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.

Methods and 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.