title: Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations.
abstract: The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control.
authors.affiliation: Department of Medical Physics, School of Physics and Astronomy, Tel Aviv University, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Alcalay
authors.forename: S
authors.initials: S
authors.lastname: Izraeli
authors.forename: R
authors.initials: R
authors.lastname: Wallach-Kapon
authors.forename: Z
authors.initials: Z
authors.lastname: Tochner
authors.forename: Y
authors.initials: Y
authors.lastname: Benjamini
authors.forename: S
authors.initials: S
authors.lastname: Akselrod
mesh_terms: D000328:Adult; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods; D005583:Fourier Analysis; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D012016:Reference Values; D012119:Respiration / Q000187:drug effects; D012815:Signal Processing, Computer-Assisted; D016037:Single-Blind Method
chemical_list: D001285:Atropine