An Integrative Literature Review of Heart Rate Variability Measures to Determine Autonomic Nervous System Responsiveness Using Pharmacological Manipulation

BACKGROUND: Heart rate variability (HRV) is defined as the difference in the timing of intervals between successive heartbeats and is used as a surrogate measure to the responsiveness of the autonomic nervous system. A review and synthesis of HRV as an indicator of autonomic nervous system responsiveness to pharmacologic stimulation/blockade of sympathetic and/or parasympathetic nervous system branches have not been completed. PURPOSE: The aim of this integrative review is to synthesize research examining pharmacological modulation of the autonomic nervous system and the response of time domain, frequency domain, and nonlinear measures of HRV. CONCLUSIONS: Sympathetic nervous system blockade resulted in a consistent decrease in the standard deviation of normal-normal interval metric across studies. Stimulation of the parasympathetic nervous system was associated with an increase in several time, frequency, and nonlinear HRV indices, whereas blockade of the parasympathetic nervous system led to a decrease in similar indices. CLINICAL IMPLICATIONS: Recommendations to improve the reproducibility of future HRV research are provided for standardization of recording, analysis, and metric decisions and more thorough reporting of HRV indices in published studies. Alterations in autonomic nervous system input to the cardiovascular system are associated with an increased risk for adverse patient outcomes and increased mortality; therefore, understanding the influence of pharmacologic autonomic nervous system modulation on HRV indices and important considerations for reproducible HRV research design will inform future translational research on cardiovascular risk reduction.