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

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

Author information

1
Centre de Recherches Biologiques, CERB, Baugy, 18800, France.
2
Department of Internal Medicine, Hopital Lapeyronie, Montpellier, France.
3
Laboratoire PHYMEDEXP,INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier Cedex 05, 34295, France.

Abstract

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.

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