title: Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamics.
abstract: Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland.
authors.forename: M P
authors.initials: MP
authors.lastname: Tulppo
authors.forename: T H
authors.initials: TH
authors.lastname: Mäkikallio
authors.forename: T
authors.initials: T
authors.lastname: Seppänen
authors.forename: K
authors.initials: K
authors.lastname: Shoemaker
authors.forename: E
authors.initials: E
authors.lastname: Tutungi
authors.forename: R L
authors.initials: RL
authors.lastname: Hughson
authors.forename: H V
authors.initials: HV
authors.lastname: Huikuri
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D004338:Drug Combinations; D004837:Epinephrine / Q000494:pharmacology*; D017709:Fractals; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D009407:Nerve Block; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004338:Drug Combinations; D001285:Atropine; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine