Short-term effects of inhaled salbutamol on autonomic cardiovascular control in healthy subjects: a placebo-controlled study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Previous reports have demonstrated a link between inhaled beta(2)-agonist use and cardiovascular morbidity and mortality. center dot The underlying mechanism for this relationship, however, remains controversial. WHAT THIS STUDY ADDS center dot Inhalation of a therapeutic dose of salbutamol resulted in significant haemodynamic changes, which were accompanied by a shift in cardiovascular autonomic tone towards increased sympathetic outflow in the absence of baroreceptor activation. center dot The observed changes in cardiac autonomic function may contribute to an increased cardiac risk associated with inhaled beta(2)-agonist treatment. To investigate short-term effects of inhaled salbutamol on haemodynamic changes and cardiovascular autonomic control. A randomized, single-blinded, placebo-controlled study of 0.2 mg of inhaled salbutamol was conducted on 12 healthy nonsmoking volunteers with a mean age of 24 +/- 2 years at two different testing sessions. Non-invasively obtained continuous haemodynamic measurements of cardiac output, beat-to-beat arterial blood pressure, and total peripheral resistance were recorded prior to and for a total of 120 min after inhalation of the respective study drug. Continuous cardiovascular autonomic tone was recorded using power spectral analysis of heart rate and blood pressure variability. Spontaneous baroreceptor activity was assessed by the sequence method. There were no significant changes in any of the baseline parameters between the different testing sessions. Inhalation of salbutamol caused a significant increase in cardiac output from 6.7 +/- 1.3 to 7.7 +/- 1.4 l min(-1) (P < 0.05), and a decrease in total peripheral resistance from 1076 +/- 192 to 905 +/- 172 dyne s(-1) cm(-5) (P < 0.05) within 15 min after inhalation. Moreover, salbutamol significantly increased sympathetically mediated low-frequency heart rate variability (P < 0.01), whereas parasympathetically mediated high-frequency heart rate variability decreased (P < 0.01). All changes persisted for approximately 30 min and were fully reversible at 120 min. There were no significant changes in systolic blood pressure variability or spontaneous baroreceptor activity. Inhalation of therapeutic doses of salbutamol in healthy subjects resulted in significant haemodynamic changes and a shift of sympathovagal balance towards increased sympathetic tone in the absence of baroreceptor activation.