On the validity of the state space correspondence strategy based on k-nearest neighbor cross-predictability in assessing directionality in stochastic systems: Application to cardiorespiratory coupling estimation.

We tested the validity of the state space correspondence (SSC) strategy based on k-nearest neighbor cross-predictability (KNNCP) to assess the directionality of coupling in stochastic nonlinear bivariate autoregressive (NBAR) processes. The approach was applied to assess closed-loop cardiorespiratory interactions between heart period (HP) variability and respiration (R) during a controlled respiration (CR) protocol in 19 healthy humans (aged from 27 to 35 yrs, 11 females) and during active standing (STAND) in 25 athletes (aged from 20 to 40 yrs, all men) and 25 non-athletes (aged from 20 to 40 yrs, all men). Over simulated NBAR processes, we found that (i) the SSC approach can detect the correct causal relationship as the direction leads to better KNNCP from the past of the driver to the future state of the target and (ii) simulations suggest that the ability of the method is preserved in any condition of complexity of the interacting series. Over CR and STAND protocols, we found that (a) slowing the breathing rate increases the strength of the causal relationship in both temporal directions in a balanced modality; (b) STAND is more powerful in modulating the coupling strength on the pathway from HP to R; (c) regardless of protocol and experimental condition, the strength of the link from HP to R is stronger than that from R to HP; (d) significant causal relationships in both temporal directions are found regardless of the level of complexity of HP variability and R. The SSC strategy is useful to disentangle closed-loop cardiorespiratory interactions.

Autonomic Function and Baroreflex Control in COVID-19 Patients Admitted to the Intensive Care Unit.

Background: Autonomic function and baroreflex control might influence the survival rate of coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to respiratory failure patients without COVID-19 (non-COVID-19). This study describes physiological control mechanisms in critically ill COVID-19 patients admitted to the ICU in comparison to non-COVID-19 individuals with the aim of improving stratification of mortality risk. Methods: We evaluated autonomic and baroreflex control markers extracted from heart period (HP) and systolic arterial pressure (SAP) variability acquired at rest in the supine position (REST) and during a modified head-up tilt (MHUT) in 17 COVID-19 patients (age: 63 ± 10 years, 14 men) and 33 non-COVID-19 patients (age: 60 ± 12 years, 23 men) during their ICU stays. Patients were categorized as survivors (SURVs) or non-survivors (non-SURVs). Results: We found that COVID-19 and non-COVID-19 populations exhibited similar vagal and sympathetic control markers; however, non-COVID-19 individuals featured a smaller baroreflex sensitivity and an unexpected reduction in the HP-SAP association during the MHUT compared to the COVID-19 group. Nevertheless, none of the markers of the autonomic and baroreflex functions could distinguish SURVs from non-SURVs in either population. Conclusions: We concluded that COVID-19 patients exhibited a more preserved baroreflex control compared to non-COVID-19 individuals, even though this information is ineffective in stratifying mortality risk.

Cardiorespiratory coupling is associated with exercise capacity in athletes: A cross-sectional study.

PURPOSE: To determine the association between exercise capacity based on peak oxygen uptake (VO2peak) and resting cardiorespiratory coupling (CRC) levels in athletes and non-athletes' subjects. METHODS: A cross-sectional study was carried out in 42 apparently healthy male subjects, aged between 20 and 40 years old. The participants were allocated into athletes (n = 21) and non-athletes (n = 21) groups. Resting electrocardiogram and respiratory movement (RESP) were simultaneously acquired during 15 min in supine position and quiet breathing. The beat-to-beat heart period (HP) and RESP series were determined from the recorded signals. Traditional analysis of HP based on frequency domain indexes was performed considering the high-frequency (0.15 - 0.45 Hz) components. To compute the CRC, the linear association between HP and RESP series was determined via squared coherence function and directionality of interaction was investigated through the causal extension of this approach. The exercise capacity was assessed through incremental cardiopulmonary exercise testing in order to determine the VO2peak. RESULTS: Traditional analysis of HP based on high-frequency index was not correlated with exercise capacity in the athletes (r = -0.1, p = 0.5) and non-athletes (r = -0.1, p = 0.3) cohorts. However, resting CRC values was associated with exercise capacity in athletes (r = 0.4, p = 0.03), but not in the non-athletes group (r = -0.2, p = 0.3). CONCLUSION: These results suggest that improved resting values of CRC is associated with higher exercise capacity (VO2peak) in endurance athletes. Moreover, frequency domain of HP was not sensitive to identifying this relationship, probably because effects of training on parasympathetic modulation might be affected by respiratory dynamics, and this influence has a directionality (i.e., from RESP to HP).

Link Between Cardiovascular and Cerebrovascular Controls in Patients Undergoing Surgical Aortic Valve Replacement.

Although the autonomic influence on cardiovascular (CV) and cerebrovascular (CBV) regulations has been widely recognized, their relationship is poorly explored especially in pathological situations. This study investigates the correlation between CV and CBV markers in 73 patients (48 males, age 63.6±13.1 yrs) undergoing surgical aortic valve replacement (SAVR) evaluated before the intervention (PRE), within 1-week post-surgery (POST) and after a 3-month follow-up (POST3). Patients were acquired before and after an orthostatic challenge. Frequency domain analysis assessing transfer function gain (TFG), phase (Ph), and squared coherence (K2) between heart period and systolic arterial pressure was exploited to evaluate CV control. The same frequency domain functions were derived to assess CBV regulation from mean cerebral blood velocity and mean arterial pressure. A correlation analysis between indexes of CV and CBV controls was carried out. Results showed that CV control was impaired in PRE, worsened in POST, and recovered in POST3, while CBV markers were almost unchanged. A significant positive relationship between CV and CBV markers was observed, especially in POST and POST3, thus suggesting that the compensation of a baroreflex impairment with a more efficient CBV control and vice versa. The maintenance of this relationship between CV and CBV controls in patients undergoing SAVR could be fundamental to prevent risky situations.Clinical Relevance- After surgical aortic valve replacement an impaired baroreflex control could be compensated by a more efficient cerebral autoregulation.

On the Validity of Single Regression Strategy for Granger Causality Assessment in Cardiovascular and Cardiorespiratory Control Studies.

Granger causality (GC) analysis is based on the comparison between prediction error variances computed over the full and restricted models after identifying the coefficients of appropriate vector regressions. GC markers can be computed via a double regression (DR) approach identifying two separate, independent models and a single regression (SR) strategy optimizing the description of the dynamics of the target over the full model and, then, reusing some parts of it in the restricted model. The present study compares the SR and DR strategies over heart period (HP), systolic arterial pressure (SAP) and respiration (R) beat-to-beat series collected during a graded orthostatic challenge induced by head-up tilt in 17 healthy individuals (age: 21-36 yrs; median: 29 yrs; 9 females and 8 males). We found that the DR approach was more powerful than the SR one in detecting the expected stronger involvement of the baroreflex during the challenge, while the expected weaker cardiorespiratory coupling was identified by both SR and DR strategies. The less powerful ability of the SR approach was the result of the greater variance of GC markers compared to the DR strategy. We conclude that, contrary to the suggestions present in literature, the SR approach is not necessarily associated with a smaller dispersion of GC markers. Moreover, we suggest that additional factors, such as the strategy utilized to build embedding spaces and metric utilized to compare prediction error variances, might play an important role in differentiating SR and DR approaches.

Characterization of Multiple Regimes of Cardiorespiratory Phase Synchronization in Athletes Undergoing Inspiratory Muscle Training.

Cardiorespiratory phase synchronization (CRPS) is defined as the stable occurrence of n heartbeats within m respiratory cycles according to the n:m phase locking ratio (PLR). Since CRPS is an intermittent phenomenon where different phase synchronization regimes and epochs of phase unlocking can alternate within the same recording, an index of CRPS ideally should assess all potential PLRs present in the recording. However, traditional approaches compute the synchronization index (SYNC%) over a single n:m PLR, namely the one that maximizes CRPS. In the present work, we tested a synchronization index assessing the total percentage of heartbeats coupled to the inspiratory onset regardless of phase locking regimes (SYNC%sum) and we compared its efficacy to the more traditional SYNC%. Analysis was carried out in a cohort of 25 male amateur cyclists (age: 20-40 yrs) undergoing inspiratory muscle training (IMT) at different intensities. CRPS was assessed before and after the IMT protocol, during an experimental condition known to modify CRPS, namely active standing (STAND). We found that after a moderate intensity IMT at 60% of the maximal inspiratory pressure, SYNC%sum could detect the decrease in CRPS following STAND. This result was not visible using the more traditional SYNC%. Therefore, we stress the significant presence of different phase locking regimes in athletes and the importance of accounting for multiple PLRs in CRPS analysis.Clinical Relevance- Multiple phase locking regimes contribute significantly to cardiorespiratory control in amateur cyclists especially after inspiratory muscle training of moderate intensity.

The degree of engagement of cardiac and sympathetic arms of the baroreflex does not depend on the absolute value and sign of arterial pressure variations.

Objective.The percentages of cardiac and sympathetic baroreflex patterns detected via baroreflex sequence (SEQ) technique from spontaneous variability of heart period (HP) and systolic arterial pressure (SAP) and of muscle nerve sympathetic activity (MSNA) burst rate and diastolic arterial pressure (DAP) are utilized to assess the level of the baroreflex engagement. The cardiac baroreflex patterns can be distinguished in those featuring both HP and SAP increases (cSEQ++) and decreases (cSEQ--), while the sympathetic baroreflex patterns in those featuring a MSNA burst rate decrease and a DAP increase (sSEQ+-) and vice versa (sSEQ-+). The present study aims to assess the modifications of the involvement of the cardiac and sympathetic arms of the baroreflex with age and postural stimulus intensity.Approach.We monitored the percentages of cSEQ++ (%cSEQ++) and cSEQ-- (%cSEQ--) in 100 healthy subjects (age: 21-70 years, 54 males, 46 females), divided into five sex-balanced groups consisting of 20 subjects in each decade at rest in supine position and during active standing (STAND). We evaluated %cSEQ++, %cSEQ--, and the percentages of sSEQ+- (%sSEQ+-) and sSEQ-+ (%sSEQ-+) in 12 young healthy subjects (age 23 ± 2 years, 3 females, 9 males) undergoing incremental head-up tilt.Main results.We found that: (i) %cSEQ++ and %cSEQ-- decreased with age and increased with STAND and postural stimulus intensity; (ii) %sSEQ+- and %sSEQ-+ augmented with postural challenge magnitude; (iii) the level of cardiac and sympathetic baroreflex engagement did not depend on either the absolute value of arterial pressure or the direction of its changes.Significance.This study stresses the limited ability of the cardiac and sympathetic arms of the baroreflex in controlling absolute arterial pressure values and the equivalent ability of both positive and negative arterial pressure changes in soliciting them.

Characterization of cardiovascular and cerebrovascular controls via spectral causality analysis in patients undergoing surgical aortic valve replacement during a three-month follow-up.

Objective.Aortic valve stenosis (AVS) induces left ventricular function adaptations and surgical aortic valve replacement (SAVR) restores blood flow profile across aortic valve. Modifications of cardiac hemodynamics induced by AVS and SAVR might alter cardiovascular (CV) and cerebrovascular (CBV) controls. The study aims at characterizing CV and CBV regulations one day before SAVR (PRE), within one week after SAVR (POST), and after a three-month follow-up (POST3) in 73 AVS patients (age: 63.9 ± 12.9 yrs; 48 males, 25 females) from spontaneous fluctuations of heart period (HP), systolic arterial pressure, mean arterial pressure and mean cerebral blood velocity.Approach.CV and CBV regulations were typified via a bivariate autoregressive approach computing traditional frequency domain markers and causal squared coherence (CK2) from CV and CBV variabilities. Univariate time and frequency domain indexes were calculated as well. Analyses were carried out in frequency bands typical of CV and CBV controls at supine rest and during active standing. A surrogate method was exploited to check uncoupling condition.Main results.We found that: (i) CV regulation is impaired in AVS patients; (ii) CV regulation worsens in POST; (iii) CV regulation recovers in POST3 and CV response to active standing is even better than in PRE; (iv) CBV regulation is preserved in AVS patients; (v) SAVR does not affect CBV control; (vi) parameters of the CBV control in POST3 and PRE are similar.Significance.CK2is particularly useful to characterize CV and CBV controls in AVS patients and to monitor of patient's evolution after SAVR.

Assessing cardiorespiratory interactions via lagged joint symbolic dynamics during spontaneous and controlled breathing.

Introduction: Joint symbolic analysis (JSA) can be utilized to describe interactions between time series while accounting for time scales and nonlinear features. JSA is based on the computation of the rate of occurrence of joint patterns built after symbolization. Lagged JSA (LJSA) is obtained from the more classical JSA by introducing a delay/lead between patterns built over the two series and combined to form the joint scheme, thus monitoring coordinated patterns at different lags. Methods: In the present study, we applied LJSA for the assessment of cardiorespiratory coupling (CRC) from heart period (HP) variability and respiratory activity (R) in 19 healthy subjects (age: 27-35 years; 8 males, 11 females) during spontaneous breathing (SB) and controlled breathing (CB). The R rate of CB was selected to be indistinguishable from that of SB, namely, 15 breaths·minute-1 (CB15), or slower than SB, namely, 10 breaths·minute-1 (CB10), but in both cases, very rapid interactions between heart rate and R were known to be present. The ability of the LJSA approach to follow variations of the coupling strength was tested over a unidirectionally or bidirectionally coupled stochastic process and using surrogate data to test the null hypothesis of uncoupling. Results: We found that: i) the analysis of surrogate data proved that HP and R were significantly coupled in any experimental condition, and coupling was not more likely to occur at a specific time lag; ii) CB10 reduced CRC strength at the fastest time scales while increasing that at intermediate time scales, thus leaving the overall CRC strength unvaried; iii) despite exhibiting similar R rates and respiratory sinus arrhythmia, SB and CB15 induced different cardiorespiratory interactions; iv) no dominant temporal scheme was observed with relevant contributions of HP patterns either leading or lagging R. Discussion: LJSA is a useful methodology to explore HP-R dynamic interactions while accounting for time shifts and scales.

Concomitant evaluation of cardiovascular and cerebrovascular controls via Geweke spectral causality to assess the propensity to postural syncope.

The evaluation of propensity to postural syncope necessitates the concomitant characterization of the cardiovascular and cerebrovascular controls and a method capable of disentangling closed loop relationships and decomposing causal links in the frequency domain. We applied Geweke spectral causality (GSC) to assess cardiovascular control from heart period and systolic arterial pressure variability and cerebrovascular regulation from mean arterial pressure and mean cerebral blood velocity variability in 13 control subjects and 13 individuals prone to develop orthostatic syncope. Analysis was made at rest in supine position and during head-up tilt at 60°, well before observing presyncope signs. Two different linear model structures were compared, namely bivariate autoregressive and bivariate dynamic adjustment classes. We found that (i) GSC markers did not depend on the model structure; (ii) the concomitant assessment of cardiovascular and cerebrovascular controls was useful for a deeper comprehension of postural disturbances; (iii) orthostatic syncope appeared to be favored by the loss of a coordinated behavior between the baroreflex feedback and mechanical feedforward pathway in the frequency band typical of the baroreflex functioning during the postural challenge, and by a weak cerebral autoregulation as revealed by the increased strength of the pressure-to-flow link in the respiratory band. GSC applied to spontaneous cardiovascular and cerebrovascular oscillations is a promising tool for describing and monitoring disturbances associated with posture modification.

Evaluation of cardiovascular and cerebrovascular control mechanisms in postural orthostatic tachycardia syndrome via conditional transfer entropy: the impact of the respiratory signal type.

Objective.Closed loop cardiovascular (CV) and cerebrovascular (CBV) variability interactions are assessed via transfer entropy (TE) from systolic arterial pressure (SAP) to heart period (HP) and vice versa and from mean arterial pressure (MAP) to mean cerebral blood velocity (MCBv) and vice versa. This analysis is exploited to assess the efficiency of baroreflex and cerebral autoregulation. This study aims at characterizing CV and CBV controls in postural orthostatic tachycardiac syndrome (POTS) subjects experiencing exaggerated sympathetic response during orthostatic challenge via unconditional TE and TE conditioned on respiratory activity (R).Approach.In 18 healthy controls (age: 28 ± 13 yrs; 5 males, 13 females) and 15 POTS individuals (age: 29 ± 11 yrs; 3 males, 12 females) we acquired beat-to-beat variability of HP, SAP, MAP and MCBv and twoRsignals, namely respiratory chest movement (RCM) and capnogram (CAP). Recordings were made at sitting rest and during active standing (STAND). TE was computed via vector autoregressive approach.Main results.We found that: (i) when assessing CV interactions, the increase of the TE from SAP to HP during STAND, indicating baroreflex activation, is detected solely when conditioning on RCM; (ii) when assessing CBV interactions, the impact ofRon the TE computation is negligible; (iii) POTS shows baroreflex impairment during STAND; (iv) POTS exhibits a normal CBV response to STAND.Significance.TE is useful for detecting the impairment of specific regulatory mechanisms in POTS. Moreover, using differentRsignals highlights the sensitivity of CV and CBV controls to specificRaspects.

On the Different Abilities of Cross-Sample Entropy and K-Nearest-Neighbor Cross-Unpredictability in Assessing Dynamic Cardiorespiratory and Cerebrovascular Interactions.

Nonlinear markers of coupling strength are often utilized to typify cardiorespiratory and cerebrovascular regulations. The computation of these indices requires techniques describing nonlinear interactions between respiration (R) and heart period (HP) and between mean arterial pressure (MAP) and mean cerebral blood velocity (MCBv). We compared two model-free methods for the assessment of dynamic HP-R and MCBv-MAP interactions, namely the cross-sample entropy (CSampEn) and k-nearest-neighbor cross-unpredictability (KNNCUP). Comparison was carried out first over simulations generated by linear and nonlinear unidirectional causal, bidirectional linear causal, and lag-zero linear noncausal models, and then over experimental data acquired from 19 subjects at supine rest during spontaneous breathing and controlled respiration at 10, 15, and 20 breaths·minute-1 as well as from 13 subjects at supine rest and during 60° head-up tilt. Linear markers were computed for comparison. We found that: (i) over simulations, CSampEn and KNNCUP exhibit different abilities in evaluating coupling strength; (ii) KNNCUP is more reliable than CSampEn when interactions occur according to a causal structure, while performances are similar in noncausal models; (iii) in healthy subjects, KNNCUP is more powerful in characterizing cardiorespiratory and cerebrovascular variability interactions than CSampEn and linear markers. We recommend KNNCUP for quantifying cardiorespiratory and cerebrovascular coupling.

Model-based spectral causality of cardiovascular variability interactions during head-down tilt.

Objective. Cardiovascular control mechanisms are commonly studied during baroreceptor unloading induced by head-up tilt. Conversely, the effect of a baroreceptor loading induced by head-down tilt (HDT) is less studied especially when the stimulus is of moderate intensity and using model-based spectral causality markers. Thus, this study computes model-based causality markers in the frequency domain derived via causal squared coherence and Geweke spectral causality approach from heart period (HP) and systolic arterial pressure (SAP) variability series.Approach. We recorded HP and SAP variability series in 12 healthy men (age: from 41 to 71 yrs, median: 57 yrs) during HDT at -25°. The approaches are compared by considering two different bivariate model structures, namely the autoregressive and dynamic adjustment models. Markers are computed in traditional frequency bands utilized in cardiovascular control analysis, namely the low frequency (LF, from 0.04 to 0.15 Hz) and high frequency (HF, from 0.15 to 0.4 Hz) bands.Main results. We found that: (i) the two spectral causality metrics are deterministically related but spectral causality markers exhibit different discriminative ability; (ii) HDT reduces the involvement of the baroreflex in regulating HP-SAP variability interactions in the LF band, while leaving unmodified the action of mechanical feedforward mechanisms in both LF and HF bands; (iii) this conclusion does not depend on the model structure.Significance. We conclude that HDT can be utilized to reduce the impact of baroreflex and to study the contribution of regulatory mechanisms different from baroreflex to the complexity of cardiovascular control in humans.

Changes of the cardiac baroreflex bandwidth during postural challenges.

Baroreflex is commonly typified from heart period (HP) and systolic arterial pressure (SAP) spontaneous variations in the frequency domain mainly by estimating its sensitivity. However, an informative parameter linked to the rapidity of the HP response to SAP changes, such as the baroreflex bandwidth, remains unquantified. We propose a model-based parametric approach for estimating the baroreflex bandwidth from the impulse response function (IRF) of the HP-SAP transfer function (TF). The approach accounts explicitly for the action of mechanisms modifying HP regardless of SAP changes. The method was tested during graded baroreceptor unloading induced by head-up tilt (HUT) at 15°, 30°, 45°, 60°, and 75° (T15, T30, T45, T60, and T75) in 17 healthy individuals (age: 21-36 yr; 9 females and 8 males) and during baroreceptor loading obtained via head-down tilt (HDT) at -25° in 13 healthy men (age: 41-71 yr). The bandwidth was estimated as the decay constant of the monoexponential IRF fitting. The method was robust because the monoexponential fitting described adequately the HP dynamics following an impulse of SAP. We observed that 1) baroreflex bandwidth is reduced during graded HUT and this narrowing is accompanied by the reduction of the bandwidth of mechanisms that modify HP regardless of SAP changes and 2) baroreflex bandwidth is not affected by HDT but that of SAP-unrelated mechanisms becomes wider. This study provides a method for estimating a baroreflex feature that provides different information compared with the more usual baroreflex sensitivity while accounting explicitly for the action of mechanisms changing HP irrespective of SAP.

Cardiorespiratory coupling in mechanically ventilated patients studied via synchrogram analysis.

Respiration and cardiac activity are strictly interconnected with reciprocal influences. They act as weakly coupled oscillators showing varying degrees of phase synchronization and their interactions are affected by mechanical ventilation. The study aims at differentiating the impact of three ventilatory modes on the cardiorespiratory phase coupling in critically ill patients. The coupling between respiration and heartbeat was studied through cardiorespiratory phase synchronization analysis carried out via synchrogram during pressure control ventilation (PCV), pressure support ventilation (PSV), and neurally adjusted ventilatory assist (NAVA) in critically ill patients. Twenty patients were studied under all the three ventilatory modes. Cardiorespiratory phase synchronization changed significantly across ventilatory modes. The highest synchronization degree was found during PCV session, while the lowest one with NAVA. The percentage of all epochs featuring synchronization regardless of the phase locking ratio was higher with PCV (median: 33.9%, first-third quartile: 21.3-39.3) than PSV (median: 15.7%; first-third quartile: 10.9-27.8) and NAVA (median: 3.7%; first-third quartile: 3.3-19.2). PCV induces a significant amount of cardiorespiratory phase synchronization in critically ill mechanically ventilated patients. Synchronization induced by patient-driven ventilatory modes was weaker, reaching the minimum with NAVA. Findings can be explained as a result of the more regular and powerful solicitation of the cardiorespiratory system induced by PCV. The degree of phase synchronization between cardiac and respiratory activities in mechanically ventilated humans depends on the ventilatory mode.

Comparing Cross-Sample Entropy and K-Nearest-Neighbor Cross-Predictability Approaches for the Evaluation of Cardiorespiratory and Cerebrovascular Dynamic Interactions.

Quantification of the cardiorespiratory and cerebrovascular couplings is a relevant clinical issue given that their changes are considered signs of pathological status. The inherent nonlinearity of mechanisms underlying cardiorespiratory and cerebrovascular links requires nonlinear tools for their reliable evaluation. In the present study we compare two nonlinear methods for the assessment of coupling strength between two time series, namely cross-sample entropy (CSampEn) and k-nearest-neighbor cross-predictability (KNNCP). CSampEn uses a strategy that fixes the pattern length, while KNNCP optimizes the pattern length to maximize cross-predictability. CSampEn and KNNCP were applied to the beat-to-beat series of heart period (HP) and respiration (R) during a controlled breathing protocol with the aim at assessing cardiorespiratory coupling and to the beat-to-beat series of mean cerebral blood flow (MCBF) and mean arterial pressure (MAP) during an orthostatic stressor with the aim at evaluating cerebrovascular coupling. Although both the methods have the possibility to quantify the degree of HP-R and MCBF-MAP association, they exhibited different statistical power and even diverse trends in response to the considered physiological challenges. CSampEn and KNNCP are not interchangeable and should be utilized in association more than in alternative for the quantification of the HP-R and MCBF-MAP coupling strength. Clinical Relevance - This study proves that cross-entropy and cross-predictability might lead to different conclusions about cardiorespiratory and cerebrovascular couplings.

Spectral decomposition of cerebrovascular and cardiovascular interactions in patients prone to postural syncope and healthy controls.

We present a framework for the linear parametric analysis of pairwise interactions in bivariate time series in the time and frequency domains, which allows the evaluation of total, causal and instantaneous interactions and connects time- and frequency-domain measures. The framework is applied to physiological time series to investigate the cerebrovascular regulation from the variability of mean cerebral blood flow velocity (CBFV) and mean arterial pressure (MAP), and the cardiovascular regulation from the variability of heart period (HP) and systolic arterial pressure (SAP). We analyze time series acquired at rest and during the early and late phase of head-up tilt in subjects developing orthostatic syncope in response to prolonged postural stress, and in healthy controls. The spectral measures of total, causal and instantaneous coupling between HP and SAP, and between MAP and CBFV, are averaged in the low-frequency band of the spectrum to focus on specific rhythms, and over all frequencies to get time-domain measures. The analysis of cardiovascular interactions indicates that postural stress induces baroreflex involvement, and its prolongation induces baroreflex dysregulation in syncope subjects. The analysis of cerebrovascular interactions indicates that the postural stress enhances the total coupling between MAP and CBFV, and challenges cerebral autoregulation in syncope subjects, while the strong sympathetic activation elicited by prolonged postural stress in healthy controls may determine an increased coupling from CBFV to MAP during late tilt. These results document that the combination of time-domain and spectral measures allows us to obtain an integrated view of cardiovascular and cerebrovascular regulation in healthy and diseased subjects.

Exploring metrics for the characterization of the cerebral autoregulation during head-up tilt and propofol general anesthesia.

Techniques grounded on the simultaneous utilization of Tiecks' second order differential equations and spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV), recorded from middle cerebral arteries through a transcranial Doppler device, provide a characterization of cerebral autoregulation (CA) via the autoregulation index (ARI). These methods exploit two metrics for comparing the measured MCBFV series with the version predicted by Tiecks' model: normalized mean square prediction error (NMSPE) and normalized correlation ρ. The aim of this study is to assess the two metrics for ARI computation in 13 healthy subjects (age: 27 ± 8 yrs., 5 males) at rest in supine position (REST) and during 60° head-up tilt (HUT) and in 19 patients (age: 64 ± 8 yrs., all males), scheduled for coronary artery bypass grafting, before (PRE) and after (POST) propofol general anesthesia induction. Analyses were carried out over the original MAP and MCBFV pairs and surrogate unmatched couples built individually via time-shifting procedure. We found that: i) NMSPE and ρ metrics exhibited similar performances in passing individual surrogate test; ii) the two metrics could lead to different ARI estimates; iii) CA was not different during HUT or POST compared to baseline and this conclusion held regardless of the technique and metric for ARI estimation. Results suggest a limited impact of the sympathetic control on CA.

Cardiorespiratory coupling strength in athletes and non-athletes.

PURPOSE: Despite the relevant presence of nonlinear components on heart period (HP) likely due to cardiorespiratory coupling (CRC), the HP is frequently analyzed in absence of concomitant recordings of respiratory movements (RESP). This study aims to assess the cardiovascular dynamics and CRC during postural challenge in athletes and non-athletes via joint symbolic analysis (JSA). METHODS: A cross-sectional study was conducted in 50 men, aged between 20 and 40 yrs, divided into athletes (n = 25) and non-athletes (n = 25) groups. The electrocardiogram, blood pressure and RESP signals were recorded during 15 min in both supine position (REST) and after active postural maneuver (STAND). From the beat-to-beat series of HP, systolic arterial pressure (SAP) and RESP, we computed the time and frequency domain indexes and baroreflex sensitivity. The JSA was based on the definition of symbolic HP and RESP patterns and on the evaluation of the rate of their simultaneous occurrence in both HP and RESP series. RESULTS: The JSA analysis was able to identify higher CRC strength at REST in athletes. Moreover, the response of CRC to STAND depended on the time scales of the analysis and was much more evident in athletes than in non-athletes, thus indicating a more reactive autonomic control in athletes. CONCLUSION: Assessing CRC in athletes via JSA provides additional information compared to standard linear time and frequency domain tools likely due to the more relevant presence of nonlinearities in HP-RESP variability relationship.