Abstract
Heart rate variability (HRV), the beat-to-beat variation in either heart rate (HR) or heart period (R-R interval), has become a popular clinical and investigational tool to quantify cardiac autonomic regulation. However, it is not widely appreciated that, due to the inverse curvilinear relationship between HR and R-R interval, HR per se can profoundly influence HRV. It is, therefore, critical to correct HRV for the prevailing HR particularly, as HR changes in response to autonomic neural activation or inhibition. The present study evaluated the effects of HR on the HRV response to autonomic interventions that either increased (submaximal exercise, n = 25 or baroreceptor reflex activation, n = 20) or reduced (pharmacological blockade: β-adrenergic receptor, muscarinic receptor antagonists alone and in combination, n = 25, or bilateral cervical vagotomy, n = 9) autonomic neural activity in a canine model. Both total (RR interval standard deviation, RRSD) and the high frequency (HF) variability (HF, 0.24–1.04 Hz) were determined before and in response to an autonomic intervention. All interventions that reduced or abolished cardiac parasympathetic regulation provoked large reductions in HRV even after HR correction [division by mean RRsec or (mean RRsec)2 for RRSD and HF, respectively] while interventions that reduced HR yielded mixed results. β-adrenergic receptor blockade reduced HRV (RRSD but not HF) while both RRSD and HF increased in response to increases in arterial blood (baroreceptor reflex activation) even after HR correction. These data suggest that the physiological basis for HRV is revealed after correction for prevailing HR and, further, that cardiac parasympathetic activity is responsible for a major portion of the HRV in the dog.
Highlights
Heart rate variability (HRV, beat-to-beat changes in the heart period, R-R interval) is increasingly used to quantify cardiac autonomic regulation and to identify patients at an increased risk for adverse cardiovascular events (Appel et al, 1989; Task Force of the European Society of Cardiology, and the North American Society of Pacing and Electrophysiology, 1996; Berntson et al, 1997; Denver et al, 2007; Thayler et al, 2010; Billman, 2011, 2013)
Frequency domain analysis of HRV is affected by mean heart rate (HR)
After correction for HR, vagotomy still produced significant reductions in both corrected R-R interval (P < 0.0002, Figure 9A) and corrected high frequency (HF) variability (P < 0.05, Figure 9B). These results are very similar to those obtained following treatment with atropine sulfate and further demonstrate that cardiac parasympathetic activity is responsible for a major portion of the HRV, independent of changes in the prevailing HR
Summary
Heart rate variability (HRV, beat-to-beat changes in the heart period, R-R interval) is increasingly used to quantify cardiac autonomic regulation and to identify patients at an increased risk for adverse cardiovascular events (Appel et al, 1989; Task Force of the European Society of Cardiology, and the North American Society of Pacing and Electrophysiology, 1996; Berntson et al, 1997; Denver et al, 2007; Thayler et al, 2010; Billman, 2011, 2013). It is not widely appreciated that the prevailing heart rate (HR) can influence HRV independent of changes in cardiac autonomic regulation. As a consequence of the inverse curvilinear relationship between HR and R-R interval, identical changes in HR will elicit profoundly different changes in the R-R interval variability depending upon the baseline HR (Sacha and Pluta, 2008). It is essential to correct HRV for the prevailing HR in order to identify physiological (changes in cardiac autonomic regulation), as opposed to artifactual (that merely arise as a consequence of a mathematical relationship), changes in HRV
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