Pharmacological modulation of vagal cardiac control measured by heart rate power spectrum: A possible bioequivalent probe

The autonomic cardiac control was studied as a sensitive parameter of anticholinergic treatment in humans, using heart-rate (HR) power spectrum. A cross-over placebo controlled study was performed in 8 young volunteers who received increasing bolusdoses of IV atropine (from 1.3 μg/kg to 29.9 μg/kg) or placebo. Computing the HR power spectrum and integrating over specific frequency bands, we focused in particular on the respiratory frequency band (usually between 0.2-0.4 Hz) which is purely of vagal mediation. At small atropine doses (<5.2 μg/kg), the respiratory peak increased, relative to baseline, with maximal response at 2.6 μg/kg (from 1.0 to 1.9 ± 0.9). Larger doses of atropine (≥6.5 μg/kg) reduced the power of the respiratory peak, by a few orders of magnitude, in a dose-dependent way. Corresponding changes were observed in mean HR but in the opposite direction i.e., a maximal bradycardia at 2.6 μg/kg and a nearly two fold increase in mean HR at 29.9 μg/kg. We conclude that atropine has a bimodal dose-dependent effect on parasympathetic cardiac control. Since the use of HR spectral analysis has been demonstrated in various animal species, we suggest that it can be used as a sensitive noninvasive probe for animal to man transformation studies.