Increase in high-frequency (HF) 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 (HRV) analysis. The present work aimed to find a translational model that would allow this particular state of heart rate autonomic control to be assessed.
HF heart rate (HFHR) and heart period (HFRR) oscillations were analyzed within discrete 10-second intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs with respect to pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking versus non-smoking subjects.
Three states of autonomic modulation, named S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of HRV named High-Frequency Autonomic Modulation (HFAM). S2 was demonstrated to correspond to a specific state during which both parasympathetic and sympathetic systems are coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs whereas smoking caused an increase in S3 oscillations.
The combined analysis of the magnitude of HFHR and HFRR oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new avenues for the assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity.
Pharmacology, Toxicology and Pharmaceutical Science
4
10%
Medicine and Dentistry
4
10%
Unspecified
3
7%
Nursing and Health Professions
3
7%
Agricultural and Biological Sciences
3
7%
Other
11
27%
Unknown
13
32%
Attention Score in Context
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