Paradoxical pharmacodynamic effect of atropine on parasympathetic control: A study by spectral analysis of heart rate fluctuations

Menachem Alcalay, Shai Izraeli, Ruti Wallach-Kapon, Zelig Tochner, Yoav Benjamini, Solange Akselrod

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)518-527
Number of pages10
JournalClinical Pharmacology and Therapeutics
Volume52
Issue number5
StatePublished - Nov 1992

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