Titre du document / Document title

Evaluation of the effect on heart rate variability of some agents acting at the β-adrenoceptor using nonlinear scatterplot and sequence methods

Auteur(s) / Author(s)

SILKE B. ⁽¹⁾ ; RIDDELL J. G. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Therapeutics and Pharmacology, The Whitla Division of Medicine, The Queen's University of Belfast, Medical Biology Centre, Belfast, IRLANDE

Résumé / Abstract

There is evidence that the processes regulating heart rate variability (HRV) reflect nonlinear complexity and show chaotic' determinism. Data analyses using nonlinear methods may therefore reveal patterns not apparent with the standard methods for HRV analysis. We have consequently used two nonlinear methods, the Poincare plot (scatterplot) and cardiac sequence (quadrant) analysis, in addition to the standard time-domain summary statistics, during a normal volunteer investigation of the effects on HRV of some agents acting at the cardiac beta-adrenoceptor. Under double-blind and randomized conditions (Latin square design), 25 normal volunteers received placebo, salbutamol 8 mg (β₂-adrenoceptor partial agonist), pindolol 10 mg (β₂-adrenoceptor partial agonist), or atenolol 50 mg (β₁-adrenoceptor antagonist). Single oral doses of medication (at weekly intervals) were administered at 22:30 hours, with sleeping heart rates recorded overnight. The long-term (SDNN, SDANN) and short-term (rMSSD) time-domain summary statistics were reduced by salbutamol 8 mg and increased by atenolol 50 mg compared with placebo. The reductions in both SDNN and SDANN were greater after salbutamol 8 mg compared with pindolol 10 mg. The reduced HRV after pindolol 10 mg differed from the increased HRV following atenolol 50 mg. The Poincaré plot, constructed by plotting each RR interval against the preceding RR interval, was measured using a reproducible computerized method. Scatterplot length and area were reduced by salbutamol 8 mg and increased by atenolol 50 mg compared with placebo; scatterplot length and area were lower after pindolol 10 mg compared with atenolol 50 mg. Geometric analysis of the scatterplots allowed width assessment (i.e., dispersion) at fixed RR intervals. At the higher percentiles (i.e., 90% of scatterplot length: low HR), salbutamol 8 mg reduced and atenolol 50 mg increased dispersion; at lower percentiles (i.e., 10%, 25%, and 50% length), atenolol 50 mg and pindolol 10 mg increased dispersion compared with placebo and salbutamol 8 mg. Cardiac sequence analysis (differences between three adjacent beats; ΔRR vs. ΔRR_n+1) was used to assess the short-term patterns of cardiac acceleration and deceleration. Four patterns were identified: +/+ (a lengthening sequencing), +/- or -/+ (balanced sequences), and finally -/- (a shortening sequence). Cardiac acceleration episodes (i.e., number of times ARR and ΔRR_n+1 were both changed) were increased in quadrants -/- and +/+ following pindolol 10 mg and salbutamol 8 mg; the beat-to-beat difference (ΔRR_n+1) was reduced after salbutamol 8 mg compared with the three other groups. These results demonstrated a shift towards sympathetic dominance (β-adrenoceptor partial agonist salbutamol 8 mg) or parasympathetic dominance (β₁-adrenoceptor antagonist atenolol 50 mg); pindolol 10 mg exhibited HR-dependent effects, reducing HRV at low but increasing variability at high prevailing heart rates. These nonlinear methods appear to be valuable tools to investigate HRV in health and to study the implications of perturbation of HRV with drug therapy in disease states.

Revue / Journal Title

Cardiovascular drugs and therapy   ISSN 0920-3206   CODEN CDTHET 

Source / Source

1998, vol. 12, n^o5, pp. 439-448 (44 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Dordrecht, PAYS-BAS  (1987) (Revue)

Mots-clés anglais / English Keywords

Heart rate ; Mechanism of action ; β-Adrenergic receptor ; Heart ; Myocardium ; Circulatory system ; Variability ; Human ; Normal ; Randomization ; Double blind study ; Placebo ; Single dose ; Oral administration ; Methodology ; Statistical analysis ; Non linear model ;

Mots-clés français / French Keywords

Rythme cardiaque ; Mécanisme action ; Récepteur β-adrénergique ; Coeur ; Myocarde ; Appareil circulatoire ; Variabilité ; Homme ; Normal ; Randomisation ; Etude double insu ; Placebo ; Dose unique ; Voie orale ; Méthodologie ; Analyse statistique ; Modèle non linéaire ;

Mots-clés espagnols / Spanish Keywords

Ritmo cardíaco ; Mecanismo acción ; Receptor β-adrenérgico ; Corazón ; Miocardio ; Aparato circulatorio ; Variabilidad ; Hombre ; Normal ; Aleatorización ; Estudio doble ciego ; Placebo ; Dosis única ; Vía oral ; Metodología ; Análisis estadístico ; Modelo no lineal ;

Localisation / Location

INIST-CNRS, Cote INIST : 21146, 35400007404503.0040