Journal of Clinical Trials
Open Access

Abstract

Impaired Signaling Intrinsic to Sinoatrial Node Pacemaker Cells Affects Heart Rate Variability during Cardiac Disease

Yael Yaniv, Alexey E Lyashkov and Edward G Lakatta

The normal heart beat intervals are neither strictly stationary nor completely random, and continuously shift from one period to another. Decoding the ECG identifies this “hidden” information that imparts inherent complexity to the heart-beating interval time series. Loss of this complexity in cardiovascular disease is manifested as a reduction in Heart Rate Variability (HRV) and this reduction correlates with an increase in both morbidity and mortality. Because HRV measurements are noninvasive and easy to perform, they have emerged as an important tool in cardiology. However, the identities of specific mechanisms that underline the changes in HRV that occur in cardiovascular diseases remain largely unknown. Changes in HRV have mainly been interpreted on a neural basis, i.e. due to changes in autonomic impulses to the heart: sympathetic activity decreases both the average heart beat interval and HRV, and parasympathetic activity increases both. It has now become clear, however, that the heart rate and HRV are also determined by intrinsic properties of the pacemaker cells that comprise the sinoatrial node, and the responses of these properties to autonomic receptor stimulation. Here we review how
changes in the properties of coupled-clock mechanisms intrinsic to pacemaker cells that comprise the sinoatrial node and their impaired response to autonomic receptor stimulation are implicated in the changes of HRV observed in heart diseases.