Revisiting the Sequence Method for Baroreflex Analysis

The sequence method is an important approach to assess the baroreflex function, mainly because it is based on the spontaneous fluctuations of beat-by-beat arterial pressure (for example, systolic arterial pressure or SAP) and pulse interval (PI). However, some studies revealed that the baroreflex effectiveness index (BEI), calculated through the sequence method, shows an intriguing oscillatory pattern as function of the delay between SAP and Pl. It has been hypothesized that this pattern is related to the respiratory influence on SAP and/or PI variability, limiting the SAP ramps to 3 or 4 beats of length. In this study, this hypothesis was tested by assessing the sequence method using raw (original) and filtered series. Results were contrasted to the well-established transfer function, estimated between SAP and Pl. Continuous arterial pressure recordings were obtained from healthy rats (N = 61) and beat-by-beat series of SAP and PI were generated. Low-pass (LP) and high-pass (HP) filtered series of SAP and PI were created by filtering the original series with a cutoff frequency of 0.8 Hz. Original series were analyzed by either the sequence method or cross-spectral analysis (transfer function) at low- (LF) and high- (HF) frequency bands, while filtered series were evaluated only by the sequence method. Baroreflex sensitivity (BRS) and BEI of original series, calculated by sequence method, was highly (85-90%) determined by HP series, with no significant association between original and LP series. A high correlation (> 0.7) was found between the BRS estimated from original series (sequence method) and HF band (transfer function), as well as for LP series (sequence method) and LF band (transfer function). These findings confirmed the hypothesis that the sequence method quantifies only the high-frequency components of the baroreflex, neglecting the low-frequency influences, such as the Mayer waves. Therefore, we propose using both the original and LP filtered time series for a broader assessment of the baroreflex function using the sequence method.