HEART-RATE-VARIABILITY EFFECTS OF AN AGONIST OR ANTAGONISTS OF THE BETA-ADRENOCEPTOR ASSESSED WITH SCATTERPLOT AND SEQUENCE-ANALYSIS

There is evidence that the processes regulating heart rate variations reflect non-linear complexity and show 'chaotic' determinism. Data ana lyses using non-linear methods may therefore reveal patterns not appar ent with conventional statistical approaches. We have consequently inv estigated two non-linear methods, the Poincare plot (scatterplot) and cardiac sequence (quadrant) analysis, and compared these with standard time-domain summary statistics, during a normal volunteer investigati on of an agonist and antagonists of the cardiac beta-adrenoceptor. Und er double-blind and randomized conditions (Latin square design), 12 no rmal volunteers received placebo, celiprolol (beta(1)- and beta(2)-adr enoceptor partial agonist), propranolol (beta(1)- and beta(2)-adrenoce ptor antagonist), atenolol (beta(1)-adrenoceptor antagonist) and combi nations of these agents. Single oral doses of medication (at weekly in tervals) were administered at 22:30 h with sleeping heart rates record ed overnight. The long (SDNN, SDANN) and short-term (rmsSD) time-domai n summary statistics were reduced by celiprolol - effects different fr om the unchanged or small increases after atenolol and propranolol alo ne. The Poincare plot was constructed by plotting each RR interval aga inst the preceding RR interval, but unlike previous descriptions of th e method, an automated computer method, with a high level of reproduci bility, was employed. Scatterplot length and area were reduced followi ng celiprolol and different from the small increases after propranolol and atenolol. The geometric analysis of the scatterplots allowed widt h assessment (i.e. dispersion) at fixed RR intervals. Differences betw een the drugs were confined to the higher percentiles (i.e. 75% and 90 % of scatterplot length: low heart rate). The long-term time-domain st atistics (SDNN, SDANN) correlated best with scatterplot length and are a whereas the short-term heart rate variability (HRV) indices (rmsSD, pNN(50)) correlated strongly with scatterplot width. Cardiac sequence analysis (differences between three adjacent beats; Delta RR vs Delta RRn+1) assessed the short-term patterns of cardiac acceleration and de celeration, four patterns are identified: +/+ (a lengthening sequencin g), +/- or -/+ (balanced sequences), and finally -/- (a shortening seq uence). A running count of events by quadrant, together with the avera ge magnitude of the differences was computed. The beta-adrenoceptor pa rtial agonist celiprolol increased acceleration sequences. The duratio n of beat-to-beat difference shortened after celiprolol; this contrast ed with increased duration of beat-to-beat difference after propranolo l and atenolol. These results demonstrated a shift towards sympathetic dominance after the beta-adrenoceptor partial agonist celiprolol cont rasting with parasympathetic dominance after the beta-adrenoceptor ant agonists propranolol and atenolol. These non-linear methods appear to be valuable tools to investigate HRV in health and in cardiovascular d isease and to study the implications of alterations in autonomic contr ol during therapeutic intervention. Clin Auton Res 8:145-153 (C) 1998 Lippincott-Raven Publishers.