Background: A shift of cardiac autonomic balance towards sympathetic marks a poor
prognosis in several diseases and has also been reported in COPD. Bronchodilators, beta-2
adrenergic agonists and anticholinergic drugs, are the mainstay of treatment of COPD. We
hypothesized that drugs belonging to these classes, respectively salbutamol and ipratropium, would
cause a sympathetic shift in cardiac autonomic activity as a consequence of their pharmacological
Objective: To study the effect of ipratropium and salbutamol on Heart Rate variability in COPD.
Methods: Thirty-three stable ex-smoker, inpatient-male COPD patients were included in a doubleblind,
placebo-controlled single-dose randomized study. After baseline spirometry, cardiac
autonomic activity was measured using Heart Rate Variability (HRV) that yields several measures of
parasympathetic and sympathetic activity. The patients randomly received placebo, salbutamol
(200μg) or ipratropium (80µg) by inhalation on three consecutive days. After half an hour, HRV
measurements and spirometry were repeated. The average heart rate, and various time and frequency
domain parameters were obtained using non-parametric Fast Fourier Transform (FFT) algorithm.
Results: Ipratropium decreased the resting heart rate by 2.5% while salbutamol increases it by
approximately 6%. Salbutamol resulted in a significant decrease in normalized high frequency
variability (HFnu), a marker of parasympathetic activity, and increase in normalized low frequency
variability (LFnu) that marks sympathetic activity, and the LF/HF ratio indicating a sympathetic shift
of autonomic balance. Ipratropium had no effect on HRV parameters. The study shows that a single
inhalation of 200 µg salbutamol shifts cardiac autonomic control towards increased sympathetic
activity whereas ipratropium does not.
Conclusion: Inhalation of salbutamol causes a sympathetic shift in the cardiac autonomic balance.