Beta-blocker effects on respiratory sinus arrhythmia and baroreflex gain in normal subjects.
OBJECTIVE
The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. 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.


METHODS
Twenty normal subjects (28+/-2 years old) were randomized to receive a hydrophilic (nadolol) beta-blocker, a lipophilic (metoprolol) beta-blocker, and placebo.


METHODS
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 beta-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 beta-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 beta-blockers, these changes seem to be due to a peripheral effect.
Institute of Cardiology, University of Bari, Italy.
M V
MV
Pitzalis
F
F
Mastropasqua
F
F
Massari
A
A
Passantino
P
P
Totaro
C
C
Forleo
P
P
Rizzon
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D001146:Arrhythmia, Sinus / Q000188:drug therapy*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D009248:Nadolol / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D012119:Respiration / Q000502:physiology*; D012815:Signal Processing, Computer-Assisted; D016037:Single-Blind Method; D013599:Systole; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D010919:Placebos; D009248:Nadolol; D008790:Metoprolol