High-frequency autonomic modulation: a new model for analysis of autonomic cardiac control

Br J Pharmacol. 2018 Aug;175(15):3131-3143. doi: 10.1111/bph.14354. Epub 2018 Jun 15.


Background and purpose: Increase in high-frequency beat-to-beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co-activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed.

Experimental approach: High-frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking and non-smoking subjects.

Key results: Three states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high-frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs, whereas smoking caused an increase in S3 oscillations.

Conclusions and implications: The combined analysis of the magnitude of high-frequency heart rate and high-frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity.

MeSH terms

  • Adult
  • Animals
  • Autonomic Nervous System*
  • Dogs
  • Electrocardiography
  • Female
  • Heart / physiology*
  • Heart Rate
  • Humans
  • Macaca fascicularis
  • Male
  • Middle Aged
  • Models, Cardiovascular*
  • Young Adult