 11 and delays the onset of exercise-induced myocardial ischemia, inhibiting chronotropic response to exercise and improving peak exercise tolerance. 12 It also reduces QTc interval during recovery from maximal exercise in ischemic heart disease.…”

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confidence: 99%

Cholinergic stimulation may mitigate arrhythmic risk during treatment of COVID-19

Castro¹,

Neves²,

Neto³

et al. 2020

IPMRJ

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Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

Abstract: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and during exercise, with minimal side effects and without interfering with exercise tolerance and ventilation variables.

Cited by 9 publications

References 35 publications

Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia

Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia

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

Cholinergic stimulation may mitigate arrhythmic risk during treatment of COVID-19

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