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

Abstract

Aims: To investigate short-term effects of inhaled salbutamol on haemodynamic changes and cardiovascular autonomic control.

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1

Short-term effects of inhaled salbutamol on cardiac output measurements. T5, T15, T30, T90, indicating 5, 15, 30 or 90 min after inhalation of the study drugs, respectively. *P < 0.05 for salbutamol vs. placebo inhalation. Salbutamol (——); Placebo (······)

Figure 2

Short-term effects of inhaled salbutamol on total peripheral resistance. T5, T15, T30, T90, indicating 5, 15, 30 or 90 min after inhalation of the study drugs, respectively. *P < 0.05 for salbutamol vs. placebo inhalation. Salbutamol (——); Placebo (······)

Figure 3

Original tracing from a representative subject during normal breathing and after inhalation of a single therapeutic dose of salbutamol. Drug inhalation resulted in a significant increase in LF-HRV indicating a shift of autonomic tone towards increased sympathetic activity. Peaks are indicated by arrows. LF-HRV and HF-HRV, low-frequency and high-frequency heart rate variability expressed as normalized units. T15, T30, 15 or 30 min after inhalation of the study drug, respectively

Figure 4

Original record of the relationship between pulse interval (PI) and systolic blood pressure (SBP) in a healthy subject at baseline, 5 (T5), 15 (T15) and 30 (T30) min after inhalation of salbutamol. N, total number of identified spontaneous baroreceptor sequences