Cardiac and baroreflex responses: : from tilt table to gated auricular Vagus Nerve Stimulation

Abstract

The variability of the heart rate and its response to external stimuli has long been of clinical importance. Recently the cardiovagal baroreflex sensitivity BRS has been investigated as an additional diagnostic tool for a number of diseases. Traditionally BRS was estimated using linear regression, a more recent method uses a best _t ellipse approximation. Auricular vagus nerve stimulation (aVNS) is a non-invasive neuromodulatory therapy for a number of chronic illnesses. To achieve a more individualized treatment closed-loop aVNS systems, synchronised to patients vital signals, are being developed and tested.In this work two different sets of experiments were conducted to investigate the effects of external stimuli on the human cardiovascular system. Firstly the BRS was investigated in various head up tilt body positions, from supine, 30°, 60°, 80° head up tilt to the standing position. Seven subjects voluntarily participated and slow paced breathing was employed throughout to exaggerate heart rate variability and the baroreflex. The results were searched for continuous sequences of rising and falling heart rate variability RR and systolic blood pressure PS, representing the cardiovagal baroreflex, then analysed using both a best _t ellipse method and linear regression.The second experiment investigated the effect of synchronised auricular vagus nerve stimulation. Measurements were conducted following two different protocols, the first using cardiac gated aVNS, the second respiratory gated aVNS. Five subjects volunteered, with each subject participating twice for a total of 10 measurements per protocol. The recorded blood pressure and ECG data was analysed in both time and frequency domain. The results show significant differences in the estimated BRS between different head up tilt positions. The ellipse method resulted in median values of 28, 19.8, 11.9, 11.5 and 11.2 ms/mmHg for supine, 30°, 60°, 80° and standing, a mirrored trend also seen in the linear regression. A detailed beat by beat analysis also confirmed a lower BRS for the more upright positions, with significantly higher BRS changes recorded during expiration than inspiration and thereby confirming the baroreflex hysteresis. Of the aVNS experiments only the respiratory gated experiment recorded any significant changes. Here the inspiration synced aVNS showed an increasing trend in the root mean square of successive differences between normal heartbeats RMSSD over the non aVNS baseline, indicating an increased high frequency content in the heart rate variability. Additionally the respiration rate dropped for both inspiratory and expiratory synchronised aVNS.Overall the head up tilt experiment provided new insight into BRS response, the resulting estimates comparable to other studies. While the aVNS experiments were likely too short for significant results, the trends in the respiration gated aVNS do show promise for further study.