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

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.

Figures

Figure 1

Heart rate recovery (HRR, beats/min, mean with error bar indicating positive SEM) at one minute and three minutes after maximal exercise in 20 subjects with chronic heart failure after treatment with pyridostigmine (solid bars) or placebo (open bars). *pv placebo.