β-Blocker Effects on Respiratory Sinus Arrhythmia and Baroreflex Gain in Normal Subjects

¹ From the Institute of Cardiology, University of Bari, Bari, Italy, and the "Salvatore Maugeri" Foundation IRCCS, Cassano Medical Centre, Cassano, Italy

Study objective: The results of studies on the effect of β-adrenergie blockade on respiratory sinus arrhythmia (RSA) are discordant. The aim of this study was to verify whether chronic β-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral.

Participants and design: Twenty normal subjects (28±2 years old) were randomized to receive a hydrophilic (nadolol) β-blocker, a lipophilic (metoprolol) β-blocker, and placebo.

Measurements: After 1 week of therapy, a spectral analysis was made of the variability in heart rate and systolic BP during controlled breathing at 16 breaths/min. The high-frequency component was calculated for the RR interval (measure of RSA) and systolic pressure, and the squared coherence and phase functions were assessed between RR and systolic pressure fluctuations in the respiratory band; a negative phase means that RR changes follow systolic pressure changes. The gain in the relationship between the two signal fluctuations was also calculated.

Results: Both β-blockers increased the mean (±SD) RR interval (placebo=808±21, nadolol=1,054±30, metoprolol=1,031±27 ms; p<0.0001), RSA (placebo=542, nadolol=1,177, metoprolol 1,316 ms²; p=0.002), and the gain (placebo=13.6±1.5, nadolol=21.9±2.8, metoprolol=24.5±3.6 ms/mm Hg; p<0.002), and both modified the phase function (placebo=21.1±5.3, nadolol=1.8±4.9, metoprolol=2.9±4.2 degree; p<0.0001). No difference was found between nadolol and metoprolol.

Conclusions: Chronic β-adrenergic blockade enhanced both RSA and baroreflex gain and reduced the phase between the RR interval and systolic pressure oscillations. Since no difference was found between the hydrophilic and the lipophilic β-blockers, these changes seem to be due to a peripheral effect.

Key Words: baroreflex sensitivity • cross-spectral analysis • humans • hydrophilic β-blockers • lipophilic β-blockers • metoprolol • nadolol • respiratory sinus arrhythmia • vagal activity

Submitted on July 24, 1997
Accepted on December 1, 1997

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