Respiratory Sinus Arrhythmia Mechanisms in Young Obese Subjects

Autonomic nervous system (ANS) activity and imbalance between its sympathetic and parasympathetic components are important factors contributing to the initiation and progression of many cardiovascular disorders related to obesity. The results on respiratory sinus arrhythmia (RSA) magnitude changes as a parasympathetic index were not straightforward in previous studies on young obese subjects. Considering the potentially unbalanced ANS regulation with impaired parasympathetic control in obese patients, the aim of this study was to compare the relative contribution of baroreflex and non-baroreflex (central) mechanisms to the origin of RSA in obese vs. control subjects. To this end, we applied a recently proposed information-theoretic methodology – partial information decomposition (PID) – to the time series of heart rate variability (HRV, computed from RR intervals in the ECG), systolic blood pressure (SBP) variability, and respiration (RESP) pattern measured in 29 obese and 29 ageand gender-matched non-obese adolescents and young adults monitored in the resting supine position and during postural and cognitive stress evoked by head-up tilt and mental arithmetic. PID was used to quantify the so-called unique information transferred from RESP to HRV and from SBP to HRV, reflecting, respectively, non-baroreflex and RESP-unrelated baroreflex HRV mechanisms, and the redundant information transferred from (RESP, SBP) to HRV, reflecting RESP-related baroreflex RSA mechanisms. Our results suggest that obesity is associated: (i) with blunted involvement of non-baroreflex RSA mechanisms, documented by the lower unique information transferred from RESP to HRV at rest; and (ii) with a reduced response to postural stress (but not to mental stress), documented by the lack of changes in the unique information transferred from RESP and SBP to HRV in obese subjects moving from supine to upright, and by a decreased redundant information transfer in obese compared to controls in the upright position. These findings were observed in the presence of an unchanged RSA magnitude measured as the high frequency (HF) power of HRV, thus suggesting that the changes in ANS imbalance related to obesity in adolescents and young adults are subtle and can be revealed by dissecting RSA mechanisms into its components during various challenges

HUMAN CARDIOVASCULAR RESPONSES TO SIMULATED PARTIAL GRAVITY AND A SHORT HYPERGRAVITY EXPOSURE

Orthostatic intolerance (OI), i.e., the inability to maintain stable arterial pressure during upright posture, is a major problem for astronauts after spaceflight. Therefore, one important goal of spaceflight-related research is the development of countermeasures to prevent post flight OI. Given the rarity and expense of spaceflight, countermeasure development requires ground-based simulations of partial gravity to induce appropriate orthostatic effects on the human body, and to test the efficacy of potential countermeasures. To test the efficacy of upright lower body positive pressure (LBPP) as a model for simulating cardiovascular responses to lunar and Martian gravities on Earth, cardiovascular responses to upright LBPP were compared with those of head-up tilt (HUT), a well-accepted simulation of partial gravity, in both ambulatory and cardiovascularly deconditioned subjects. Results indicate that upright LBPP and HUT induced similar changes in cardiovascular regulation, supporting the use of upright LBPP as a potential model for simulating cardiovascular responses to standing and moving in lunar and Martian gravities. To test the efficacy of a short exposure to artificial gravity (AG) as a countermeasure to spaceflight-induced OI, orthostatic tolerance limits (OTL) and cardiovascular responses to orthostatic stress were tested in cardiovascularly deconditioned subjects, using combined 70º head-up tilt and progressively increased lower body negative pressure, once following 90 minutes AG exposure and once following 90 minutes of -6º head-down bed rest (HDBR). Results indicate that a short AG exposure increased OTL of cardiovascularly deconditioned subjects, with increased baroreflex and sympathetic responsiveness, compared to those measured after HDBR exposure. To gain more insight into mechanisms of causal connectivity in cardiovascular and cardiorespiratory oscillations during orthostatic challenge in both ambulatory and cardiovascularly deconditioned subjects, couplings among R-R intervals (RRI), systolic blood pressure (SBP) and respiratory oscillations in response to graded HUT and dehydration were studied using a phase synchronization approach. Results indicate that increasing orthostatic stress disassociated interactions among RRI, SBP and respiration, and that dehydration exacerbated the disconnection. The loss of causality from SBP to RRI following dehydration suggests that dehydration also reduced involvement of baroreflex regulation, which may contribute to the increased occurrence of OI

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

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

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

Measuring the Rate of Information Exchange in Point-Process Data With Application to Cardiovascular Variability

The amount of information exchanged per unit of time between two dynamic processes is an important concept for the analysis of complex systems. Theoretical formulations and data-efficient estimators have been recently introduced for this quantity, known as the mutual information rate (MIR), allowing its continuous-time computation for event-based data sets measured as realizations of coupled point processes. This work presents the implementation of MIR for point process applications in Network Physiology and cardiovascular variability, which typically feature short and noisy experimental time series. We assess the bias of MIR estimated for uncoupled point processes in the frame of surrogate data, and we compensate it by introducing a corrected MIR (cMIR) measure designed to return zero values when the two processes do not exchange information. The method is first tested extensively in synthetic point processes including a physiologically-based model of the heartbeat dynamics and the blood pressure propagation times, where we show the ability of cMIR to compensate the negative bias of MIR and return statistically significant values even for weakly coupled processes. The method is then assessed in real point-process data measured from healthy subjects during different physiological conditions, showing that cMIR between heartbeat and pressure propagation times increases significantly during postural stress, though not during mental stress. These results document that cMIR reflects physiological mechanisms of cardiovascular variability related to the joint neural autonomic modulation of heart rate and arterial compliance

Skeletal Muscle Pump Drives Control of Cardiovascular and Postural Systems

The causal interaction between cardio-postural-musculoskeletal systems is critical in maintaining postural stability under orthostatic challenge. The absence or reduction of such interactions could lead to fainting and falls often experienced by elderly individuals. The causal relationship between systolic blood pressure (SBP), calf electromyography (EMG), and resultant center of pressure (COPr) can quantify the behavior of cardio-postural control loop. Convergent cross mapping (CCM) is a non-linear approach to establish causality, thus, expected to decipher nonlinear causal cardio-postural-musculoskeletal interactions. Data were acquired simultaneously from young participants (25 ± 2 years, n = 18) during a 10-minute sit-to-stand test. In the young population, skeletal muscle pump was found to drive blood pressure control (EMG → SBP) as well as control the postural sway (EMG → COPr) through the significantly higher causal drive in the direction towards SBP and COPr. Furthermore, the effect of aging on muscle pump activation associated with blood pressure regulation was explored. Simultaneous EMG and SBP were acquired from elderly group (69 ± 4 years, n = 14). A significant (p = 0.002) decline in EMG → SBP causality was observed in the elderly group, compared to the young group. The results highlight the potential of causality to detect alteration in blood pressure regulation with age, thus, a potential clinical utility towards detection of fall proneness

Association between autonomic control indexes and mortality in subjects admitted to intensive care unit

This study checks whether autonomic markers derived from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) and from their interactions with spontaneous or mechanical respiration (R) are associated with mortality in patients admitted to intensive care unit (ICU). Three-hundred consecutive HP, SAP and R values were recorded during the first day in ICU in 123 patients. Population was divided into survivors (SURVs, n = 83) and non-survivors (NonSURVs, n = 40) according to the outcome. SURVs and NonSURVs were aged-and gender-matched. All subjects underwent modified head-up tilt (MHUT) by tilting the bed back rest segment to 60 degrees. Autonomic control indexes were computed using time-domain, spectral, cross-spectral, complexity, symbolic and causality techniques via univariate, bivariate and conditional approaches. SAP indexes derived from time-domain, model-free complexity and symbolic approaches were associated with the endpoint, while none of HP variability markers was. The association was more powerful during MHUT. Linear cross-spectral and causality indexes were useless to separate SURVs from NonSURVs, while nonlinear bivariate symbolic markers were successful. When indexes were combined with clinical scores, only SAP variance provided complementary information. Cardiovascular control variability indexes, especially when derived after an autonomic challenge such as MHUT, can improve mortality risk stratification in ICU

Disentangling cardiovascular control mechanisms during head-down tilt via joint transfer entropy and self-entropy decompositions

A full decomposition of the predictive entropy (PE) of the spontaneous variations of the heart period (HP) given systolic arterial pressure (SAP) and respiration (R) is proposed. The PE of HP is decomposed into the joint transfer entropy (JTE) from SAP and R to HP and self-entropy (SE) of HP. The SE is the sum of three terms quantifying the synergistic/redundant contributions of HP and SAP, when taken individually and jointly, to SE and one term conditioned on HP and SAP denoted as the conditional SE (CSE) of HP given SAP and R. The JTE from SAP and R to HP is the sum of two terms attributable to SAP or R plus an extra term describing the redundant/synergistic contribution to the JTE. All quantities were computed during cardiopulmonary loading induced by -25\uc2\ub0 head-down tilt (HDT) via a multivariate linear regression approach. We found that: (i) the PE of HP decreases during HDT; (ii) the decrease of PE is attributable to a lessening of SE of HP, while the JTE from SAP and R to HP remains constant; (iii) the SE of HP is dominant over the JTE from SAP and R to HP and the CSE of HP given SAP and R is prevailing over the SE of HP due to SAP and R both in supine position and during HDT; (iv) all terms of the decompositions of JTE from SAP and R to HP and SE of HP due to SAP and R were not affected by HDT; (v) the decrease of the SE of HP during HDT was attributed to the reduction of the CSE of HP given SAP and R; (vi) redundancy of SAP and R is prevailing over synergy in the information transferred into HP both in supine position and during HDT, while in the HP information storage synergy and redundancy are more balanced. The approach suggests that the larger complexity of the cardiac control during HDT is unrelated to the baroreflex control and cardiopulmonary reflexes and may be related to central commands and/or modifications of the dynamical properties of the sinus node

Parasympathetic-sympathetic causal interactions assessed by time-varying multivariate autoregressive modeling of electrodermal activity and heart-rate-variability

Objective: Most of the bodily functions are regulated by multiple interactions between the parasympathetic (PNS) and sympathetic (SNS) nervous system. In this study, we propose a novel framework to quantify the causal flow of information between PNS and SNS through the analysis of heart rate variability (HRV) and electrodermal activity (EDA) signals. Methods: Our method is based on a time-varying (TV) multivariate autoregressive model of EDA and HRV time-series and incorporates physiologically inspired assumptions by estimating the Directed Coherence in a specific frequency range. The statistical significance of the observed interactions is assessed by a bootstrap procedure purposely developed to infer causalities in the presence of both TV model coefficients and TV model residuals (i.e., heteroskedasticity). We tested our method on two different experiments designed to trigger a sympathetic response, i.e., a hand-grip task (HG) and a mental-computation task (MC). Results: Our results show a parasympathetic driven interaction in the resting state, which is consistent across different studies. The onset of the stressful stimulation triggers a cascade of events characterized by the presence or absence of the PNS-SNS interaction and changes in the directionality. Despite similarities between the results related to the two tasks, we reveal differences in the dynamics of the PNS-SNS interaction, which might reflect different regulatory mechanisms associated with different stressors. Conclusion: We estimate causal coupling between PNS and SNS through MVAR modeling of EDA and HRV time-series. Significance: Our results suggest promising future applicability to investigate more complex contexts such as affective and pathological scenarios

Aerospace medicine and biology: A cumulative index to the continuing bibliography of the 1973 issues

A cumulative index to the abstracts contained in Supplements 112 through 123 of Aerospace Medicine and Biology A Continuing Bibliography is presented. It includes three indexes: subject, personal author, and corporate source