Evaluation of importance of central effects of atenolol and metoprolol measured by heart rate variability during mental performance tasks, physical exercise, and daily life in stable postinfarct patients.
BACKGROUND
Physical exercise and mental work cause alterations in cardiac autonomic control. beta-Blockers protect the heart against stress, and this effect may be in part centrally mediated. In this context, the lipophilicity of the drug would be clinically relevant.


RESULTS
Thirty postinfarct patients were randomized to receive 100 mg atenolol or 200 mg metoprolol CR in a double-blind, crossover manner, each for a 6-week period. Heart rate (HR) variability was used to study autonomic effects during mental and physical stress and to study circadian variations. Mean 24-hour HR decreased from 77 +/- 7 to 60 +/- 6 beats per minute after atenolol and to 62 +/- 6 beats per minute after metoprolol (P = .046). At baseline, mental performance tasks did not affect HR, but decreased HR variability (SDNN index from 51 +/- 26 to 30 +/- 13 milliseconds [ms], P < .001; high-frequency power from 130 +/- 143 to 110 +/- 125 ms2, P = .046; and low-frequency power from 538 +/- 447 to 290 +/- 275 ms2, P < .001). Both beta-blockers decreased HR during mental performance tasks (P < .001) and increased SDNN index and high-frequency power. Before treatment, bicycle exercise decreased HR variability; root-mean-square of successive difference decreased from 21 +/- 8 to 15 +/- 10 ms (P = .004). beta-Blockade could not prevent this decrease. No differences between atenolol and metoprolol were observed for absolute high- and low-frequency power or after adjustment for HR. Vagal blockade with methylatropine during chronic beta-blocker treatment nearly abolished all components of spectral power. HR was found to be the parameter most strongly affected by beta-blockade but not by an influence on vagal tone. No differences were found between atenolol and metoprolol.


CONCLUSIONS
In stable postinfarct patients, chronic treatment with metoprolol and atenolol attenuates the reduction in HR variability induced by mental performance tasks, but the effects during exercise are limited. beta-Blockers do not appear to increase vagal tone in this stable patient group. The point of action in these patients is mainly a reduction in HR, probably due to a reduction in stress-induced sympathetic activation. Clinically significant differences between atenolol and metoprolol were absent, indicating that the degree of lipophilicity does not distinguish among the beta-blockers what their salutary effects are on HR variability during the specific challenges used.
Thorax Center, University Hospital Groningen, The Netherlands.
Y S
YS
Tuininga
H J
HJ
Crijns
J
J
Brouwer
M P
MP
van den Berg
A J
AJ
Man in't Veld
G
G
Mulder
K I
KI
Lie
D000203:Activities of Daily Living; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D013312:Stress, Physiological / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D008790:Metoprolol