Baroreflex sensitivity measured by pulse photoplethysmography

Novel methods for assessing baroreflex sensitivity (BRS) using only pulse photoplethysmography (PPG) signals are presented. Proposed methods were evaluated with a data set containing electrocardiogram (ECG), blood pressure (BP), and PPG signals from 17 healthy subjects during a tilt table test. The methods are based on a surrogate of a index, which is defined as the power ratio of RR interval variability (RRV) and that of systolic arterial pressure series variability (SAPV). The proposed a index surrogates use pulse-to-pulse interval series variability (PPV) as a surrogate of RRV, and different morphological features of the PPG pulse which have been hypothesized to be related to BP, as series surrogates of SAPV. A time-frequency technique was used to assess BRS, taking into account the non-stationarity of the protocol. This technique identifies two time-varying frequency bands where RRV and SAPV (or their surrogates) are expected to be coupled: the low frequency (LF, inside 0.04–0.15 Hz range), and the high frequency (HF, inside 0.15–0.4 Hz range) bands. Furthermore, time-frequency coherence is used to identify the time intervals when the RRV and SAPV (or their surrogates) are coupled. Conventional a index based on RRV and SAPV was used as Gold Standard. Spearman correlation coefficients between conventional a index and its PPG-based surrogates were computed and the paired Wilcoxon statistical test was applied in order to assess whether the indices can find significant differences (p < 0.05) between different stages of the protocol. The highest correlations with the conventional a index were obtained by the a-index-surrogate based on PPV and pulse up-slope (PUS), with 0.74 for LF band, and 0.81 for HF band. Furthermore, this index found significant differences between rest stages and tilt stage in both LF and HF bands according to the paired Wilcoxon test, as the conventional a index also did. These results suggest that BRS changes induced by the tilt test can be assessed with high correlation by only a PPG signal using PPV as RRV surrogate, and PPG morphological features as SAPV surrogates, being PUS the most convenient SAPV surrogate among the studied ones

Assessment Of Blood Pressure Regulatory Controls To Detect Hypovolemia And Orthostatic Intolerance

Regulation of blood pressure is vital for maintaining organ perfusion and homeostasis. A significant decline in arterial blood pressure could lead to fainting and hypovolemic shock. In contrast to young and healthy, people with impaired autonomic control due to aging or disease find regulating blood pressure rather demanding during orthostatic challenge. This thesis performed an assessment of blood pressure regulatory controls during orthostatic challenge via traditional as well as novel approaches with two distinct applications 1) to design a robust automated system for early identification of hypovolemia and 2) to assess orthostatic tolerance in humans. In chapter 3, moderate intensity hemorrhage was simulated via lower-body negative pressure (LBNP) with an aim to identify moderate intensity hemorrhage (-30 and -40 mmHg LBNP) from resting baseline. Utilizing features extracted from common vital sign monitors, a classification accuracy of 82% and 91% was achieved for differentiating -30 and -40 mmHg LBNP, respectively from baseline. In chapter 4, cause-and-effect relationship between the representative signals of the cardiovascular and postural systems to ascertain blood pressure homeostasis during standing was performed. The degree of causal interaction between the two systems, studied via convergent cross mapping (CCM), showcased the existence of a significant bi-directional interaction between the representative signals of two systems to regulate blood pressure. Therefore, the two systems should be accounted for jointly when addressing physiology behind fall. Further, in chapter 5, the potential of artificial gravity (2-g) induced via short-arm human centrifuge at feet towards evoking blood pressure regulatory controls analogous to standing was investigated. The observation of no difference in the blood pressure regulatory controls, during 2-g centrifugation compared to standing, strongly supported the hypothesis of artificial hypergravity for mitigating cardiovascular deconditioning, hence minimizing post-flight orthostatic intolerance

Baroreflex Sensitivity Measured by Pulse Photoplethysmography

Novel methods for assessing baroreflex sensitivity (BRS) using only pulse photoplethysmography (PPG) signals are presented. Proposed methods were evaluated with a data set containing electrocardiogram (ECG), blood pressure (BP), and PPG signals from 17 healthy subjects during a tilt table test. The methods are based on a surrogate of α index, which is defined as the power ratio of RR interval variability (RRV) and that of systolic arterial pressure series variability (SAPV). The proposed α index surrogates use pulse-to-pulse interval series variability (PPV) as a surrogate of RRV, and different morphological features of the PPG pulse which have been hypothesized to be related to BP, as series surrogates of SAPV. A time-frequency technique was used to assess BRS, taking into account the non-stationarity of the protocol. This technique identifies two time-varying frequency bands where RRV and SAPV (or their surrogates) are expected to be coupled: the low frequency (LF, inside 0.04–0.15 Hz range), and the high frequency (HF, inside 0.15–0.4 Hz range) bands. Furthermore, time-frequency coherence is used to identify the time intervals when the RRV and SAPV (or their surrogates) are coupled. Conventional α index based on RRV and SAPV was used as Gold Standard. Spearman correlation coefficients between conventional α index and its PPG-based surrogates were computed and the paired Wilcoxon statistical test was applied in order to assess whether the indices can find significant differences (p < 0.05) between different stages of the protocol. The highest correlations with the conventional α index were obtained by the α-index-surrogate based on PPV and pulse up-slope (PUS), with 0.74 for LF band, and 0.81 for HF band. Furthermore, this index found significant differences between rest stages and tilt stage in both LF and HF bands according to the paired Wilcoxon test, as the conventional α index also did. These results suggest that BRS changes induced by the tilt test can be assessed with high correlation by only a PPG signal using PPV as RRV surrogate, and PPG morphological features as SAPV surrogates, being PUS the most convenient SAPV surrogate among the studied ones

Baroreflex Sensitivity Measured by Pulse Photoplethysmography

Novel methods for assessing baroreflex sensitivity (BRS) using only pulse photoplethysmography (PPG) signals are presented. Proposed methods were evaluated with a data set containing electrocardiogram (ECG), blood pressure (BP), and PPG signals from 17 healthy subjects during a tilt table test. The methods are based on a surrogate of α index, which is defined as the power ratio of RR interval variability (RRV) and that of systolic arterial pressure series variability (SAPV). The proposed α index surrogates use pulse-to-pulse interval series variability (PPV) as a surrogate of RRV, and different morphological features of the PPG pulse which have been hypothesized to be related to BP, as series surrogates of SAPV. A time-frequency technique was used to assess BRS, taking into account the non-stationarity of the protocol. This technique identifies two time-varying frequency bands where RRV and SAPV (or their surrogates) are expected to be coupled: the low frequency (LF, inside 0.04–0.15 Hz range), and the high frequency (HF, inside 0.15–0.4 Hz range) bands. Furthermore, time-frequency coherence is used to identify the time intervals when the RRV and SAPV (or their surrogates) are coupled. Conventional α index based on RRV and SAPV was used as Gold Standard. Spearman correlation coefficients between conventional α index and its PPG-based surrogates were computed and the paired Wilcoxon statistical test was applied in order to assess whether the indices can find significant differences (p &lt; 0.05) between different stages of the protocol. The highest correlations with the conventional α index were obtained by the α-index-surrogate based on PPV and pulse up-slope (PUS), with 0.74 for LF band, and 0.81 for HF band. Furthermore, this index found significant differences between rest stages and tilt stage in both LF and HF bands according to the paired Wilcoxon test, as the conventional α index also did. These results suggest that BRS changes induced by the tilt test can be assessed with high correlation by only a PPG signal using PPV as RRV surrogate, and PPG morphological features as SAPV surrogates, being PUS the most convenient SAPV surrogate among the studied ones

Theta-burst stimulation and frontotemporal regulation of cardiovascular autonomic outputs : the role of state anxiety

Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying top-down control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of top-down neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation

Advancing orthostatic hypotension diagnostics

This thesis investigated the diagnostics of orthostatic hypotension (OH). OH is defined as a sustained systolic/diastolic blood pressure (BP) drop larger than 20/10 mmHg within 3 minutes after standing up. OH is common among older adults aged above 65 years (6 – 31%) and geriatric outpatients (22-56%), sometimes accompanied by orthostatic intolerance (dizziness, light-headedness and blurry vision) and associated with poor clinical outcome (cardiovascular diseases, impaired cognitive performance and mortality). Current OH diagnostics is limited due to 1) contradictory evidence on the association between the OH definition and physical functioning and falls; 2) the uncertainty of the clinical value of continuous BP measurements, which may in contrast to intermittent sphygmomanometer measurements reflect the challenge posed to compensation systems and brain exposure to low perfusion pressures; and 3) the lack of assessment of systems compensating for orthostatic BP drops such as baroreflex sensitivity (i.e., heart rate increase in response to a BP drop to stabilize BP), peripheral vasoconstriction (i.e., narrowing of peripheral artery diameter in response to a BP drop to increase peripheral resistance and stabilize BP) and cerebral autoregulation (i.e., dilation of cerebral arterioles in response to a BP drop to keep cerebral blood flow constant). In conclusion, the currently used OH definition was found to be clinically valuable as patients diagnosed according to this definition are at increased risk of impaired physical functioning and falls. BP drop rate and BP recovery derived from continuous BP measurements were found to have added clinical value by their association with clinical outcome and may after confirmation of the results in further studies have to be incorporated in a new OH definition for continuous orthostatic BP measurements to better identify individuals with clinical consequences due to OH. Parameters expressing baroreflex sensitivity, cerebral oxygenation and cerebral autoregulation were by their sensitivity, test-retest reliability and validity in younger and older adults demonstrated to be potentially valuable, supporting further study on the clinical value of these parameters

Assessment and Mechanisms of Autonomic Function in Health and Disease

The autonomic nervous system is a master regulator of homeostasis, and the conviction that autonomic outflow is important on a patient-by-patient, minute-to-minute basis in both health and disease is the motivation for this thesis. The dissertation explores three aims that advance our understanding of the autonomic nervous system by elucidating the molecular mechanisms of autonomic regulation, validating widely used techniques for autonomic assessment, and developing and applying a new method to assess sympathetic vascular control. The first aim of the dissertation was to investigate the role of the Rho kinase pathway as a mediator of the autonomic effects of central angiotensin-II. This study was performed in conscious, chronically instrumented rabbits that received intracerebroventricular infusions of angiotensin-II, angiotensin-II with the specific Rho kinase inhibitor Fasudil, Fasudil alone, or a vehicle control over two weeks. Baseline hemodynamics were assessed daily, and cardiac and global vasomotor sympathetic tone was assessed by the hemodynamic response to autonomic blockers. Angiotensin-II raised blood pressure and cardiac and global vasomotor sympathetic outflow in a Rho-kinase dependent manner. In a separate cohort, renal sympathetic nerve activity was directly recorded and sympathetic baroreflex sensitivity was assessed, providing clear evidence that angiotensin-II increases renal sympathetic nerve activity and impairs baroreflex control thereof via a Rho kinase-dependent mechanism. In summary, the pressor, sympatho-excitatory, and baroreflex dysfunction caused by central angiotensin-II depend on Rho kinase activation. The second aim was to investigate the relationship between measures of pulse rate variability obtained by a chronically implanted arterial pressure telemeter with measures of heart rate variability derived by the standard electrocardiogram and the ability of pulse rate variability to reflect the autonomic contributions of heart rate variability. This study was conducted in conscious rabbits chronically instrumented with epicardial leads and arterial pressure telemeters. The autonomic contribution to pulse rate variability was assessed by pharmacological blockade, and the intrinsic variability of pulse rate was assessed by ventricular pacing. This study showed that pulse rate variability is a generally acceptable surrogate for heart rate variability for time- and frequency-domain measures, but the additional contribution of respiration to and the differing nonlinear properties of pulse rate variability should be considered by investigators. The third aim was to critically test the idea that the renal sympathetic nerves do not participate in the physiological control of renal blood flow. This study was conducted in conscious rabbits that underwent unilateral renal denervation and chronic instrumentation with arterial pressure telemeters and bilateral renal blood flow probes. Using time-varying transfer function analysis, this study showed active, rhythmic vasoconstriction of the renal vasculature with baroreflex properties in normally innervated kidneys, consistent with sympathetic vasomotion, which was absent in denervated kidneys. This refutes the long-held idea that sympathetic control of the renal vasculature is not physiological and has important applications to the burgeoning field of therapeutic renal denervation for cardiovascular disease

Cerebral blood flow links insulin resistance and baroreflex sensitivity

Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old) who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05). Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01). Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes. © 2013 Ryan et al

The Influence of Sex on the Relationship Between Arterial Mechanical Properties and Cardiovagal Baroreflex Sensitivity

Cardiovagal baroreflex sensitivity (cvBRS) demonstrates a strong relationship with arterial mechanical properties. Both cvBRS and arterial mechanics differ by sex such that males demonstrate greater cvBRS, yet lower large artery elasticity than females. Whether the relationship between cvBRS and arterial mechanics is similar in males and females remains unexamined. As a result, it is unclear whether arterial mechanics contribute to sex differences in cvBRS. This study investigated the cross-sectional relationship between cvBRS and arterial mechanical properties of the common carotid, carotid sinus and aortic arch (AA) in 36 (18 females) young, healthy normotensives. The cvBRS-arterial mechanics relationship did not reach statistical significance and did not differ by sex. Both cvBRS and AA distensibility were greater in females than males. Sex differences in cvBRS were eliminated after controlling for AA distensibility. These findings suggest that in this sample, AA elasticity may contribute to the greater cvBRS in females than males