[The effects of chronic beta-blocker administration on respiratory sinus arrhythmia]

The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. In some studies in which an increased RSA was reported, central vagotonic activity has been proposed. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. Twenty normal subjects (mean age 28 +/- 2 years) were randomized to receive a hydrophilic (nadolol, N), a lipophilic (metoprolol, M) beta-blocker and placebo (PL). After 1 week of therapy a spectral analysis was made of the variability in heart rate and systolic blood pressure (SBP) while they controlled their breathing at 16 breaths/min for a period of 5 min. The high frequency component was calculated for the RR interval (HF-RR, RSA measure) and SBP (HF-SBP), and the squared coherence (K2) and phase functions (phi HF) were assessed between RR and SBP fluctuations in the respiratory band (RR-SBP); a negative phi HF means that RR changes follow SBP changes. The alpha HF (an index of the baroreflex gain) was also calculated. Both beta-blockers increased the mean RR interval (PL 808 +/- 21, N 1054 +/- 30, M 1031 +/- 27 ms; p < 0.0001), HF-RR (PL 6.3 +/- 0.3, N 7.1 +/- 0.3, M 7.2 +/- 0.3 ln-ms2; p = 0.002) and alpha HF (PL 13.6 +/- 1.5, N 21.9 +/- 2.8, M 24.5 +/- 3.6 ms/mmHg; p < 0.002), and both modified phi HF (PL -0.23 +/- 0.05, N -0.02 +/- 0.05, M -0.03 +/- 0.04 s; p < 0.0001). No difference was found between N and M. Chronic beta-adrenergic blockade enhanced RSA and baroreflex gain and reduced the phase between the RR interval and SBP oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.