Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic heart failure

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Abstract
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.