Lippincott Williams & Wilkins
SUPPLEMENTAL MATERIALBaroreceptor Reflex Function: Impact on Perioperative Outcomes and Chronic Pain Heberto Suarez-Roca, MD, PhD1, Rebecca Y. Klinger, MD, MS2, Mihai V. Podgoreanu, MD2, Ru-Rong Ji, PhD1, Martin I. Sigurdsson, MD, PhD2, Nathan Waldron, MD2, Joseph P. Mathew, MD, MHSc, MBA2, and William Maixner, DDS, PhD11 Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, NC2 Division of Cardiothoracic Anesthesia and Critical Care Medicine, Department of Anesthesiology, Duke University, Durham, NCMeasurement of baroreflex sensitivityOne way of assessing baroreceptor function is through the measurement of baroreceptor sensitivity (BRS). BRS is typically defined by the relationship between the change in arterial pressure (AP) and the associated effect on the inter-beat interval.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYXJhdGk8L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFyPjxS
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYXJhdGk8L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 1,2 Most procedures used to evaluate BRS measure the relationship between the change in heart rate, estimated by the R-R interval (RRI) in the electrocardiogram (ECG), as a function of the change in systolic AP (SAP). The gold-standard procedure for assessing BRS is to measure the ratio of change in heart rate to the change in SAP in responses to the intravenous administration of a low dose of a vasopressor agent (e.g., phenylephrine).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbXl0aDwvQXV0aG9yPjxZZWFyPjE5Njk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 7 Techniques used to evaluate cardiopulmonary baroreflexes include measuring heart rate and blood pressure responses to lower body negative or positive pressure, extremity congesting cuffs, controlled hemorrhage, leg elevation, upright tilting, administration of a vasodilator (e.g., nitroglycerine), deep breathing, hand grip stress, and the Valsalva maneuver as reviewed elsewhere. ADDIN EN.CITE <EndNote><Cite><Author>Mark</Author><Year>2011</Year><RecNum>966</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>966</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485179368">966</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mark, A. L.</author><author>Mancia, G.</author></authors></contributors><titles><title>Cardiopulmonary baroreflexes in humans</title><secondary-title>Compr Physiol</secondary-title></titles><periodical><full-title>Compr Physiol</full-title></periodical><pages>795-813</pages><volume>Supl 8</volume><dates><year>2011</year></dates><urls><related-urls><url> Given the evidence that baroreceptors are not only activated by acute changes in arterial pressure but also in response to small natural continuous variations in blood pressure, non-invasive methods have been developed that assess BRS using the spontaneous covariation of heart rate and blood pressure (called ‘spontaneous BRS’).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdXNjaGVrPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA 6,10-18 Current methods estimate BRS using either time- or frequency-domain analyses, which attempt to account for the complex physiology of baroreflex regulation, separation of baroreflex signals from background noise under a variety of physiological and pathological conditions have been developed. PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb2JiZTwvQXV0aG9yPjxZZWFyPjE5ODc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 7,14,19-30 In this regard, a delay of usually 1 to 4 beats (or up to 2000-3000 ms) is usually applied to SAP with respect to RRI to obtain the best regression line fit between the SAP and RRI values resulting in a more accurate BRS value, especially at a mean RRI < 800 ms, (i.e., heart rate > 75 bpm).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJ0aW5lei1HYXJjaWE8L0F1dGhvcj48WWVhcj4yMDEy
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ADDIN EN.CITE.DATA 34-36 Dynamically assessing or controlling respiratory rate is important, as it influences high frequency oscillations. To assure that the oscillations in the RRI and SAP signals are coherent (i.e., synchronized or correlated with each other), spectral densities obtained from frequency-domain analyses can be integrated over the segment of the low frequency band (LF; 0.04 -0.15 Hz) that exceeds the selected level of coherence (usually 0.5) to exclude oscillations that are not synchronized.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5kZSBCb2VyPC9BdXRob3I+PFllYXI+MTk4NTwvWWVhcj48
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ADDIN EN.CITE.DATA 4,14,19,37-39 In addition, to ascertaining that SAP and RRI coherent oscillations have an appropriate phase relationship, spectral density is integrated over the segment of the LF band where the phase difference is negative (i.e., SAP changes preceded those expected in the RRI). ADDIN EN.CITE <EndNote><Cite><Author>Kuusela</Author><Year>2012</Year><RecNum>2464</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>2464</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1509044097">2464</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Kuusela, T.A.</author></authors><secondary-authors><author>Kamath, M.; Watanabe, M.; Upton A.</author></secondary-authors></contributors><titles><title>Methodological Aspects of Baroreflex Sensitivity Analysis</title><secondary-title>Heart Rate Variability (HRV) Signal Analysis: Clinical Applications
</secondary-title></titles><pages>43–58</pages><section>3</section><dates><year>2012</year></dates><publisher>CRC Press </publisher><isbn>Print ISBN: 978-1-4398-4980-4
eBook ISBN: 978-1-4665-7605-6</isbn><urls></urls><electronic-resource-num>10.1201/b12756-5</electronic-resource-num></record></Cite></EndNote>4 Since a phase difference defines only the relationship between the two signals but not which signal leads to the other (i.e., cause-effect relation between SAP and RRI oscillations), the linear modeling of the SAP as the input signal and the RRI as the output has been developed using different algorithms, such as a transfer function.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QaW5uYTwvQXV0aG9yPjxZZWFyPjIwMDI8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 24,25 Table 1S shows the advantages and limitations of each method. While the results of computing BRS based on either time or frequency domain are not directly comparable to each other a combination of methods should be considered when studying the relationship between BRS and autonomic function. Figure 1S shows the estimation of BRS using the time-domain based sequence method. BRS thresholds for defining normal and abnormal BRS have been proposed by the Autonomic Tone and Reflexes After Myocardial Infarction Study.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYSBSb3ZlcmU8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFy
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ADDIN EN.CITE.DATA 7,40 In general, normal BRS is defined as > 6 ms/mmHg. BRS dysfunction can be classified as moderate (3-6 ms/mmHg) and severe (< 3 ms/mmHg). A recent study of patients with chronic obstructive pulmonary disease verified that the healthy volunteer cohort (average age 67 years) had a spontaneous BRS value of 7.8 ± 4.9 ms/mmHg. ADDIN EN.CITE <EndNote><Cite><Author>Costes</Author><Year>2004</Year><RecNum>752</RecNum><DisplayText><style face="superscript">41</style></DisplayText><record><rec-number>752</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485179089">752</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Costes, F.</author><author>Roche, F.</author><author>Pichot, V.</author><author>Vergnon, J. M.</author><author>Garet, M.</author><author>Barthelemy, J. C.</author></authors></contributors><auth-address>Cardiorespiratory Function Test Laboratory-GIP Exercice, and Dept of Pneumology and Thoracic Oncology, University Hospital, Saint-Etienne, France. frederic.costes@chu-st-etienne.fr</auth-address><titles><title>Influence of exercise training on cardiac baroreflex sensitivity in patients with COPD</title><secondary-title>Eur Respir J</secondary-title></titles><periodical><full-title>Eur Respir J</full-title></periodical><pages>396-401</pages><volume>23</volume><number>3</number><keywords><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/physiology</keyword><keyword>Case-Control Studies</keyword><keyword>*Exercise</keyword><keyword>Exercise Test</keyword><keyword>Exercise Therapy</keyword><keyword>Exercise Tolerance</keyword><keyword>Heart/*innervation</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Physical Endurance</keyword><keyword>Pulmonary Disease, Chronic Obstructive/physiopathology/*rehabilitation</keyword><keyword>Respiratory Function Tests</keyword><keyword>Tilt-Table Test</keyword></keywords><dates><year>2004</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0903-1936 (Print)
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ADDIN EN.CITE.DATA 42While a recent critical appraisal of the reliability and clinical relevance of spontaneous BRS measurement indicates that it is generally a powerful tool for both prognostication of cardiovascular disease and treatment evaluation for both cardiovascular and non-cardiovascular diseases, several methodologic issues can hamper the reliable measurement of BRS. ADDIN EN.CITE <EndNote><Cite><Author>Pinna</Author><Year>2015</Year><RecNum>135</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>135</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485177972">135</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pinna, G. D.</author><author>Maestri, R.</author><author>La Rovere, M. T.</author></authors></contributors><auth-address>Department of Biomedical Engineering, Fondazione S. Maugeri-IRCCS, Montescano, Italy.</auth-address><titles><title>Assessment of baroreflex sensitivity from spontaneous oscillations of blood pressure and heart rate: proven clinical value?</title><secondary-title>Physiol Meas</secondary-title></titles><periodical><full-title>Physiol Meas</full-title></periodical><pages>741-53</pages><volume>36</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Arterial Pressure/*physiology</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure Determination/*methods</keyword><keyword>Electrocardiography/*methods</keyword><keyword>Heart Diseases/diagnosis/physiopathology</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Humans</keyword><keyword>Reproducibility of Results</keyword><keyword>Signal Processing, Computer-Assisted</keyword></keywords><dates><year>2015</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1361-6579 (Electronic)
0967-3334 (Linking)</isbn><accession-num>25798657</accession-num><urls><related-urls><url> Factors affecting the evaluation of spontaneous BRS include non-sinus rhythm, significant ectopy, and the requirement of recorded time series of R-R interval and arterial blood pressure to satisfy BRS estimation algorithms. ADDIN EN.CITE <EndNote><Cite><Author>Pinna</Author><Year>2015</Year><RecNum>135</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>135</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485177972">135</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pinna, G. D.</author><author>Maestri, R.</author><author>La Rovere, M. T.</author></authors></contributors><auth-address>Department of Biomedical Engineering, Fondazione S. Maugeri-IRCCS, Montescano, Italy.</auth-address><titles><title>Assessment of baroreflex sensitivity from spontaneous oscillations of blood pressure and heart rate: proven clinical value?</title><secondary-title>Physiol Meas</secondary-title></titles><periodical><full-title>Physiol Meas</full-title></periodical><pages>741-53</pages><volume>36</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Arterial Pressure/*physiology</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure Determination/*methods</keyword><keyword>Electrocardiography/*methods</keyword><keyword>Heart Diseases/diagnosis/physiopathology</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Humans</keyword><keyword>Reproducibility of Results</keyword><keyword>Signal Processing, Computer-Assisted</keyword></keywords><dates><year>2015</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1361-6579 (Electronic)
0967-3334 (Linking)</isbn><accession-num>25798657</accession-num><urls><related-urls><url> Concerning reliability, within-subject variability in spontaneous BRS is high ADDIN EN.CITE <EndNote><Cite><Author>Maestri</Author><Year>2009</Year><RecNum>137</RecNum><DisplayText><style face="superscript">44</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485177976">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Maestri, R.</author><author>Raczak, G.</author><author>Torunski, A.</author><author>Sukiennik, A.</author><author>Kozlowski, D.</author><author>La Rovere, M. T.</author><author>Pinna, G. D.</author></authors></contributors><auth-address>Department of Cardiology and Biomedical Engineering, S. Maugeri Foundation-IRCCS, Scientific Institute of Montescano, Montescano, Pavia, Italy. roberto.maestri@fsm.it</auth-address><titles><title>Day-by-day variability of spontaneous baroreflex sensitivity measurements: implications for their reliability in clinical and research applications</title><secondary-title>J Hypertens</secondary-title></titles><periodical><full-title>J Hypertens</full-title></periodical><pages>806-12</pages><volume>27</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Myocardial Infarction/physiopathology</keyword><keyword>Reproducibility of Results</keyword><keyword>Sample Size</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2009</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1473-5598 (Electronic)
0263-6352 (Linking)</isbn><accession-num>19300111</accession-num><urls><related-urls><url>; however, spontaneous BRS remains a more reliable measure of cardiac autonomic control than other non-invasive measures, such as heart rate variability ADDIN EN.CITE <EndNote><Cite><Author>Pinna</Author><Year>2007</Year><RecNum>136</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>136</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485177974">136</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pinna, G. D.</author><author>Maestri, R.</author><author>Torunski, A.</author><author>Danilowicz-Szymanowicz, L.</author><author>Szwoch, M.</author><author>La Rovere, M. T.</author><author>Raczak, G.</author></authors></contributors><auth-address>Department of Cardiology and Biomedical Engineering, S. Maugeri Foundation-IRCCS, Scientific Institute of Montescano, Montescano (PV), Italy. gdpinna@fsm.it</auth-address><titles><title>Heart rate variability measures: a fresh look at reliability</title><secondary-title>Clin Sci (Lond)</secondary-title></titles><periodical><full-title>Clin Sci (Lond)</full-title></periodical><pages>131-40</pages><volume>113</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Electrocardiography/methods</keyword><keyword>Female</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Reproducibility of Results</keyword><keyword>Respiratory Mechanics/physiology</keyword><keyword>Signal Processing, Computer-Assisted</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1470-8736 (Electronic)
0143-5221 (Linking)</isbn><accession-num>17381425</accession-num><urls><related-urls><url>. The cross-correlation of the baroreflex sensitivity method described by Westerhof et al. significantly increases both the measurability and reliability of BRS estimation. ADDIN EN.CITE <EndNote><Cite><Author>Westerhof</Author><Year>2004</Year><RecNum>138</RecNum><DisplayText><style face="superscript">46</style></DisplayText><record><rec-number>138</rec-number><foreign-keys><key app="EN" db-id="ftvpt2aw9z0vxfeavt4xvwvyzvtaxptv5e09" timestamp="1485177978">138</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Westerhof, B. E.</author><author>Gisolf, J.</author><author>Stok, W. J.</author><author>Wesseling, K. H.</author><author>Karemaker, J. M.</author></authors></contributors><auth-address>TNO-TPD-Biomedical Instrumentation, Academic Medical Centre, University of Amsterdam, The Netherlands. westerhof@tpd.tno.nl</auth-address><titles><title>Time-domain cross-correlation baroreflex sensitivity: performance on the EUROBAVAR data set</title><secondary-title>J Hypertens</secondary-title></titles><periodical><full-title>J Hypertens</full-title></periodical><pages>1371-80</pages><volume>22</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/*physiology</keyword><keyword>Diabetic Neuropathies/physiopathology</keyword><keyword>Female</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Heart Transplantation</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/physiopathology</keyword><keyword>Hypertension/diagnosis/*physiopathology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Posture/*physiology</keyword><keyword>Reaction Time</keyword></keywords><dates><year>2004</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0263-6352 (Print)
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ADDIN EN.CITE.DATA 3-7The administration of vasoactive drugs elicits acute changes in AP EKG and SAP waveforms are recorded simultaneously, then beat-to-beat SAP and calculated RRI are plotted.BRS is defined as the slope of a regression line fitted on a scatter plot of SAP and RRI corresponding pairs of values.Estimates the vagal component of BRS with vasopressor drugs (e.g., phenylephrine) or the sympathetic component with vasorelaxing drugs (e.g. nitroglycerin, amyl nitrite).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYSBSb3ZlcmU8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFy
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ADDIN EN.CITE.DATA 7,8Difficult to select the exact moments at which SAP and RRI change following the administration of the vasoactive drug. ADDIN EN.CITE <EndNote><Cite><Author>Kuusela</Author><Year>2012</Year><RecNum>2464</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>2464</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1509044097">2464</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Kuusela, T.A.</author></authors><secondary-authors><author>Kamath, M.; Watanabe, M.; Upton A.</author></secondary-authors></contributors><titles><title>Methodological Aspects of Baroreflex Sensitivity Analysis</title><secondary-title>Heart Rate Variability (HRV) Signal Analysis: Clinical Applications
</secondary-title></titles><pages>43–58</pages><section>3</section><dates><year>2012</year></dates><publisher>CRC Press </publisher><isbn>Print ISBN: 978-1-4398-4980-4
eBook ISBN: 978-1-4665-7605-6</isbn><urls></urls><electronic-resource-num>10.1201/b12756-5</electronic-resource-num></record></Cite></EndNote>4Phenylephrine method assesses only part of the baroreflex arc: maximal baroreceptor recruitment by large changes in SAP (phasic component) but not the minimal activation from natural SAP oscillations (tonic component). ADDIN EN.CITE <EndNote><Cite><Author>Davies</Author><Year>2001</Year><RecNum>2395</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>2395</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1508953216">2395</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Davies, L. C.</author><author>Francis, D. P.</author><author>Scott, A. C.</author><author>Ponikowski, P.</author><author>Piepoli, M.</author><author>Coats, A. J.</author></authors></contributors><auth-address>National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, UK. ceri@davies151.freeserve.co.uk</auth-address><titles><title>Effect of altering conditions of the sequence method on baroreflex sensitivity</title><secondary-title>J Hypertens</secondary-title></titles><periodical><full-title>Journal of Hypertension</full-title><abbr-1>J. Hypertens.</abbr-1><abbr-2>J Hypertens</abbr-2></periodical><pages>1279-87</pages><volume>19</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure</keyword><keyword>Cardiac Output, Low/*physiopathology</keyword><keyword>Cardiology/*methods</keyword><keyword>Chronic Disease</keyword><keyword>Differential Threshold</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Reference Values</keyword></keywords><dates><year>2001</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0263-6352 (Print)
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ADDIN EN.CITE.DATA 7Acute changes in AP are elicited by physiological maneuvers (Valsalva phase 4 or pressure-vacuum on the neck region).BRS is estimated by slope measurement similar to the pharmacological methods.Is an alternative when the administration of vasoactive drugs is not possible.Valsalva maneuver should not be used in patients with advanced ventricular dysfunction.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYSBSb3ZlcmU8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFy
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ADDIN EN.CITE.DATA 7Sequence method PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYXZpZXM8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 6,11-16A time-domain based analysis of a time series that identifies sequences of increase in SAP and RRI (Up sequence) or decrease in SAP and RRI (Down sequence). Sequence linear slopes are then estimated and averaged.Selection of sequences ≥ 3 beats is based on empirically setting SAP, RRI, and correlation coefficient thresholds.Breathing is either paced with a metronome during measurement or adjusted for the respiratory rate by estimating it from the peak amplitude of high frequency HRV.Estimates the spontaneous BRS from naturally occurring fluctuations of SAP. It does not require the use of vasoactive pharmacological agents.Allows to assess asymmetric impairment of bradycardic and tachycardic baroreflexes as seen in diabetics.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KYXZvcmthPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA 17Its long-term reliability is higher than cross-spectral analysis for some pathological conditions, e.g., chronic heart failure. ADDIN EN.CITE <EndNote><Cite><Author>Herpin</Author><Year>1997</Year><RecNum>2467</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>2467</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1509044736">2467</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Herpin, D.</author><author>Ragot, S.</author></authors></contributors><auth-address>Service Cardiologie, Centre Hospitalo-Universitaire, Poitiers, France.</auth-address><titles><title>Mid- and long-term reproducibility of noninvasive measurements of spontaneous arterial baroreflex sensitivity in healthy volunteers</title><secondary-title>Am J Hypertens</secondary-title><alt-title>American journal of hypertension</alt-title></titles><periodical><full-title>American Journal of Hypertension</full-title><abbr-1>Am. J. Hypertens.</abbr-1><abbr-2>Am J Hypertens</abbr-2></periodical><alt-periodical><full-title>American Journal of Hypertension</full-title><abbr-1>Am. J. Hypertens.</abbr-1><abbr-2>Am J Hypertens</abbr-2></alt-periodical><pages>790-7</pages><volume>10</volume><number>7 Pt 1</number><edition>1997/07/01</edition><keywords><keyword>Adult</keyword><keyword>Arteries/*physiology</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/physiology</keyword><keyword>Female</keyword><keyword>Heart Rate/physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Photoplethysmography</keyword><keyword>Posture/physiology</keyword><keyword>Reproducibility of Results</keyword></keywords><dates><year>1997</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0895-7061 (Print)
0895-7061</isbn><accession-num>9234835</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>14Underestimates and overestimated BRS compared with phenylephrine and nitroprusside slope methods, respectively. ADDIN EN.CITE <EndNote><Cite><Author>Johnson</Author><Year>2006</Year><RecNum>2401</RecNum><DisplayText><style face="superscript">18</style></DisplayText><record><rec-number>2401</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1508953217">2401</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Johnson, P.</author><author>Shore, A.</author><author>Potter, J.</author><author>Panerai, R.</author><author>James, M.</author></authors></contributors><auth-address>Dept. of Medicine for the Elderly, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK. paul.johnson@pms.ac.uk</auth-address><titles><title>Baroreflex sensitivity measured by spectral and sequence analysis in cerebrovascular disease : methodological considerations</title><secondary-title>Clin Auton Res</secondary-title></titles><periodical><full-title>Clinical Autonomic Research</full-title><abbr-1>Clin. Auton. Res.</abbr-1><abbr-2>Clin Auton Res</abbr-2></periodical><pages>270-5</pages><volume>16</volume><number>4</number><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/physiology</keyword><keyword>Cerebrovascular Disorders/diagnostic imaging/*physiopathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Physiologic/methods</keyword><keyword>Reproducibility of Results</keyword><keyword>Stroke/diagnostic imaging/physiopathology</keyword><keyword>Ultrasonography</keyword></keywords><dates><year>2006</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0959-9851 (Print)
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ADDIN EN.CITE.DATA 16Number of sequences could be reduced or absent in a 5-minute period in patients with impaired BRS (diabetics, hypertensives). ADDIN EN.CITE <EndNote><Cite><Author>Davies</Author><Year>2001</Year><RecNum>2395</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>2395</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1508953216">2395</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Davies, L. C.</author><author>Francis, D. P.</author><author>Scott, A. C.</author><author>Ponikowski, P.</author><author>Piepoli, M.</author><author>Coats, A. J.</author></authors></contributors><auth-address>National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, UK. ceri@davies151.freeserve.co.uk</auth-address><titles><title>Effect of altering conditions of the sequence method on baroreflex sensitivity</title><secondary-title>J Hypertens</secondary-title></titles><periodical><full-title>Journal of Hypertension</full-title><abbr-1>J. Hypertens.</abbr-1><abbr-2>J Hypertens</abbr-2></periodical><pages>1279-87</pages><volume>19</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure</keyword><keyword>Cardiac Output, Low/*physiopathology</keyword><keyword>Cardiology/*methods</keyword><keyword>Chronic Disease</keyword><keyword>Differential Threshold</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Reference Values</keyword></keywords><dates><year>2001</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0263-6352 (Print)
0263-6352 (Linking)</isbn><accession-num>11446718</accession-num><urls><related-urls><url> sensitivity than phenylephrine method to detect differences if a residual BRS is sufficient to control small SAP oscillations of ± 5 mmHg. ADDIN EN.CITE <EndNote><Cite><Author>Watkins</Author><Year>1995</Year><RecNum>2428</RecNum><DisplayText><style face="superscript">8</style></DisplayText><record><rec-number>2428</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1508953218">2428</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Watkins, L. L.</author><author>Fainman, C.</author><author>Dimsdale, J.</author><author>Ziegler, M. G.</author></authors></contributors><auth-address>Department of Psychiatry, University of California-San Diego, La Jolla, USA.</auth-address><titles><title>Assessment of baroreflex control from beat-to-beat blood pressure and heart rate changes: a validation study</title><secondary-title>Psychophysiology</secondary-title></titles><periodical><full-title>Psychophysiology</full-title><abbr-1>Psychophysiology</abbr-1><abbr-2>Psychophysiology</abbr-2></periodical><pages>411-4</pages><volume>32</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Baroreflex/drug effects/*physiology/radiation effects</keyword><keyword>Blood Pressure/drug effects/*physiology</keyword><keyword>Female</keyword><keyword>Heart Rate/drug effects/*physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nitrates/pharmacology</keyword><keyword>Oropharyngeal Neoplasms/radiotherapy</keyword><keyword>Pentanols/pharmacology</keyword><keyword>Phenylephrine/pharmacology</keyword><keyword>Radiotherapy/adverse effects</keyword></keywords><dates><year>1995</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0048-5772 (Print)
0048-5772 (Linking)</isbn><accession-num>7652118</accession-num><urls><related-urls><url> values are differentially affected by sequence selection criteria in healthy subjects vs. patients (e.g., chronic heart failure). ADDIN EN.CITE <EndNote><Cite><Author>Davies</Author><Year>2001</Year><RecNum>2395</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>2395</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1508953216">2395</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Davies, L. C.</author><author>Francis, D. P.</author><author>Scott, A. C.</author><author>Ponikowski, P.</author><author>Piepoli, M.</author><author>Coats, A. J.</author></authors></contributors><auth-address>National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, UK. ceri@davies151.freeserve.co.uk</auth-address><titles><title>Effect of altering conditions of the sequence method on baroreflex sensitivity</title><secondary-title>J Hypertens</secondary-title></titles><periodical><full-title>Journal of Hypertension</full-title><abbr-1>J. Hypertens.</abbr-1><abbr-2>J Hypertens</abbr-2></periodical><pages>1279-87</pages><volume>19</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure</keyword><keyword>Cardiac Output, Low/*physiopathology</keyword><keyword>Cardiology/*methods</keyword><keyword>Chronic Disease</keyword><keyword>Differential Threshold</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Reference Values</keyword></keywords><dates><year>2001</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0263-6352 (Print)
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ADDIN EN.CITE.DATA 7,14,19-25A frequency-domain based analysis in which time-localized RRI and SAP signals (times series) are converted to a frequency sequence. Algorithms then compute SAP and RRI power spectra (e.g., fast Fourier transform, transfer function, autoregressive).Assumes that SAP is mainly associated with the integral of the spectrum over 0.04 -0.15 Hz (LF band).BRS is generally estimated as either the square root of the ratio between RRI and SAP spectral powers (autoregressive method), or the average of the transfer function modulus (the gain) between SAP and RRI, over the LF band frequencies with coherence ≥0.5. Non‐baroreflex interactions (influences of RRI on SAP) can be removed by separately computing the unidirectional causal coherence and gain for SAP on RRI (bivariate autoregressive model).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PbmRydXNvdmE8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFy
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ADDIN EN.CITE.DATA 24,25Estimates the spontaneous BRS from naturally occurring fluctuations of BP.Ascertains that both SAP and RRI signals have the same frequency components and phase relationships can be taken into consideration.Using transfer function, allows estimation of BRS with clinical accuracy, under conditions of low signal-to-noise ratio and/or impaired baroreflex gain associated with markedly reduced coherence.Allows for reducing the influence of non-baroreflex components on BRS estimates.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PbmRydXNvdmE8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFy
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ADDIN EN.CITE.DATA 24,26Reproducibility of results within one-week interval. ADDIN EN.CITE <EndNote><Cite><Author>Herpin</Author><Year>1997</Year><RecNum>2467</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>2467</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1509044736">2467</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Herpin, D.</author><author>Ragot, S.</author></authors></contributors><auth-address>Service Cardiologie, Centre Hospitalo-Universitaire, Poitiers, France.</auth-address><titles><title>Mid- and long-term reproducibility of noninvasive measurements of spontaneous arterial baroreflex sensitivity in healthy volunteers</title><secondary-title>Am J Hypertens</secondary-title><alt-title>American journal of hypertension</alt-title></titles><periodical><full-title>American Journal of Hypertension</full-title><abbr-1>Am. J. Hypertens.</abbr-1><abbr-2>Am J Hypertens</abbr-2></periodical><alt-periodical><full-title>American Journal of Hypertension</full-title><abbr-1>Am. J. Hypertens.</abbr-1><abbr-2>Am J Hypertens</abbr-2></alt-periodical><pages>790-7</pages><volume>10</volume><number>7 Pt 1</number><edition>1997/07/01</edition><keywords><keyword>Adult</keyword><keyword>Arteries/*physiology</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/physiology</keyword><keyword>Female</keyword><keyword>Heart Rate/physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Photoplethysmography</keyword><keyword>Posture/physiology</keyword><keyword>Reproducibility of Results</keyword></keywords><dates><year>1997</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0895-7061 (Print)
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ADDIN EN.CITE.DATA 7Difficult to use in pathological conditions with low coherence (e.g., chronic heart failure). ADDIN EN.CITE <EndNote><Cite><Author>Colombo</Author><Year>1999</Year><RecNum>2391</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>2391</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1508953216">2391</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Colombo, R.</author><author>Mazzuero, G.</author><author>Spinatonda, G.</author><author>Lanfranchi, P.</author><author>Giannuzzi, P.</author><author>Ponikowski, P.</author><author>Coats, A. J.</author><author>Minuco, G.</author></authors></contributors><auth-address>'Salvatore Maugeri' Foundation, IRCCS, Service of Bioengineering, Veruno (NO), Italy. rcolombo@fsm.it</auth-address><titles><title>Comparison between spectral analysis and the phenylephrine method for the assessment of baroreflex sensitivity in chronic heart failure</title><secondary-title>Clin Sci (Lond)</secondary-title></titles><periodical><full-title>Clinical Science (London, England: 1979)</full-title><abbr-1>Clin. Sci. (Lond.)</abbr-1><abbr-2>Clin Sci (Lond)</abbr-2></periodical><pages>503-13</pages><volume>97</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Heart Failure/*physiopathology</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Models, Cardiovascular</keyword><keyword>*Phenylephrine</keyword><keyword>Regression Analysis</keyword><keyword>Reproducibility of Results</keyword><keyword>Respiration</keyword><keyword>*Signal Processing, Computer-Assisted</keyword><keyword>*Vasoconstrictor Agents</keyword></keywords><dates><year>1999</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0143-5221 (Print)
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ADDIN EN.CITE.DATA 27,28A linear model with one output signal: RRI (autoregressive component), two input signals: SAP and instantaneous lung volume (moving average component), and two uncorrelated sources of noise from SAP and respiration. Breathing guided by a randomly spaced sequence of computer-generated tones since the broadband input is thought to be required for a solution with the model.Estimates BRS without the influence of respiration and the noise component by enabling a separate evaluation of causal coherence and gains in two directions: from SAP to RRI and from RRI to SAP.Is highly reproducible within one-week period and significantly correlated with BRS derived from the sequence method and slope method with hypotensive drug (but not with hypertensive drugs). ADDIN EN.CITE <EndNote><Cite><Author>O'Leary</Author><Year>1999</Year><RecNum>2471</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>2471</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1509048340">2471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>O'Leary, D. D.</author><author>Lin, D. C.</author><author>Hughson, R. L.</author></authors></contributors><auth-address>Department of Kinesiology, University of Waterloo, Ontario, Canada.</auth-address><titles><title>Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing</title><secondary-title>Clin Physiol</secondary-title><alt-title>Clinical physiology (Oxford, England)</alt-title></titles><periodical><full-title>Clinical Physiology</full-title><abbr-1>Clin. Physiol.</abbr-1><abbr-2>Clin Physiol</abbr-2></periodical><pages>369-77</pages><volume>19</volume><number>5</number><edition>1999/10/12</edition><keywords><keyword>Adult</keyword><keyword>Analysis of Variance</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/*physiology</keyword><keyword>Electrophysiology/methods</keyword><keyword>Female</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Reproducibility of Results</keyword><keyword>*Respiration</keyword></keywords><dates><year>1999</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0144-5979 (Print)
0144-5979</isbn><accession-num>10516887</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>28Some individuals are unable to followthe tones because of cognitive deficit and/or pulmonary disease. Yet, meaningful estimation could be obtained under spontaneous breathing. ADDIN EN.CITE <EndNote><Cite><Author>O'Leary</Author><Year>1999</Year><RecNum>2471</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>2471</rec-number><foreign-keys><key app="EN" db-id="s2ptppz9x0zedne0sxo5d0dcertvp99ffe05" timestamp="1509048340">2471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>O'Leary, D. D.</author><author>Lin, D. C.</author><author>Hughson, R. L.</author></authors></contributors><auth-address>Department of Kinesiology, University of Waterloo, Ontario, Canada.</auth-address><titles><title>Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing</title><secondary-title>Clin Physiol</secondary-title><alt-title>Clinical physiology (Oxford, England)</alt-title></titles><periodical><full-title>Clinical Physiology</full-title><abbr-1>Clin. Physiol.</abbr-1><abbr-2>Clin Physiol</abbr-2></periodical><pages>369-77</pages><volume>19</volume><number>5</number><edition>1999/10/12</edition><keywords><keyword>Adult</keyword><keyword>Analysis of Variance</keyword><keyword>Baroreflex/*physiology</keyword><keyword>Blood Pressure/*physiology</keyword><keyword>Electrophysiology/methods</keyword><keyword>Female</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Reproducibility of Results</keyword><keyword>*Respiration</keyword></keywords><dates><year>1999</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0144-5979 (Print)
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ADDIN EN.CITE.DATA 29,30A non-linear model that provides time-dependent changes in amplitude and phase of a particular frequency component as a function of time.BRS is estimated by the instantaneous amplitude of complex-demodulated RRI divided by the instantaneous amplitude of complex-demodulated SAP.Produces a frequency range of 0.04 to 0.14 Hz (LF band) when applied to RRI and SAP signals a center frequency of 0.09 Hz with cutoff frequency of low-pass filter of 0.05 Hz.Allows modeling the non-lineal features of the arterial baroreflex, which naturally exhibits a sigmoidal stimulus (SAP)–response (RRI) curve.Has a high temporal resolution of about 15 s, which is better than any seen in spectral method.Useful for ambulatory, not very clean, recordings since stationary condition for the time series is not required. BRS values are quite stable.Results are equivalent to those derived by cross-spectral and sequential analysis.Has no control over whether the signals are coherent concerning each other or whether a change in the SAP signal precedes a change in the RR interval.Note: ECG: electrocardiogram, AP: arterial blood pressure, BRS: baroreflex sensitivity, SAP: systolic arterial pressure, RRI: R-R interval, LF: low-frequency, HRV: heart rate variabilityFIGURE 1S: Estimation of BRS using the sequence method. EKG and SAP waveforms are recorded simultaneously, then beat-to-beat SAP and the calculated RRI are plotted against time course. A. SAP and RR interval signals and the baroreflex sequences acquired using the sequence method. Closed squares indicate UP sequences. Open squares indicate DOWN sequences. Sequence selection criteria: SAP > 0.5 mmHg, RRI > 1 ms, sequence > 3, a significant correlation coefficient (r > 0.9). Note that the significant sequences cluster in segments where SAP and RRI signals apparently oscillate more coherently (in this case, at the start and the end of this recording.). B. Within-subject variability of the BRS. Mean UP, DOWN, and overall BRS calculated from the sequences shown in the previous figure.REFERENCES ADDIN EN.REFLIST 1.Parati G, Di Rienzo M, Mancia G: How to measure baroreflex sensitivity: from the cardiovascular laboratory to daily life. J Hypertens 2000; 18: 7-192.Reyes Del Paso GA, Gonzales MI, Hernandez JA: Comparison of baroreceptor cardiac reflex sensivity estimates from intersystolic and ECG R-R intervals. Psychophysiology 2010; 47: 1102-11083.Smyth HS, Sleight P, Pickering GW: Reflex regulation of arterial pressure during sleep in man. A quantitative method of assessing baroreflex sensitivity. 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