Assessment of Baroreflex Sensitivity and its Interaction with Cerebral Pressure-flow Dynamics

Abstract

Abstract

Assessment of baroreflex sensitivity (BRS) is used extensively in research to study neural regulation of cardiovascular function, and BRS estimation offers a potential diagnostic and prognostic utility in pathologies such as cardiovascular disease, stroke and diabetes. However, as differences between methods can potentially lead to inconsistent results, and some techniques are impractical for the clinical environment, uptake in the clinical arena has been limited. Nevertheless, there is a clear need for a simple physiological approach to facilitate BRS assessment. Hence, this thesis sought to examine the performance characteristics of the recently introduced sit-to-stand method, and through application of this method to further our understanding of baroreflex physiology. This thesis also explored relationships between baroreflex control of blood pressure and cerebral pressure-flow dynamics.

The test re-test reliability of the sit-to-stand method was evaluated using three approaches (intraclass correlation coefficient, standard error of measurement and Pearson’s correlation coefficient), and compared to two established methods: the modified Oxford method and Valsalva manoeuvre. The intraclass correlation coefficient (ICC) and standard error of measurement (SEM) findings, established that the reliability of the repeated sit-to-stand method was suitable for use in the research and clinical environments, and that reliability was superior to the modified Oxford method and Valsalva manoeuvre. Bland-Altman analysis of BRS quantified by the repeated sit-to-stand method and modified Oxford method showed poor agreement between the two methods.

Further investigations found that BRS and baroreflex hysteresis exhibited frequency-dependent characteristics between 0.03 Hz and 0.1 Hz. During the sit-to-stand method, BRS was highest at 0.05 Hz, and while baroreflex hysteresis was observed in all participants at 0.1 Hz, hysteresis was not observed at 0.05 Hz. These findings raise the question whether a single number can comprehensively describe BRS, and challenge the notion that hysteresis is an innate property of the baroreflex.

Investigation into the influence of respiratory rate on BRS found no evidence to support the notion that slow breathing enhanced BRS per se. Rather, the findings suggested that respiratory induced BP oscillations at a slow breathing frequency (6 breaths min-1) simulated baroreflex frequency-dependence effects, and thus enhanced BRS. These observations highlight the importance of considering the rate of BP change when assessing BRS, and offer an explanation at least in part, for the disparity and lack of agreement observed between BRS methods.

Finally this thesis extended the use of an orthostatic challenge to explore cerebral pressure-flow dynamics. Cerebral autoregulation (CA) was quantified following transient hypertensive and hypotensive challenges evoked by squatting to standing (and vice versa), using Tiecks Autoregulation Index (ARI), and further explored using a lumped parameter Windkessel model. The findings showed that when indexed by ARI, the CA response to transient hypertensive and hypotensive challenges differed according to sex, where females exhibited asymmetry but males did not. The Windkessel model suggested that the behaviour of the cerebral vasculature following transient hypertensive and hypotensive challenges differed according to direction of BP change and sex.

Collectively this thesis has shown that the sit-to-stand method offers a reliable approach for BRS assessment, and one that is capable of capturing detailed knowledge of underlying baroreflex physiology in the research and potentially the clinical environment. The frequency-dependent nature of BRS may contribute in part, to the disparity between methods and inconsistent findings between studies. Finally, the observation that CA asymmetry differs between males and females offers the potential for CVD and stroke treatment regimes to be designed for males and females and is an area that merits further investigation.