Do the high-frequency indexes of HRV provide a faithful assessment of cardiac vagal tone? A critical theoretical evaluation

When spectral analysis of the heart rate (HR) signal is performed, it is quite common to attribute the HF indexes of heart rate variability (HRV) to cardiac vagal control. The paradigm underlying this attribution states that changes in cardiac vagal outflow correspond to a proportional change in respiratory sinus arrhythmia (RSA). However, recent studies have demonstrated that variations in these indexes do not necessarily reflect proportional changes in vagal tone. The current study provides a theoretical evaluation of the relationship between mean HR, RSA, and cardiac vagal tone. This evaluation is based on a theoretical model, which quantifies the differential effects of vagal blockade by a competitive muscarinic antagonist on the HF indexes of HRV. The model relies on several assumptions that reflect the basic physiology of the sinoatirial (SA) node, as well as pharmacological relations that describe agonist/antagonist equilibrium at the SA receptors. The mathematical framework of this model is the integral-pulse-frequency-modulation (IPFM) process, and its derivations lead to a specific expressions for the dependence of HF and mean HR on the level of vagal blockade. These expressions provide a new insight into the relationship between mean HR, RSA, and vagal tone, and explain conflicting experimental results previously published.