Baroreflex Sensitivity Assessment Using the Sequence Method with Delayed Signals in End-Stage Renal Disease Patients.

Impaired baroreflex sensitivity (BRS) is partially responsible for erratic blood pressure fluctuations in End-Stage Renal Disease (ESRD) patients on chronic hemodialysis (HD), which is related to autonomic nervous dysfunction. The sequence method with delayed signals allows for the measurement of BRS in a non-invasive fashion and the investigation of alterations in this physiological feedback system that maintains BP within healthy limits. Our objective was to evaluate the modified delayed signals in the sequence method for BRS assessment in ESRD patients without pharmacological antihypertensive treatment and compare them with those of healthy subjects. We recruited 22 healthy volunteers and 18 patients with ESRD. We recorded continuous BP to obtain a 15-min time series of systolic blood pressure and interbeat intervals during the supine position (SP) and active standing (AS) position. The time series with delays from 0 to 5 heartbeats were used to calculate the BRS, number of data points, number of sequences, and estimation error. The BRS from the ESRD patients was smaller than in healthy subjects (p < 0.05). The BRS estimation with the delayed sequences also increased the number of data points and sequences and decreased the estimation error compared to the original time series. The modified sequence method with delayed signals may be useful for the measurement of baroreflex sensitivity in ESRD patients with a shorter recording time and maintaining an estimation error below 0.01 in both the supine and active standing positions. With this framework, it was corroborated that baroreflex sensitivity in ESRD is decreased when compared with healthy subjects.

Longitudinal Assessment of Autonomic Function during the Acute Phase of Spinal Cord Injury: Use of Low-Frequency Blood Pressure Variability as a Quantitative Measure of Autonomic Function.

High-level spinal cord injury (SCI) can disrupt cardiovascular autonomic function. However, the evolution of cardiovascular autonomic function in the acute phase following injury is unknown. We evaluated the timing, severity, progression, and implications of cardiovascular autonomic injury following acute SCI. We tested 63 individuals with acute traumatic SCI (aged 48 ± 2 years) at five time-points: <2 weeks, and 1, 3, 6-12, and >12 months post-injury. Supine beat-to-beat systolic arterial pressure (SAP) and R-R interval (RRI) were recorded and low-frequency variability (LF SAP and LF RRI) determined. Cross-spectral analyses were used to determine baroreflex function (low frequency) and cardiorespiratory interactions (high frequency). Known electrocardiographic (ECG) markers for arrhythmia and self-reported symptoms of cardiovascular dysfunction were determined. Comparisons were made with historical data from individuals with chronic SCI and able-bodied controls. Most individuals had high-level (74%) motor/sensory incomplete (63%) lesions. All participants had decreased LF SAP at <2 weeks (2.22 ± 0.65 mm Hg2). Autonomic injury was defined as high-level SCI with LF SAP <2 mm Hg2. Two distinct groups emerged by 1 month: autonomically complete SCI with sustained low LF SAP (0.76 ± 0.17 mm Hg2) and autonomically incomplete SCI with increased LF SAP (5.46 ± 1.0 mm Hg2, p < 0.05). Autonomically complete injuries did not recover over time. Cardiovascular symptoms were prevalent and worsened with time, especially in those with autonomically complete lesions, and chronic SCI. Baroreflex function and cardiorespiratory interactions were impaired after SCI. Risk of arrhythmia increased immediately after SCI, and remained elevated throughout the acute phase. Acute SCI is associated with severe cardiovascular dysfunction. LF SAP provides a simple, non-invasive, translatable, quantitative assessment of autonomic function, and is most informative 1 month after injury.

Assessment of baroreceptor reflex sensitivity in young obese Saudi males at rest and in response to physiological challenges.

Autonomic imbalance in overweight/obese persons could lead to an increased risk of cardiovascular complications including hypertension and arrhythmias. Baroreceptor reflex sensitivity is a sensitive indicator to detect an altered sympathovagal balance in overweight/obese individuals. This study investigated the effects of overweight/obesity on baroreceptor sensitivity in young Saudi males at rest and in response to physiological challenges. SUBJECTS AND METHODS: In this cross-sectional study, spontaneous baroreceptor sensitivity at rest and in response to deep breathing, isometric hand grip exercise and moderate intensity isotonic exercise were recorded in 20 normal weight and 20 overweight/obese subjects. Finger arterial blood pressure signal, recorded through Finometer, was used to calculate baroreceptor sensitivity through cross-correlation method. The baroreceptor sensitivity data were log transformed before application of parametric tests. RESULTS: The spontaneous baroreceptor sensitivity was similar in both groups at baseline, but exhibited a significant increase during deep breathing only in normal weight (p < .001). Immediately after the isotonic exercise the baroreceptor sensitivity was significantly lower than baseline in both normal weight and overweight/obese and remained significantly lower in overweight/obese individuals compared to normal weight (p < .05) throughout the recovery period. There was a significant rise in baroreceptor sensitivity after isometric exercise in overweight/obese group only (p = .001). Pearson's correlation showed a significant negative correlation of baroreceptor sensitivity with body mass index during deep breathing (r = -.472, p = .004) and in post-isotonic exercise recovery period (r = -.414, p = .013). CONCLUSION: A significantly reduced baroreceptor sensitivity response to deep breathing, reduced baroreceptor sensitivity recovery after isotonic exercise, and an exaggerated shoot up after isometric exercise in overweight/obese suggests an altered sympathovagal balance. Baroreceptor sensitivity measurements in response to physiological challenges, deep breathing, and isotonic exercise, may be more sensitive investigations for detection of early attenuation of cardiac autonomic function. This would enable timely intervention thereby delaying complications and improving the quality of life.

Assessment of arterial baroreflex sensitivity by different computational analyses of pressure wave signals alone.

BACKGROUND AND OBJECTIVE: Baroreflex sensitivity (BRS) is an important indicator of the functionality of the arterial baroreceptors, and its assessment may have major research and clinical implications. An important requirement for its quantification is the continuous recording of electrocardiography (ECG) signal, so as to extract the RR interval, in parallel with continuous beat-to-beat blood pressure recording. We aimed to accurately calculate the RR Interval from pressure wave recordings per se, namely, the Pulse Interval (PI) using various arterial pulse wave analysis algorithms and to evaluate the precision and accuracy of BRS values calculated with the PI compared to BRS values calculated with the RR Interval. METHODS: We analyzed the open access data of the Eurobavar study, which contains a set of ECG and arterial blood pressure (BP) wave signals recorded at 11 European centers. Pressure waveforms were continuously recorded by the Finapres apparatus which uses a finger cuff. The cuff pressure around the finger is dynamically adjusted by a servo-system to equal intra-arterial pressure, thus allowing the continuous recording of beat-to-beat BP waves. RR Interval was calculated from the ECG, whereas, PI was extracted from the arterial pulse waveforms, using 4 different methods (minimum, maximum, maximum 1st derivative and intersecting tangents method). BRS values were estimated by time domain and frequency domain methods. In order to compare agreement, accuracy, precision, variability, and the association between the reference BRS using the RR Interval and the BRS values using PI, standard statistical methods (i.e. intraclass correlation coefficients, RMSE, regression analysis) and Bland-Altman methods were performed. RESULTS: We found that analysis of pressure waves alone by frequency-based (i.e. spectral) methods, provides the most accurate results of BRS estimation compared to time-domain methods (ICC > 0.9, R > 0.9, RMSE > 0.8 ms/mmHg). Concerning the spectral method, any algorithm for PI calculation is sufficient, as all show excellent agreement with the respective RR-intervals determined by ECG time series. Only the intersecting tangents and the maximum 1st derivative methods for PI calculation produce the most accurate results in time domain BRS estimation. CONCLUSION: BRS estimation by proper analysis of pressure wave signals alone is feasible and accurate. Further studies are needed to investigate the clinical validity and relevance of the different BRS estimations in diagnostic, prognostic and therapeutic levels.

Assessment of baroreflex sensitivity has no prognostic value in contemporary, optimally managed patients with mild-to-moderate heart failure with reduced ejection fraction: a retrospective analysis of 5-year survival.

OBJECTIVES: We evaluated the prognostic value of cardiac baroreflex sensitivity (BRS) in contemporary, optimally treated patients with mild-to-moderate heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Data from 97 patients with HFrEF (left ventricular ejection fraction 32 ± 6%, all receiving angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, 85% receiving aldosterone antagonist) were analysed retrospectively. All patients underwent standard clinical assessment, cardiopulmonary exercise testing and BRS evaluation with three methods: the phenylephrine (BRS-Phe), the sequence (BRS-Seq) and the controlled breathing (BRS-CtrBr) method. Data on 5-year all-cause mortality and appropriate and documented implantable cardioverter-defibrillator (ICD) discharges were collected. During a mean follow-up of 53 ± 15 months, the composite endpoint of all-cause death and appropriate and documented ICD discharge occurred in 31 (32%) patients. BRS measures assessed using all three methods were not related to survival in univariate Cox proportional hazards analyses (all P >0.25). There were also no differences in survival between low vs. preserved BRS groups, irrespective of the method used for BRS assessment (all P ≥0.15). BRS-Phe correlated with several clinically important variables (including left ventricular ejection fraction: rS = 0.27, and peak oxygen consumption: rS = 0.32, both P < 0.05), while clinical associations of BRS-Seq and BRS-CtrBr were sparse. CONCLUSIONS: Assessment of cardiac BRS provides no prognostic information in the contemporary mild-to-moderate HFrEF population receiving optimal management.

First granted example of novel FDA trial design under Expedited Access Pathway for premarket approval: BeAT-HF.

BACKGROUND: The Food and Drug Administration (FDA) initiated the Expedited Access Pathway (EAP) to accelerate approval of novel therapies targeting unmet needs for life-threatening conditions. EAP allows for the possibility of initial FDA approval using intermediate end points with postapproval demonstration of improved outcomes. OBJECTIVE: Describe the EAP process using the BeAT-HF trial as a case study. METHODS: BeAT-HF will examine the safety and effectiveness of baroreflex activation therapy (BAT) in heart failure patients with reduced ejection fraction using an Expedited and Extended Phase design. In the Expedited Phase, BAT plus guideline-directed medical therapy (GDMT) will be compared at 6 months postimplant to GDMT alone using 3 intermediate end points: 6-minute hall walk distance, Minnesota Living with Heart Failure Questionnaire, and N-terminal pro-B-type natriuretic peptide. The rate of heart failure morbidity and cardiovascular mortality will be compared between the arms to evaluate early trending using predictive probability modeling. Sample size of 264 patients randomized 1:1 to BAT + GDMT versus GDMT alone provides 81% power for the Expedited Phase intermediate end points. For the Extended Phase, the heart failure morbidity and cardiovascular mortality end point is based on an expected event rate of 0.4 events/patient/year in the GDMT arm. With an adaptive sample size selection design for robustness to inaccurate assumptions, a sample size of 480-960 randomized patients followed ≥2 years allows detecting a 30% reduction in the primary end point with a power of 97.5%. CONCLUSION: Through a unique collaboration with FDA under the EAP, the BeAT-HF trial design allows for the possibility of approval of BAT, initially for symptom relief and subsequently for outcomes improvement.

Noninvasive assessment of autonomic function in human neonates born at the extremes of fetal growth spectrum.

Birth weight is associated with adult cardiovascular disease, such that those at both ends of the spectrum are at increased risk. This may be driven in part by modification to autonomic control, a mechanistic contributor to hypertension. However, birth weight is a relatively crude surrogate of fetal growth; and newborn body composition may more accurately identify the "at risk" infant. Accordingly, we sought to determine whether newborns with high or low body fat have altered autonomic control of vasomotor function and cardiac contractility. Body fat was assessed by air-displacement plethysmography <24 h postnatal. Measures of spontaneous baroreflex sensitivity (sBRS), blood pressure variability (BPV), and dP/dtmax variability were compared between newborns categorized according to established body fat percentiles: high body fat (HBF, >90th percentile, n = 7), low body fat (LBF, ≤10th percentile, n = 12), and normal body fat (control, >25th to ≤75th percentile, n = 23). BPV was similar across body fat percentiles; similarly, low frequency dP/dtmax variability was similar across body fat percentiles. sBRS was reduced in HBF compared to controls (11.0 ± 6.0 vs. 20.1 ± 9.4 msec/mmHg, P = 0.03), but LBF did not differ (18.4 ± 6.0 msec/mmHg, P = 0.80). Across the entire body fat spectrum (n = 62), there was a nonlinear association between newborn body fat and sBRS (P = 0.03) that was independent of birth weight (P = 0.04). Autonomic modulation of vasomotor function and cardiac contractility in the newborn did not differ by body fat, but newborns born with high body fat show depressed baroreflex sensitivity.

Assessment of sympathetic neural activity in chronic insomnia: evidence for elevated cardiovascular risk.

Study Objectives: Chronic insomnia affects up to 15 per cent of adults. Recent cross-sectional and prospective epidemiological studies report an association between insomnia and hypertension, including incident hypertension, yet mechanisms underlying the association remain unknown. We hypothesized that participants with chronic insomnia would have elevated sympathetic neural outflow, blunted baroreflex sensitivity, and augmented sympathetic neural and cardiovascular reactivity to stress when compared with good-sleeper controls. Methods: Twelve participants with chronic insomnia (11 women, 1 man) and 12 controls (8 women, 4 men) underwent one night of laboratory polysomnography, two weeks of at-home wrist actigraphy, and one night of controlled laboratory sleep prior to a comprehensive morning autonomic function test. The autonomic function test consisted of simultaneous recordings of muscle sympathetic nerve activity (MSNA; microneurography), beat-to-beat blood pressure (finger plethysmography), and heart rate (electrocardiogram) during a 10 min supine baseline and a 2 min cold pressor test. Results: Baseline blood pressure, heart rate, and MSNA were not different between groups, but sympathetic baroreflex sensitivity was significantly blunted in participants with insomnia (-2.1 ± 1.0 vs. -4.3 ± 1.3 bursts/100 heartbeats/mm Hg; p < 0.001). During the cold pressor test, systolic arterial pressure reactivity (Δ21 ± 11 vs. Δ14 ± 8 mm Hg; time × group = 0.04) and total MSNA reactivity (Δ127%, 54%-208% vs. Δ52%, 30%-81%; time × group = 0.02) were augmented in chronic insomnia. Conclusions: Participants with chronic insomnia demonstrated impaired sympathetic baroreflex function and augmented neural cardiovascular responsiveness to stress, when compared with controls. These findings support growing evidence of cardiovascular risk and physiological hyperarousal in chronic insomnia. Clinical Trial Registration: NCT02048878. https://clinicaltrials.gov/ct2/show/NCT02048878.

A method for assessment of the dynamic response of the arterial baroreflex.

AIM: The baroreflex is a key mechanism in cardiovascular regulation, and alterations in baroreceptor function are seen in many diseases, including heart failure, obesity and hypertension. We propose a new method for analysing baroreceptor function from continuous blood pressure (BP) and heart rate (HR) in both health and disease. METHODS: Forty-eight-hour data series of BP and HR were collected with telemetry. Sprague Dawley rats on standard chow (n = 11) served as controls, while rats on a high-fat, high-fructose (HFHC) diet (n = 6) constituted the obese-hypertensive model. A third group of rats underwent autonomic blockade (n = 6). An autoregressive-moving-average with exogenous inputs (ARMAX) model was applied to the data and compared with the α-coefficient. RESULTS: Autonomic blockade caused a significant reduction in the strength of the baroreflex as estimated by ARMAX [ARMAX- baroreflex sensitivity (BRS)] -0.03 ± 0.01 vs. -0.19 ± 0.04 bpm heartbeat-1) . Both methods showed a ~50% reduction in BRS in the obese-hypertensive group compared with control (body weight 531 ± 27 vs. 458 ± 19 g, P < 0.05; mean arterial pressure 119 ± 3 vs. 102 ± 1 mmHg, P < 0.05; ARMAX-BRS -0.08 ± 0.01 vs. -0.15 ± 0.01 bpm heartbeat-1 , P < 0.05; α-coefficient BRS 0.51 ± 0.07 vs. 0.89 ± 0.07 ms mmHg-1 , P < 0.05). The ARMAX method additionally showed the open-loop gain of the baroreflex to be reduced by ~50% in the obese-hypertensive group (-2.3 ± 0.3 vs. -4.1 ± 0.3 bpm, P < 0.05), while the rate constant was similar between groups. CONCLUSION: The ARMAX model represents an efficient method for estimating several aspects of the baroreflex. The open-loop gain of the baroreflex was attenuated in obese-hypertensive rats compared with control, while the time response was similar. The algorithm can be applied to other species including humans.

Non-invasive approach for the assessment of sympathetic baroreflex function: A feasibility study.

BACKGROUND: Evaluation of sympathetic baroreflex (sBR) function in humans requires intra-neural recording of muscle sympathetic nerve activity (MSNA) by microneurography. AIMS: We proposed noninvasive approach for the evaluation of sBR function by applying the threshold-analysis (traditionally, based on MSNA) to systemic vascular resistance (SVR) measurement by photoplethysmography. METHODS & RESULTS: In nine healthy subjects (5M; age: 25±5y), the threshold-analysis was calculated twice: using MSNA and SVR. Both methods yield comparable results in men (T50(burst-vs.-svr): CV=8.8%, r>0.9; Slope(burst-svr): CV=30.1%; r>0.9), but not in women. CONCLUSIONS: SVR-based threshold-analysis is feasible in healthy young subjects and provides a promising alternative to the traditional MSNA-based approach.

[Resistant hypertension and carotid baroreceptors stimulation]. / HTA résistante et barostimulation carotidienne.

Resistant hypertension remains a frequent and difficult situation; its management has been recently clarified by guidelines from the French Society of Hypertension. Baroreceptor stimulation (BAROSTIM) is an emerging technique aimed at decreasing blood pressure in resistant hypertension. BAROSTIM interferes with baroreflex loop by stimulating baroreceptors and afferences of the baroreflex. There is only one randomized control trial with this technique which showed a modest but apparently durable blood pressure reduction. More evidences are required to refine the place of BAROSTIM, particularly with new devices. Together with renal denervation, BAROSTIM belongs to a new family of interventional techniques which should be considered as potential add-on therapies while optimal medical therapy remains the cornerstone of hypertension management.

Chronotropic Incompetence During Exercise in Type 2 Diabetes: Aetiology, Assessment Methodology, Prognostic Impact and Therapy.

During incremental exercise tests, chronotropic incompetence (CI), which is the inability of the heart rate (HR) to rise in proportion to an increase in metabolic demand, is often observed in patients with type 2 diabetes mellitus (T2DM). Despite the fact that CI is associated with exercise intolerance and elevated risks of development of cardiovascular disease and premature death, this clinical anomaly is often ignored or overlooked by clinicians and physiologists. CI is, however, a significant clinical abnormality that deserves further attention, examination and treatment. The aetiology of CI in T2DM remains poorly understood and is complex. Certain T2DM-related co-morbidities or physiological anomalies may contribute to development of CI, such as altered blood catecholamine and/or potassium levels during exercise, structural myocardial abnormalities, ventricular and/or arterial stiffness, impaired baroreflex sensitivity and cardiovascular autonomic neuropathy. Clinicians should thus be aware of the potential presence of yet undetected anomalies or diseases in T2DM patients who experience CI during exercise testing. However, an effective treatment for CI in T2DM is yet to be developed. Exercise training programmes seem to be the only potentially effective and feasible interventions for partial restoration of the chronotropic response in T2DM, but it remains poorly understood how these interventions lead to restoration of the chronotropic response. Studies are thus warranted to elucidate the aetiology of CI and develop an effective treatment for CI in T2DM. In particular, the impact of (different) exercise interventions on CI in T2DM deserves greater attention in future studies.

Assessment of baroreflex sensitivity from spontaneous oscillations of blood pressure and heart rate: proven clinical value?

The baroreceptor-heart rate reflex (baroreflex sensitivity, BRS) is a key mechanism contributing to the neural regulation of the cardiovascular system. Several methods have been proposed so far to assess BRS by analyzing the spontaneous beat-to-beat fluctuations of arterial blood pressure and heart rate. These methods are inherently simple, non-invasive and low-cost. This study is an attempt to address the question of whether spontaneous baroreflex methods have proven to be of value in the clinical setting. In the first part of this article, we critically review most representative clinical studies using spontaneous BRS techniques either for risk stratification or treatment evaluation, these being major issues in the clinical management of the patients. In the second part, we address two important aspects of spontaneous BRS measurements: measurability and reliability. Estimation of BRS in the studies selected for the review was performed according to the sequence, transfer function, alpha-index and phase-rectified signal averaging method. Arterial blood pressure was recorded non-invasively during supine, short-term (<30 min) laboratory recordings. The conclusion from this review is that spontaneous BRS techniques have been shown to be of great value in clinical practice but further work is needed to confirm the validity of previous findings and to widen the field of clinical applications. Measurability and reliability can be a major issue in the measurement of spontaneous BRS, particularly in some patient populations like post-myocardial infarction and heart failure patents. Main causes of poor measurability are: non-sinus rhythm, a high rate of ectopic beats and the need for recorded time series of RR interval and arterial blood pressure to satisfy the constraints of the different BRS estimation algorithms. As for reliability, within-subject variability is rather high in the measurements of spontaneous BRS and, therefore, should be carefully taken into account when BRS measurements are used to detect treatment effects in individual patients.

Finger volume pulse waveforms facilitate reliable assessment of heart rate variability, but not blood pressure variability or baroreflex function.

BACKGROUND: We sought to determine whether heart rate variability (HRV), blood pressure (BP) variability, and baroreceptor-heart rate reflex sensitivity can be reliably assessed using finger volume pulse waveforms obtained from the commercially available EndoPAT device. METHODS: Non-invasive BP (Finometer Pro as a non-invasive standard) and finger volume (EndoPAT) waveforms were recorded in 65 adults (37 ± 14 years; 60% female) and systolic BP and heart rate (HR) time series were derived after calibrating the EndoPAT signal based on systolic and diastolic BP values obtained by a sphygomomanometer. Transfer function analyses were performed to test for coherence between systolic BP and HR time series derived from the Finometer and EndoPAT devices. Time-domain HRV parameters, frequency domain HR and systolic BP variability parameters, and baroreflex sensitivity (sequence technique) were computed from Finometer- and EndoPAT-derived time series and intraclass correlation coefficients (ICC) were calculated. RESULTS: Squared coherence between systolic BP time series derived from the Finometer and EndoPAT devices was low, suggesting poor correlation. In contrast, squared coherence between HR time series derived from the two devices was excellent [High Frequency (HF) = 0.80, Low Frequency (LF) = 0.81], with gain values close to 1.0. ICC values for time- and frequency-domain HRV parameters were excellent (>0.9 except for relative HF HRV, which was 0.77), while ICC values for frequency-domain BP variability parameters and baroreceptor-HR reflex sensitivity were low. CONCLUSIONS: Finger volume pulse waveforms can be used to reliably assess both time-domain and frequency-domain HR variability. However, frequency domain BP variability parameters cannot be reliably assessed from finger volume pulse waveforms using the simple calibration technique used in this study.

The repeated sit-to-stand maneuver is a superior method for cardiac baroreflex assessment: a comparison with the modified Oxford method and Valsalva maneuver.

Baroreflex assessment has diagnostic and prognostic utility in the clinical and research environments, and there is a need for a reliable, simple, noninvasive method of assessment. The repeated sit-to-stand method induces oscillatory changes in blood pressure (BP) at a desired frequency and is suitable for assessing dynamic baroreflex sensitivity (BRS). However, little is known about the reliability of this method and its ability to discern fundamental properties of the baroreflex. In this study we sought to: 1) evaluate the reliability of the sit-to-stand method for assessing BRS and compare its performance against two established methods (Oxford method and Valsalva maneuver), and 2) examine whether the frequency of the sit-to-stand method influences hysteresis. Sixteen healthy participants underwent three trials of each method. For the sit-to-stand method, which was performed at 0.1 and 0.05 Hz, BRS was quantified as an integrated response (BRSINT) and in response to falling and rising BP (BRSDOWN and BRSUP, respectively). Test retest reliability was assessed using the intraclass correlation coefficient (ICC). Irrespective of frequency, the ICC for BRSINT during the sit-to-stand method was ≥0.88. The ICC for a rising BP evoked by phenylephrine (PEGAIN) in the Oxford method was 0.78 and ≤0.5 for the remaining measures. During the sit-to-stand method, hysteresis was apparent in all participants at 0.1 Hz but was absent at 0.05 Hz. These findings indicate the sit-to-stand method is a statistically reliable BRS assessment tool and suitable for the examination of baroreflex hysteresis. Using this approach we showed that baroreflex hysteresis is a frequency-dependent phenomenon.

Assessment of human baroreflex function using carotid ultrasonography: what have we learnt?

The arterial baroreflex is critical to both short- and long-term regulation of blood pressure. However, human baroreflex research has been largely limited to the association between blood pressure and cardiac period (or heart rate) or indices of vascular sympathetic function. Over the past decade, emerging techniques based on carotid ultrasound imaging have allowed new means of understanding and measuring the baroreflex. In this review, we describe the assessment of the mechanical and neural components of the baroreflex through the use of carotid ultrasound imaging. The mechanical component refers to the change in carotid artery diameter in response to changes in arterial pressure, and the neural component refers to the change in R-R interval (cardiac baroreflex) or muscle sympathetic nerve activity (sympathetic baroreflex) in response to this barosensory vessel stretch. The key analytical concepts and techniques are discussed, with a focus on the assessment of baroreflex sensitivity via the modified Oxford method. We illustrate how the application of carotid ultrasound imaging has contributed to a greater understanding of baroreflex physiology in humans, covering topics such as ageing and diurnal variation, and physiological challenges including exercise, postural changes and mental stress.

Assessment of the vasodepressor reflex in carotid sinus syndrome.

BACKGROUND: Assessment of the vasodepressor reflex in carotid sinus syndrome is influenced by the method of execution of the carotid sinus massage and the coexistence of the cardioinhibitory reflex. METHODS AND RESULTS: Carotid sinus massage reproduced spontaneous symptoms in 164 patients in the presence of hypotension or bradycardia (method of symptoms). When an asystolic pause was induced, the vasodepressor reflex was reassessed after suppression of the asystolic reflex by means of 0.02 mg/kg IV atropine. An isolated vasodepressor form was found in 32 (20%) patients, who had lowest systolic blood pressure (SBP) of 65±15 mm Hg. Of these, only 21 (66%) patients had an SBP fall ≥50 mm Hg, which is the universally accepted cut-off value for the diagnosis of the vasodepressor form. Conversely, a lowest SBP value of ≤85 mm Hg (corresponding to the fifth percentile) detected 97% of vasodepressor patients, but was also present in 84% of the 132 patients with an asystolic reflex. These latter patients had both asystole ≥3 s (mean 7.6±2.2 s) and SBP fall to 63±22 mm Hg: in 46 (28%) patients, symptoms persisted after atropine (mixed form), in the remaining 86 (52%) patients, symptoms did not (cardioinhibitory form) persist. CONCLUSIONS: The current definition of ≥50 mm Hg SBP fall failed to identify one third of patients with isolated vasodepressor form. A cut-off value of symptomatic SBP of ≤85 mm Hg seems more appropriate, but it is unable to identify cardioinhibitory forms. In asystolic forms, atropine testing is able to distinguish a cardioinhibitory form from a mixed form.

Assessment of baroreflex sensitivity by continuous noninvasive monitoring of peripheral and central aortic pressure.

Noninvasive assessment of baroreceptor sensitivity (BRS) facilitates clinical investigation of autonomic function. The spontaneous sequence method estimates BRS using the continuous measurement of arterial pressure in the finger. Since the baroreceptors are centrally located (aortic arch, carotid arteries), this study assessed the use of a continuous aortic pressure signal derived from the peripheral pressure pulse to compute the BRS from changes in systolic pressure (SBP) and pulse interval (PI). BRS computed from central aortic (cBRS) and peripheral pressure (pBRS) was calculated in 12 healthy subjects (25-62 years, 7 females). The difference between pBRS and cBRS was calculated for four levels of pulse lags between changes in SBP and PI. For each lag and for the pooled data for all lags, cBRS was significantly correlated with pBRS (r(2)=0.82). The within subject difference ranged from -41.2% to 59.2%. This difference was not related to age, gender of hemodynamic parameters (systolic or diastolic pressure, heart rate, aortic pulse wave velocity). However 18.2% of the variance was due to the difference in the number of spontaneous pulse sequences used to determine values of cBRS and pBRS. The differences between pBRS and cBRS are in the range of values of BRS as those found, in other studies, to discriminate between patient groups with different levels of autonomic function. Findings of this study suggest that, given the heart rate dependent amplification of the arterial pressure pulse between the central aorta and the peripheral limbs, BRS determined from central aortic pressure derived from the peripheral pulse may provide an improved method for noninvasive assessment of baroreceptor function.

[Arterial baroreflex--physiological role and assessment of functioning]. / Odruch z baroreceptorów tetniczych--znaczenie fizjologiczne i ocena funkcjonowania.

Arterial baroreflex is one of the key mechanisms responsible for the homeostasis maintenance within the cardiovascular system. Through the modulation of sympathetic and parasympathetic drive within the autonomic nervous system, baroreflex enables to stabilize arterial blood pressure and maintain perfusion within critical organs (e.g. brain, heart). This review provides the physiological background of the baroreflex functioning and describes the methodology for assessing the arterial baroreflex sensitivity (BRS). Decreased BRS reflects autonomic imbalance and predicts unfavorable outcome in cardiovascular diseases accompanied by the autonomic dysfunction, such as arterial hypertension and heart failure. BRS assessment methods can be divided into those that are performed in resting conditions (the measurements of spontaneous BRS, e.g. the sequence or spectral analysis method) and methods with the application of the external stimuli, which may be either non-invasive (e.g. the controlled breathing method) or invasive (e.g. the phenylephrine method).