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 card iac autonomic control. beta-Blockers protect the heart against stress, and this effect may be in part centrally mediated. In this context, t he 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 stu dy autonomic effects during mental and physical stress and to study ci rcadian variations. Mean 24-hour HR decreased from 77+/-7 to 60+/-6 be ats per minute after atenolol and to 62+/-6 beats per minute after met oprolol (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 ms(2), P=.046; and low-frequency power from 538+/-447 to 290+/-2 75 ms(2), P<.001). Both beta-blockers decreased HR during mental perfo rmance tasks (P<.001) and increased SDNN index and high-frequency powe r. Before treatment, bicycle exercise decreased HR variability; root-m ean-square of successive difference decreased from 21+/-8 to 15+/-10 m s (P=.004). beta-Blockade could not prevent this decrease. No differen ces between atenolol and metoprolol were observed for absolute high- a nd 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 mo st strongly affected by beta-blockade but not by an influence on vagal tone. No differences were found between atenolol and metoprolol. Conc lusions In stable postinfarct patients, chronic treatment with metopro lol 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 pa tient group. The point of action in these patients is mainly a reducti on in HR, probably due to a reduction in stress-induced sympathetic ac tivation. Clinically significant differences between atenolol and meto prolol were absent, indicating that the degree of lipophilicity does n ot distinguish among the beta-blockers what their salutary effects are on HR variability during the specific challenges used.