Dewland TA, Androne AS, Lee FA, Lampert RJ, Katz SD. Effect of acetylcholinesterase inhibition with pyridostigmine on cardiac parasympathetic function in sedentary adults and trained athletes. Am J Physiol Heart Circ Physiol 293: H86-H92, 2007. First published February 23, 2007 doi:10.1152/ajpheart.01339.2006.-Heart rate variability and postexercise heart rate recovery are used to assess cardiac parasympathetic tone in human studies, but in some cases these indexes appear to yield discordant information. We utilized pyridostigmine, an acetylcholinesterase inhibitor that selectively augments the parasympathetic efferent signal, to further characterize parasympathetic regulation of rest and postexercise heart rate. We measured time-and frequency-domain indexes of resting heart rate variability and postexercise heart rate recovery in 10 sedentary adults and 10 aerobically trained athletes after a single oral dose of pyridostigmine (30 mg) and matching placebo in randomized, doubleblind, crossover trial. In sedentary adults, pyridostigmine decreased resting heart rate [from 66.7 (SD 12.6) to 58.1 beats/min (SD 7.6), P ϭ 0.005 vs. placebo] and increased postexercise heart rate recovery at 1 min [from 40.7 (SD 10.9) to 45.1 beats/min (SD 8.8), P ϭ 0.02 vs. placebo]. In trained athletes, pyridostigmine did not change resting heart rate or postexercise heart rate recovery when compared with placebo. Time-and frequency-domain indexes of resting heart rate variability did not differ after pyridostigmine versus placebo in either cohort and were not significantly associated with postexercise heart rate recovery in either cohort. The divergent effects of pyridostigmine on resting and postexercise measures of cardiac parasympathetic function in sedentary subjects confirm that these measures characterize distinct aspects of cardiac parasympathetic regulation. The lesser effect of pyridostigmine on either measure of cardiac parasympathetic tone in the trained athletes indicates that the enhanced parasympathetic tone associated with exercise training is at least partially attributable to adaptations in the efferent parasympathetic pathway. heart rate variability; heart rate recovery; parasympathetic nervous system; exercise RESTING HEART RATE VARIABILITY and postexercise heart rate recovery are used in human studies to assess cardiac parasympathetic tone (1,30,47). The high-frequency (HF) component of resting heart rate variability quantifies short-term changes in heart rate caused by the effects of central and peripheral respiratory reflexes on vagal efferent activity during a resting steady state with low sympathetic activation (1). Postexercise heart rate recovery assesses the complex interaction of baroreceptor and central command signals that mediate a rapid deceleration of heart rate in the setting of autonomic flux, profound exercise-induced sympathetic stimulation, and high minute ventilation (30).Parasympathetic efferent control of heart rate is ultimately mediated by cholinergic signaling at the sinoatrial node. Acetyl...
Objective: To characterise the effects of acetylcholinesterase inhibition with pyridostigmine on parasympathetic tone in patients with chronic heart failure (CHF). Design: Prospective randomised, double blind crossover trial. Setting: University hospital outpatient heart failure clinic. Patients: 20 ambulatory subjects with stable CHF (mean age 55 years, mean ejection fraction 24%). Interventions: Oral administration of a single dose of pyridostigmine 30 mg and matching placebo on separate days. Main outcome measures: Heart rate recovery at one minute and three minutes after completion of maximal exercise. Results: Heart rate recovery at one minute after exercise was significantly greater after administration of pyridostigmine than after administration of placebo (mean (SEM) 27.4 (3.2) beats/min v 22.4 (2.4) beats/min, p < 0.01). Heart rate recovery at three minutes after exercise did not differ after administration of pyridostigmine and placebo (mean (SEM) 44.4 (3.9) beats/min v 41.8 (3.6) beats/ min, NS). Peak heart rate, peak oxygen uptake, peak respiratory exchange ratio, plasma noradrenaline (norepinephrine) concentrations, and plasma brain natriuretic peptide concentrations did not differ after administration of pyridostigmine and placebo. Conclusions: Acetylcholinesterase inhibition with pyridostigmine increased heart rate recovery at one minute but not at three minutes after exercise. A specific effect of pyridostigmine on heart rate one minute after exercise suggests that pyridostigmine augments parasympathetic tone in patients with CHF.
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