Systolic Arterial Pressure Variability Research Articles

Insulin Treatment Does Not Prevent EARLY Autonomic Cardiovascular and Diastolic Dysfunctions in Streptozotocin-Induced Diabetic Rats.

Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk.

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.

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.

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.Graphical

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 two R signals, 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 of R on 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 different R signals highlights the sensitivity of CV and CBV controls to specific R aspects.

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.

Hypertension, Blood Pressure Variability, and Acute Kidney Injury in Hospitalized Children.

Background Although hypertensive blood pressure measurements are common in hospitalized children, the degree of inpatient hypertension and blood pressure variability (BPV) associated with end organ complications like acute kidney injury (AKI) is unknown. Methods and Results All analyses are based on a retrospective cohort of children aged 1 to 17 years with ≥2 creatinine measurements during admission from 2014 to 2018. We used time-updated Cox models to evaluate the association between BPV and hypertension with AKI. Time-varying BPV and hypertension were based on blood pressure in the preceding 72 hours. For the analysis of hypertension and AKI, we excluded patients on vasopressors to ensure comparison between hypertensive and normotensive patients. During 5425 pediatric encounters, 258 430 blood pressure measurements were recorded (median [interquartile range] 22 [11-47] readings per encounter). Among all measurements, 32.7% were ≥95th percentile and 18.9% were ≥99th percentile for age, sex, and height. AKI occurred in 389 (7.2%) encounters. We observed a U-shaped relationship between mean blood pressure and incident AKI. BPV was associated with AKI, with the largest effect sizes in the systolic and mean arterial pressure variability measures. Multiple hypertension thresholds were associated with AKI after controlling for confounders. In an additional multivariable model adjusted for BPV, the association between hypertension and AKI was attenuated but remained significant for hypertension defined as three stage 2 measurements in 1 day (hazard ratio, 1.43 [95% CI, 1.01-2.01]). Conclusions Hypertension and BPV are associated with AKI in hospitalized children. Future studies are needed to determine how pharmacologic and nonpharmacologic interventions modify AKI risk in pediatric inpatients with hypertension.

Short exposure to high salt in drinking solution leads to a cardiovascular phenotype of hypertension without changes in the blood volume of rats.

What is the central question of this study? Is the cardiovascular phenotype of high blood pressure observed in rats salt loaded with 2% NaCl in drinking solution a blood volume-dependent hypertension? What is the main finding and its importance? Animals exposed to 2% NaCl drinking solution develop hypertension, with dominance of sympathetic outflow and high [Na+ ] in the cerebrospinal fluid, but without changes in the blood volume. The phenotype of salt-dependent hypertension might be related to accumulation of [Na+ ] in the cerebrospinal fluid, which makes it an interesting animal model in which to study the neuronal pathways involved in control of the circulation in osmotic challenge conditions. Evidence suggests that hypertension induced by high salt intake is correlated with an autonomic imbalance that favours sympathetic hyperactivity and an increase in vascular resistance, indicating a neurogenic component to this pathology. Although there are several animal models in which to study salt-induced hypertension with prolonged exposure to a high-sodium diet, here we sought to investigate whether the increase in arterial blood pressure of rats subjected to a short exposure to high salt, with 2% NaCl drinking solution instead of water, relies on changes in the circulating blood volume. Male Wistar rats were divided randomly into three groups: euhydrated (EU, n=10), salt loaded (SL, n=13) and water deprived (WD, n=6). The SL rats exhibited a significant increase in mean arterial blood pressure, with a large low-frequency component of systolic arterial blood pressure variability, when compared with the EU group. Circulating blood volume did not differ between SL and EU rats, but it was lower in WD rats. Compared with EU rats, the [Na+ ] in cerebrospinal fluid was higher in SL rats and similar in magnitude to the WD rats. Plasma [Na+ ] did not differ between SL and EU rats, but it was higher in WD rats. Collectively, our data suggest that the hypertension induced by a short exposure to high salt intake closely resembles a neurogenic mechanism, but not a blood volume-dependent mechanism, with cumulative [Na+ ] in the cerebrospinal fluid that could be associated with changes in the neurochemistry of autonomic nuclei, which are highly susceptible to osmotic stress related to high salt consumption.

Odnos varijabilnosti arterijskog pritiska iz ambulatornog 24-časovnog monitoringa arterijskog pritiska sa ehokardiografskim parametrima u bolesnika pod antihipertenzivnom terapijom

Introduction: Variability of systolic daytime arterial pressure was until recently a controversial parameter but is now recognized as an independent prognostic risk factor for stroke in hypertensive patients. Blood pressure variability is a quantitative index of spontaneous daily and nocturnal variations in systolic and diastolic arterial blood pressure and has been proposed as a risk factor for inducing subclinical damage to target organs in arterial hypertension. Besides varying degrees of left ventricular myocardial hypertrophy (LVH), patients with hypertension also exhibit accompanying diastolic dysfunction of the left ventricle as an early sign of hypertensive damage, even when myocardial hypertrophy does not develop. The variability of pressure over 24 hours in Ambulatory Blood Pressure Monitoring (ABPM) has not been sufficiently studied in terms of correlation with echocardiographic parameters in controlled hypertension. Methods: A total of 196 adequately treated patients with stage 2 hypertension, with a target of achieving normotension less than 140/90, were examined. The total of 196 patients, 109 males and 87 females, with a mean age of 49.3 ± 8.4 years, untreated or inadequately treated patients with stage 2 hypertension (mean BP before treatment 167/106 mmHg) were divided into three groups according to blood pressure variability parameters. Alongside standard methods: medical history, clinical examination, and electrocardiogram (ECG), 24-hour ambulatory arterial pressure monitoring (ABPM, so-called blood pressure holter) was performed with 24-hour, daytime, and nighttime variability of systolic and diastolic blood pressure as well as Color and Tissue Doppler echocardiography after adequate treatment. Results: Elevated blood pressure variability was observed in 66/196 patients (34%) in group V despite good pressure regulation, while 130/169 (66%) had normal variability - group C (control). A subgroup ExtV was particularly highlighted within group V with extreme variability of daytime systolic BP (SD>20 mmHg) - 15/66 patients (8%). Evaluation of left ventricular myocardial mass index (LVMI) showed no difference in the degree of LVH between groups C and V. In the subgroup ExtV (from group V with extreme blood pressure variability), comprising 15/66 patients (8%), a significant difference in the degree of left ventricular myocardial hypertrophy was found between groups C and V regarding extreme variability (p<0.01). There was no difference concerning gender and age structure. Statistical analysis of investigated 24-hour blood pressure parameters and echocardiographic parameters did not show significant correlation through calculation of the linear correlation coefficient between mean arterial pressure measured by 24-hour ambulatory pressure monitoring and standard deviations of daytime and nighttime pressure and the degree of left ventricular myocardial hypertrophy (linear correlation coefficients r <0.20), as expected. However, there is a moderate but significant correlation between the best echocardiographic parameter of diastolic function, E/E' ratio, and variability of daytime systolic pressure: r= 0.41. Only the subgroup with extreme variability ExtV in terms of daytime systolic pressure has a statistically significant correlation with the degree of LVMI myocardial hypertrophy, r=0.51. Conclusion: One-third of the examined patients, 66/196 patients (34%) in group V, had elevated blood pressure variability despite good pressure regulation. There was no significant difference in the degree of left ventricular myocardial hypertrophy between the investigated parameters of 24-hour blood pressure and echocardiographic indices, except in extreme variability ExtV (P<0.01). However, there is a moderate but significant correlation between the best echocardiographic parameter of diastolic function, E/E' ratio, and variability of daytime systolic pressure: r= 0.41. Only the subgroup with extreme variability ExtV in terms of daytime systolic pressure has a statistically significant correlation with the degree of LVMI myocardial hypertrophy, r=0.51.

Feasibility of Ultra-Short-Term Analysis of Heart Rate and Systolic Arterial Pressure Variability at Rest and during Stress via Time-Domain and Entropy-Based Measures

Heart Rate Variability (HRV) and Blood Pressure Variability (BPV) are widely employed tools for characterizing the complex behavior of cardiovascular dynamics. Usually, HRV and BPV analyses are carried out through short-term (ST) measurements, which exploit ~five-minute-long recordings. Recent research efforts are focused on reducing the time series length, assessing whether and to what extent Ultra-Short-Term (UST) analysis is capable of extracting information about cardiovascular variability from very short recordings. In this work, we compare ST and UST measures computed on electrocardiographic R-R intervals and systolic arterial pressure time series obtained at rest and during both postural and mental stress. Standard time-domain indices are computed, together with entropy-based measures able to assess the regularity and complexity of cardiovascular dynamics, on time series lasting down to 60 samples, employing either a faster linear parametric estimator or a more reliable but time-consuming model-free method based on nearest neighbor estimates. Our results are evidence that shorter time series down to 120 samples still exhibit an acceptable agreement with the ST reference and can also be exploited to discriminate between stress and rest. Moreover, despite neglecting nonlinearities inherent to short-term cardiovascular dynamics, the faster linear estimator is still capable of detecting differences among the conditions, thus resulting in its suitability to be implemented on wearable devices.

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.

Dampak Accrual Basic dan Sistem Pengendalian Intern Pemerintah terhadap Akuntabilitas kinerja Instansi Pemerintah

Researchers tested whether the application of accrual-based government accounting standards (SAP) as a form of GCG was able to improve the performance of government agencies KESBANGPOL through accrual-based SAP variables and a good internal control system was expected to be able to realize good governance. This study uses nine variables. Researchers distributed questionnaires to 47 employees of Kesbangpol Banjarmasin and tested the data through multiple regression analysis. The results showed that the accrual-based SAP implementation variables had an effect, and human resources, risk management, and supervision had a positive effect on AKIP. Variables of organizational commitment, information technology, control environment, control activities, information, and communication do not affect AKIP.

Dynamic cerebrovascular autoregulation in patients prone to postural syncope: Comparison of techniques assessing the autoregulation index from spontaneous variability series.

Three approaches to the assessment of cerebrovascular autoregulation (CA) via the computation of the autoregulation index (ARI) from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) were applied: 1) a time domain method (TDM); 2) a nonparametric method (nonPM); 3) a parametric method (PM). Performances were tested over matched and surrogate unmatched pairs. Data were analyzed at supine resting (REST) and during the early phase of 60° head-up tilt (TILT) in 13 subjects with previous history of postural syncope (SYNC, age: 28±9yrs.; 5 males) and 13 control individuals (noSYNC, age: 27±8yrs.; 5 males). Analysis was completed by computing autonomic markers from heart period (HP) and systolic arterial pressure (SAP) variability series via spectral approach. HP and SAP spectral indexes suggested that noSYNC and SYNC groups exhibited different autonomic responses to TILT. ARI analysis indicated that: i) all methods have a sufficient statistical power to separate matched from unmatched pairs with the exception of nonPM applied to impulse response; ii) ARI estimates derived from different methods might be uncorrelated and, even when correlated, might exhibit a significant bias; iii) orthostatic stressor did not induce any evident ARI change in either noSYNC or SYNC individuals; iv) this conclusion held regardless of the method. Methods for the ARI estimation from spontaneous variability provide different ARIs but none indicate that noSYNC and SYNC subjects have different dynamic component of CA.

Relationships Between Cardiovascular Autonomic Profile and Work Ability in Patients With Pure Autonomic Failure.

Pure autonomic failure (PAF) is a rare disorder belonging to the group of synucleinopathies, characterized by autonomic nervous system degeneration. Severe orthostatic intolerance with recurrent syncope while standing are the two most disabling manifestations. Symptoms may start at middle age, thus affecting people at their working age. The aims of this study were to evaluate the autonomic and work ability impairment of a group of PAF patients and assess the relationships between cardiovascular autonomic control and work ability in these patients. Eleven PAF patients (age 57.3 ± 6.7 years), engaged in work activity, participated in the study. They completed the Composite Autonomic Symptom Score (COMPASS-31, range 0 no symptom-100 maximum symptom intensity) and Work Ability questionnaires (Work Ability Index, WAI, range 7–49; higher values indicate better work ability and lower values indicating unsatisfactory or jeopardized work ability). Electrocardiogram, blood pressure and respiratory activity were continuously recorded for 10 min while supine and during 75° head-up tilt (HUT). Autoregressive spectral analysis of cardiac cycle length approximated as the time distance between two consecutive R-wave peaks (RR) and systolic arterial pressure (SAP) variabilities provided the power in the high frequency (HF, 0.15–0.40 Hz) and low frequency (LF, 0.04–0.15 Hz) bands of RR and SAP variabilities. Cardiac sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF), while the LF power of SAP (LFSAP) quantified the vascular sympathetic modulation. Changes in cardiovascular autonomic indexes induced by HUT were calculated as the delta (Δ) between HUT and supine resting positions. Spearman correlation analysis was applied. PAF patients were characterized by a moderate autonomic dysfunction (COMPASS-31 total score 47.08 ± 20.2) and by a reduction of work ability (WAI 26.88 ± 10.72). Direct significant correlations were found between WAI and ΔLFRR (r = 0.66, p = 0.03) and ΔLF/HFRR (r = 0.70, p = 0.02). Results indicate that patients who were better able to modulate heart rate, as revealed by a greater cardiac sympathetic increase and/or vagal withdrawal during the orthostatic stimulus, were those who reported higher values of WAI. This finding could be relevant to propose new strategies in the occupational environment to prevent early retirement or to extend the working life of these patients.

Variability of arterial pressure and cardiac rhythm in patients with coronary heart disease and diabetes mellitus: Effect of sodium-glucose co-transporter 2 inhibitor

Introduction: A factor that worsens the course of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (DM2) is cardiovascular autonomic neuropathy (CAN), in which the risk of sudden death increases fivefold. The prevalence of CAN in patients with both CHD and DM2 may reach 60%. Classic cardiovascular tests (CCT) do not permit identification of CAN at the preclinical stage. A modern method of treatment for DM2 uses sodium-glucose co-transporter 2 inhibitors, which have confirmed cardioprotective effects.
 Aim: To analyze the prevalence of alterations of arterial pressure variability (APV) and of heart rhythm variability (HRV) in patients with both CHD and DM2 and the effect of empagliflozin on these parameters.
 Materials and methods: A total of 210 patients aged 64.5 6.7 years (103 men) with both CHD and DM2 were examined (group1). Anthropometric and biochemical parameters were analyzed, electrocardiogram and arterial pressure were monitored daily, and CCT was performed. For comparison, 64 patients with CHD with no alterations in the carbohydrate metabolism were examined (group2, n=64, aged 66.4 2.3 years). Further, among patients in group1, patients with impaired HRV and APV were selected, but they had CCT scores 4.0, and they were divided into group1G (n=22) where empagliflozin was added (1025 mg/day) and group1C (n=20) where the previous therapy was continued.
 Results: CAN was detected in 22% of patients with CHD and DM2, and all patients had impaired HRV and ADV. Deviations of HRV and APV parameters with normal CCT scores ( 4.0) were detected in 43% of the patients. Within 6 months of treatment with empagliflozin, the HbA1c level decreased from 8.38% 0.56% to 6.9% 0.26% (p 0.05); in the groupwithout empagliflozin treatment, it decreased from 8.28% 0.32% to 7.30% 0.29% (p 0.05). In the empagliflozin group, the average heart rate per day decreased from 86.7 2.4 to 76.7 2.1 beats/min (p 0.05), the circadian index increased from 1.19 0.02 to 1.30 0.01 (p 0.05), the SDNN increased from 106.1 2.21 to 114.03 2.34 ms (p 0.05), and the systolic arterial pressure variability index decreased from 22.9% 1.7% to 16.4% 1.9% at daytime (p 0.05) and from 16.8% 2.2% to 12.3% 2.6% at nighttime (p 0.05).
 Conclusion: The identified alterations of HRV and APV parameters may be manifestations of CAN, and CCT score 4.0 may indicate the preclinical stage. Positive dynamics of HRV and APV was recorded with empagliflozin therapy, which improved the functional condition of the autonomic nervous system.

Acute autonomic effects of rose oxide on cardiovascular parameters of Wistar and spontaneously hypertensive rats

AimsAnti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR). MethodsRats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10–10 to 10–4 M) on aortic rings of rats were also assessed. Key findingsIn Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only). SignificanceRose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.

Information decomposition in the frequency domain: a new framework to study cardiovascular and cardiorespiratory oscillations.

While cross-spectral and information-theoretic approaches are widely used for the multivariate analysis of physiological time series, their combined utilization is far less developed in the literature. This study introduces a framework for the spectral decomposition of multivariate information measures, which provides frequency-specific quantifications of the information shared between a target and two source time series and of its expansion into amounts related to how the sources contribute to the target dynamics with unique, redundant and synergistic information. The framework is illustrated in simulations of linearly interacting stochastic processes, showing how it allows us to retrieve amounts of information shared by the processes within specific frequency bands which are otherwise not detectable by time-domain information measures, as well as coupling features which are not detectable by spectral measures. Then, it is applied to the time series of heart period, systolic and diastolic arterial pressure and respiration variability measured in healthy subjects monitored in the resting supine position and during head-up tilt. We show that the spectral measures of unique, redundant and synergistic information shared by these variability series, integrated within specific frequency bands of physiological interest and reflect the mechanisms of short-term regulation of cardiovascular and cardiorespiratory oscillations and their alterations induced by the postural stress. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Effects of Algorithmic Music on the Cardiovascular Neural Control.

Music influences many physiological parameters, including some cardiovascular (CV) control indices. The complexity and heterogeneity of musical stimuli, the integrated response within the brain and the limited availability of quantitative methods for non-invasive assessment of the autonomic function are the main reasons for the scarcity of studies about the impact of music on CV control. This study aims to investigate the effects of listening to algorithmic music on the CV regulation of healthy subjects by means of the spectral analysis of heart period, approximated as the time distance between two consecutive R-wave peaks (RR), and systolic arterial pressure (SAP) variability. We studied 10 healthy volunteers (age 39 ± 6 years, 5 females) both while supine (REST) and during passive orthostatism (TILT). Activating and relaxing algorithmic music tracks were used to produce possible contrasting effects. At baseline, the group featured normal indices of CV sympathovagal modulation both at REST and during TILT. Compared to baseline, at REST, listening to both musical stimuli did not affect time and frequency domain markers of both SAP and RR, except for a significant increase in mean RR. A physiological TILT response was maintained while listening to both musical tracks in terms of time and frequency domain markers, compared to baseline, an increase in mean RR was again observed. In healthy subjects featuring a normal CV neural profile at baseline, algorithmic music reduced the heart rate, a potentially favorable effect. The innovative music approach of this study encourages further research, as in the presence of several diseases, such as ischemic heart disease, hypertension, and heart failure, a standardized musical stimulation could play a therapeutic role.

Abstract 32: Exercise Training Corrects Blood-brain Barrier Dysfunction Within Preautonomic Areas Of Spontaneously Hypertensive Rats By Normalizing The Augmented Transcytosis

Introduction: Besides intense neuro-hormonal activation, hypertension is accompanied by blood-brain barrier (BBB) dysfunction within preautonomic areas and marked autonomic imbalance. We showed previously that exercise training (T) corrected both increased BBB leakage and autonomic dysfunction. There is no information on the mechanism(s) conditioning the normalization of BBB function Hypothesis: We hypothesized that T could modify the transcytosis and/or the paracellular transport across the capillary endothelium Methods: SHR and Wistar rats allocated to T (55% maximal capacity) or sedentary (S) protocols were chronically cannulated for hemodynamic/autonomic recordings and determination of BBB permeability (fluorescent Rhodamine-70kDa+FITC-10kDa dyes given ia ). To analyze hypertension- and T-induced BBB changes, paraventricular hypothalamic nuclei (PVN) was harvested and processed for immunofluorescence and transmission electron microscopy Results: SHR-S vs Wistar-S exhibited augmented SAP and reduced pulse interval (PI) variability, decreased spontaneous baroreflex sensitivity (BrS), increased both PVN BBB leakage (11.4±0.6 vs 3.48 %area) and transcytosis (8.1±1.2 vs 4.8±0.8 vesicles/capillary) but no change in tight junctions’expression (TJ, number/capillary). SHR-T showed a near normal autonomic control, resting bradycardia and a partial AP reduction (-9%) accompanied by normalization of both BBB leakage (3.6±1.5 %area) and transcytosis (3.8±0.7 vesicles/capillary), and increased TJs’ extension (60% occupancy of capillary borders) without changing its expression. Hypertension- and T-induced transcytosis changes were confirmed by caveolin-1 immunofluorescence (SHR-S=139±11, Wistar-S=86±8, SHR-T=81±6 arbitrary units). There were significant correlations between the number of transcytotic vesicles x PVN BBB leakage (Y=1.77x -3.46, r 2 =0.722, P<0.001) and BBB leakage x SAP variability (Y=2.30x +16.6, r 2 =0.246, P<0.001) Conclusions: PVN BBB dysfunction in hypertension is due to increased transcytosis without changes in the paracellular pathway. Training ameliorates SHR’s autonomic control by normalizing transcytosis, with an additional TJs structure improvement

Relationship Between Orthostatic Stress Response And Acute Mountain Sickness Susceptibility At High Altitude: Pilot Study

PURPOSE: To determine whether there is a difference in hemodynamic responses to head-up tilt (HUT) in subjects who do, and do not, experience acute mountain sickness (AMS) during exposure to hypobaric hypoxia. We also aimed to determine if those hemodynamic variables altered during HUT correlated with AMS severity. METHODS: Fifteen participants completed three testing sessions: 1) VO2max test to determine workload at 50% VO2max for hypoxia exposure; 2) HUT test consisted of supine rest for 20 min followed by 70° upright tilt for ≤40 min; and 3) six hours of hypobaric hypoxic exposure simulating 4572 m where participants performed two, 30-min cycling bouts and rested when not exercising. During HUT, continuous blood pressure (BP) monitoring was used to assess systolic and diastolic blood pressure (SBP, DBP); mean arterial pressure (MAP); variability in SBP, DBP, and MAP; and heart rate. AMS scores were reported before and after six hours of hypoxic exposure. Statistical analysis included mixed effects ANOVA to determine changes between supine rest and end of HUT and those who scored a ≥ 3 AMS positive (AMS+) and < 3 AMS negative (AMS-) groups. Correlations by linear regression determined associations between HUT hemodynamic responses and AMS scores. Statistical significance was set to p < 0.05. RESULTS: Systolic, diastolic, and mean arterial blood pressure variability (BPV) increased from supine rest to end of HUT (BPV mean difference ± SD for AMS+ & AMS- groups: SBP = 3.5 ± 3.0, 1.2 ± 1.9: DBP = 1.7 ± 1.5, 0.6 ± 0.9: MAP = 2.8 ± 2.9, 1.1 ± 1.4; p = 0.004, 0.004, & 0.006, respectively). Those with higher AMS scores tended to have a greater magnitude of change in SBP, DBP, and MAP variability during the HUT test (r = 0.65, 0.64, & 0.60, respectively). CONCLUSIONS: Increased BPV indicates BP dysregulation, suggesting that AMS+ individuals may have greater disruptions in BP control that could be observable during a postural change prior to hypoxic exposure. BPV during HUT may be a promising predictive variable for AMS but further research is needed. In the future, researchers should consider using sea-level residents and a range of simulated elevations to determine the predictability of AMS susceptibility by BPV.