Assessment Of Baroreflex Sensitivity Research Articles

Impaired cerebral autoregulation detected in early prevasospasm period is associated with unfavorable outcome after spontaneous subarachnoid hemorrhage: an observational prospective pilot study

BackgroundSubarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes.MethodsThe pilot observational study included 29 SAH patients whose CA status was estimated 2–3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2–3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device.ResultsStatistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039).ConclusionsA relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI.Trial registrationClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 - Retrospectively registered, https://www.clinicaltrials.gov/study/NCT06028906.

Impact of squatting on selected cardiovascular parameters among college students

Squatting is an active posture test used in assessing baroreflex sensitivity, and the array of patients a physiotherapist handles may benefit from this test to avoid the adverse effects of exercise. Therefore, this study is designed to evaluate the effect of squatting on heart rate and blood pressure among undergraduate students. 35 males (mean age = 22.94 ± 1.846) and 40 females (mean age = 22.28 ± 2.075) participated in this experimental study. Demographic data and baseline cardiovascular parameters (blood pressure and heart rate) were taken before exercise. The exercise protocol, the squatting stress test, was done for 2 min, after which post-exercise blood pressure and heart rate were taken at one minute each. A repeated measure ANOVA and independent t-test were used to analyse the difference at the 0.05 alpha level. It was found that there was a significant difference between pre-exercise in lying and squatting post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01), pre-exercise in lying and standing post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01), pre-exercise in standing and standing post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01), and pre-exercise in standing and squatting post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01). Also, there was a significant difference in pre-exercise heart rate between lying and standing (p < 0.05) and not between the first minute and second minute post-squatting or standing exercise systolic blood pressure (p = 0.588) or diastolic blood pressure (p = 0.22–1). In conclusion, squatting trials among undergraduates revealed some statistically significant changes, especially between the cardiopulmonary parameters obtained in a standing position compared to lying and those measured after one minute. Therefore, caution should be observed when administering exercises that require changes in posture.

Innate Sleep Apnea in Spontaneously Hypertensive Rats Is Associated With Microvascular Rarefaction and Neuronal Loss in the preBötzinger Complex.

Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia. To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders: plethysmography and electroencephalographic/electromyographic recordings were used to assess sleep-wake state, breathing parameters, and sleep-disordered breathing; immunocytochemistry was used to assess vascular and neural health; the forced alteration Y maze and Barnes maze were used to assess short- and long-term memories, respectively; and an anesthetized preparation was used to assess baroreflex sensitivity. Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories. Therefore, we postulate that hypertension induces SA through vascular damage in the respiratory column, culminating in neuronal loss in the inspiratory oscillator. This induction of SA, which, in turn, will independently exacerbate hypertension and neural inflammation, increases the rate of vascular dementia.

Treatment with empagliflozin improves cardiac function in infarcted animals associated with increased baroreflex sensitivity

Abstract Background Several clinical and experimental studies have shown an improvement in cardiac function in infarcted patients and animals (diabetic or not) when treated with empagliflozin, as well as an improvement in outcomes in patients with heart failure with reduced ejection fraction or with preserved ejection fraction. Hypothesis: Treatment with empagliflozin for 14 days (10 mg/kg) improves cardiac function in infarcted rats, secondary to increased baroreflex sensitivity. Methods Wistar rats were divided into 2 groups: AMI - acute myocardial infarction (n=8) and AMI+EMPA - acute myocardial infarction + Empagliflozin (n=8). The animals in both groups were anesthetized and submitted to thoracotomy and ligature of the left coronary artery. The animals in the AMI+EMPA group received daily, through oral gavage, 10 mg/kg of empagliflozin, for 14 days. After this period, an echocardiographic examination was performed, followed by cannulation of the femoral vein and artery, to assess hemodynamic parameters and baroreflex activity. The results were evaluated for normality. Data were compared by Student's t tests. And the relationship between the parameters was tested by Pearson's correlation. Results are presented as mean and standard deviation. Results In the echocardiographic evaluation, an improvement in diastolic function indexes was observed in the AMI+EMPA group in relation to the AMI group: E'/A' ratio (1.584 ± 0.437 vs 0.589 ± 0.129), E/E' ratio (14.11 ± 3.946 vs 29.92 ± 6.878) and systolic function: SF (29.30% ± 7.974 vs 19.20% ± 2.445), EF (53.86% ± 11.78 vs 37.91% ± 4.212), FAC (39.31% ± 7.135 vs 23.51 ± 3.940). There was a reduction in mean blood pressure in the AMI+EMPA group (102.4 mmHg ± 6,408) compared to the AMI group (110.7 mmHg ± 8,514) and in diastolic blood pressure (84.4 mmHg ± 3.889 vs 92.8 mmHg ± 7.664). In the assessment of baroreflex sensitivity, an improvement in tachy and bradycardic indexes was observed in the treated animals: tachycardic index (5.021 bpm/mmHg ± 0.346 vs 3.214 bpm/mmHg ± 0.418) and bradycardic index (1.569 bpm/mmHg ± 0.148 vs 0.73 bpm/ mmHg ± 0.046). In addition, the systolic function expressed by the FAC was positively associated with the reflex tachycardic index (p: 0.008; r: 0.616) and to the E'/A' ratio (p: 0.025; r: 0.576) and negatively with PAD (p: 0.040; r: -0.503). Conclusion Treatment with Empagliflozin in infarcted rats was able to improve left ventricular systolic and diastolic function associated with improved performance of arterial baroreceptors.

Abstract P2065: Mice Under Transverse Aortic Constriction And Treated With Sodium Oxalate May Develop Cardiac Dysfunction

Background: Experimental models are important for studying the mechanisms of cardiovascular disease. The transverse aortic constriction model (TAC) is among the most used in the literature for the study of cardiac hypertrophy. The soluble sodium oxalate (OXA) model generates renal injury but is also associated with cardiac hypertrophy through hypertensive-like lesions. There is little information in the literature on direct hemodynamic recording in both models mentioned, as well as there is no data on the changes caused by the association of these two models. Therefore, our objective is to evaluate whether TAC associated with OXA gavage could be a new model of cardiac dysfunction. Methods and Results: Male C57BL mice were randomized as follows: SHAM animals that received gavage with vehicle or OXA solution, and animals submitted to TAC and gavage with vehicle or OXA solution. Echocardiography and metabolic cage assessment were used to quantify cardiac and renal function. Direct blood pressure (BP) recording was also performed to assess baroreflex sensitivity and histological analysis. The TAC+OXA group had the highest BP values (mean BP:SHAM:100±5.0 vs. TAC+OXA:132±4.8mmHg, p&lt;0.01), the highest pulmonary congestion index, an increase in the double product, an important reduction in autonomic modulation (AM), heart rate variability (HRV) (SD-PI: SHAM+OXA:12.5±1.8 vs. TAC+OXA:2.8±0.2ms, p&lt;0.01) and alpha index (SHAM:3.6±1.0 vs. TAC+OXA:0.6±0.1, p=0.04). The TAC group showed the greatest weight of the ventricles and the greatest increase in blood pressure variability (DP-SBP). The SHAM+OXA group showed an increase in AM and HRV. The three groups showed a significant reduction in reflex tachycardia. Conclusion: TAC surgery provided cardiac hypertrophy, reduction in reflex tachycardia and changes in autonomic modulation. In the absence of TAC, the treatment with OXA for 15 days increased autonomic modulation. TAC surgery in conjunction with OXA gavage caused greater cardiac dysfunction.

A comparison of four common mathematical models to assess baroreflex sensitivity.

Different methods have been used to assess baroreflex gain in experiments where changes in the carotid sinus pressure or the arterial blood pressure using different techniques provoke a baroreflex response, usually a rapid variation of heart rate. Four mathematical models are most used in the literature: the linear regression, the piecewise regression, and two different four-parameter logistic equations: equation 1, Y = (A1-D1)/[1 + eB1(X - C1) ] + D1; equation 2, Y = (A2-D2)/[1 + (X/C2)B2 ] + D2. We compared the four models regarding the best fit to previously published data in all vertebrate classes. The linear regression had the worst fit in all cases. The piecewise regression generally exhibited a better fit than the linear regression, though it returned a similar fit when no breakpoints were found. The logistic equations showed the best fit among the tested models and were similar to each other. We demonstrate that equation 2 is asymmetric and the level of asymmetry is accentuated according to B2. This means that the baroreflex gain calculated when X = C2 is different from the actual maximum gain. Alternatively, the symmetric equation 1 returns the maximum gain when X = C1. Furthermore, the calculation of baroreflex gain using equation 2 disregards that baroreceptors may reset when individuals experience different mean arterial pressures. Finally, the asymmetry from equation 2 is a mathematical artifact inherently skewed to the left of C2, thus bearing no biological meaning. Therefore, we suggest that equation 1 should be used instead of equation 2.

Baroreflex sensitivity is associated with markers of hippocampal gliosis and dysmyelination in patients with psychosis.

Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants with a nonpsychotic affective disorder and participants with no history of psychiatric disease; (2) to examine the relationship between hippocampal neurometabolites and baroreflex sensitivities in these three groups. We hypothesized that baroreflex sensitivity would be reduced and correlated with hippocampal neurometabolite levels in participants with psychosis, but not in the control groups. We assessed baroreflex sensitivity during the Valsalva maneuver separated into vagal and adrenergic components. Metabolite concentrations for cellular processes were quantitated in the entire multivoxel hippocampus using H1-MR spectroscopic (MRS) imaging and were compared with baroreflex sensitivities in the three groups. Vagal baroreflex sensitivity (BRS-V) was reduced in a significantly larger proportion of participants with psychosis compared with patients with nonpsychotic affective disorders, whereas participants with psychosis had increased adrenergic baroreflex sensitivity (BRS-A) compared with participants with no history of psychiatric disease. Only in psychotic cases were baroreflex sensitivities associated with hippocampal metabolite concentrations. Specifically, BRS-V was inversely correlated with myo-inositol, a marker of gliosis, and BRS-A was positively correlated with energy dependent dysmyelination (choline, creatine) and excitatory activity (GLX). Abnormal baroreflex sensitivity is common in participants with psychosis and is associated with MRS markers of hippocampal pathology. Future longitudinal studies are needed to examine causality.

Assessment of baroreflex sensitivity during isometric handgrip exercise and oscillatory lower body negative pressure

ObjectivesBaroreflex sensitivity (BRS) is an estimate of autonomic control of cardiovascular system via the baroreflex arc. It has been suggested that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain, which facilitates the simultaneous rise in blood pressure (BP) and heart rate during the exercise. This study investigated the effects of isometric handgrip exercise (IHE) on baroreflex gain and frequency dependence of baroreflex sensitivity while fluctuations in arterial BP were generated. MethodsThirteen healthy men performed IHE at 20% and 30% of their maximum voluntary contraction (MVC), while oscillatory lower body negative pressure (OLBNP) of 40 mmHg was applied in 0.1 and 0.25 Hz frequencies. ResultsCompared to the OLBNP at 0.25 Hz frequency alone, the baroreflex gain for diastolic BP (DBP) was significantly reduced with the addition of IHE at 20% and 30% of MVC in the high frequency band. At rest (without IHE and OLBNP) the baroreflex gain was significantly more in the high frequency band for DBP, but the baroreflex gain for DBP was not significantly different when IHE + OLBNP were applied at 20% and 30% of MVC in both frequencies. ConclusionsThe significant reduction of DBP baroreflex gain with the addition of graded IHE might indicate that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain at a high frequency band (0.25 Hz). The frequency-dependent phenomenon of BRS was altered when IHE and OLBNP were applied, meaning that the frequency dependence of BRS was nullified during IHE.

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

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

Effects of long-acting bronchodilators on cardiac autonomic control in COPD

IntroductionSeveral studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting β2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved. MethodsWe performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial - NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a predictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test). Results34 patients attended four visits to receive either tiotropium 18µg, glycopyrronium 44µg, indacaterol 150 µg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate compared to placebo. No significant differences were observed for HRV and BRS between active drugs and placebo in supine position or after passive rising. ConclusionWe did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.

Changes in autonomic nervous system during cerebral desaturation episodes in aneurysmal subarachnoid hemorrhage.

Little evidence is available on the effect of regional cerebral desaturation (rCD) episodes that occur in the first days after aneurysm subarachnoid haemorrhage (aSAH) on the autonomic nervous system activity and on cardiovascular hemodynamics. In this study, we aimed to determine the impact of rCD episodes, developed within 5days of aSAH, on the autonomic nervous system based on the assessment of baroreflex sensitivity (BRS) and on cardiac output (CO) and cardiac index (CI), and on cerebral autoregulation (CA). Of 96 patients with aSAH, 36 patients (aged 57 (48-69)) met the inclusion criteria and were included in the study. Regional cerebral oxygen saturation and rCD episodes were evaluated using near-infrared spectroscopy. CA was quantified by the correlation coefficient (TOxa). Cardiac output (CO) and cardiac index (CI) were monitored using the FloTrack®/EV1000. Baroreflex sensitivity (BRS) was assessed using the cross-correlation method. Scores of 1 to 3 in Glasgow Outcome Scale were classified as a poor outcome. During episodes of rCD, BRS decreased significantly compared to baseline (p=0.027) in patients who had a total duration of rCD episodes of more than 10hours. During rCD episodes, CA improved slightly in comparison to baseline (p=0.027). The threshold associated with poor outcome was: rSO2<62% (p=0.002). BRS decreased in patients who had a total duration rCD episodes of more than 10 hours within the 5 days of aSAH. These results might partly explain the relationship between lower BRS and worse prognosis.

Stress and the baroreflex.

The stress response to emotions elicits the release of glucocorticoids from the adrenal cortex, epinephrine from the adrenal medulla, and norepinephrine from the sympathetic nerves. The baroreflex adapts to buffer these responses to ensure that perfusion to the organs meets the demands while maintaining blood pressure within a within a narrow range. While stressor-evoked autonomic cardiovascular responses may be adaptive for the short-term, the recurrent exaggerated cardiovascular stress reactions can be maladaptive in the long-term. Prolonged stress or loss of the baroreflex's buffering capacity can predispose episodes of heightened sympathetic activity during stress leading to hypertension, tachycardia, and ventricular wall motion abnormalities. This review discusses 1) how the baroreflex responds to acute and chronic stressors, 2) how lesions in the neuronal pathways of the baroreflex alter the ability to respond or counteract the stress response, and 3) the techniques to assess baroreflex sensitivity and stress responses. Evidence suggests that loss of baroreflex sensitivity may predispose heightened autonomic responses to stress and at least in part explain the association between stress, mortality and cardiovascular diseases.

Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson's Disease.

BackgroundAutonomic disorders are an important non-motor feature of Parkinson’s disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD.Materials and MethodsEighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method.Results and ConclusionThere was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.

HP06: Baroreflex sensitivity is predictor of mortality in general elderly population

Baroreflex sensitivity (BRS) is known to be a predictor of morbidity and mortality in metabolic and cardiovascular diseases. However, although we know that BRS decreases with age, we do not know whether BRS is predictive of mortality in general elderly population. The objective of this work is to study the predictive value of BRS in the mortality of an elderly population. We followed-up 1011 healthy elderly subjects (PROOF study, 68.4 ± 0.8 years, 609 women) during 19 years. At inclusion, we continuously recorded electrocardiogram, blood pressure, and respiration during 15 minutes insupine and upright position. BRS has been estimated using the sequence method. The mortality risk hazard ratio (HR) was calculated by comparing the first and the third terciles for BRS index, ajusted for sexe and cardiovascular risk factors. 207 subects passed away during the follow-up (20.5%) ; 74 from cardiovascular cause (7.3%). As results always show a sexe effect, men and women were analyzed separately. For women, HR were not statisticaly significant. For men, there was an increase of the risk when comparing BRS < 3.08 and BRS > 4.63 mmHg measured in upright position (HR 3.16 [1.32 – 3.54 ; p < 0.002]. Results were unsignificant for BRS measured in supine position. This study highlights that clinical value of BRS assessment could be usefull in general elderly population, more in men than in women. Moreover, BRS seems to be more informative when estimated in the upright position which is rarely the case for its recording in routine use.

Reduced baroreflex sensitivity and increased splenic activity in patients with severe obstructive sleep apnea

Background and aimsSevere obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Experimental evidence suggests that this risk may be mediated by chronic sympathetic hyperactivation and systemic inflammation, but the precise mechanisms remain to be unraveled. Our aim was to evaluate whether severe OSA patients are characterized by increased sympathetic and hematopoietic activity, potentially driving atherosclerosis. MethodsUntreated patients with severe OSA (apnea-hypopnea index (AHI) > 30 per hour) were matched with mild OSA patients (AHI<15 & >5 per hour) according to age, sex, and body mass index. Study objectives were to assess baroreflex sensitivity (BRS) and heart-rate variability (HRV) using continuous finger blood pressure measurements, hematopoietic activity in the bone marrow and spleen, and arterial inflammation with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). ResultsA total of 34 subjects, 17 per group, were included in the analysis. Mean age was 60.7 ± 6.2 years, 24 (70.6%) were male. Mean AHI was 40.5 ± 12.6 per hour in the severe OSA group, and 10.5 ± 3.4 per hour in the mild OSA group. Participants with severe OSA were characterized by reduced BRS (5.7 [4.6–7.8] ms/mmHg in severe vs 8.2 [6.9–11.8] ms/mmHg in mild OSA, p = 0.033) and increased splenic activity (severe OSA 18F-FDG uptake 3.56 ± 0.77 vs mild OSA 3.01 ± 0.68; p = 0.036). HRV, bone marrow activity and arterial inflammation were comparable between groups. ConclusionsPatients with severe OSA are characterized by decreased BRS and increased splenic activity. Randomized controlled trials are warranted to assess whether OSA treatment reduces sympathetic and splenic activity.

Autonomic biomarkers of shock in idiopathic systemic capillary leak syndrome.

ObjectiveThe term Idiopathic Systemic Capillary Leak Syndrome (ISCLS) refers to an uncommon condition of severe distributive shock, resulting from an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesise that the autonomic nervous system (ANS) fails in regulating the response to hypovolemia in acute ISCLS and that ANS variables characterise the progression to the recovery.DesignProspective cohort study of patients admitted to ICU for severe ISCLS flares.SettingSingle, referral center in Italy for ISCLS.PatientsAnalysis of cardiovascular signals recorded during seven severe ISCLS attacks and one prodromal period in five patients.InterventionsANS was studied non-invasively by means of heart rate variability (HRV) and blood pressure variability analysis, as an estimation of vagal and sympathetic modulation directed to the heart and vessels. Heart rate and systolic arterial pressure (SAP) variability were also used to assess baroreflex sensitivity. ANS variables were measured during the subsequent phases which characterise ISCLS flares, namely the acute phase, the post-acute phase, and the recovery phase.Measurements and main resultsHRV was severely depressed during the acute phase accounting for the loss of ANS modulation during massive capillary extravasation. This phase was characterised by shock and impaired baroreflex control, which allowed SAP to oscillate driven by respiratory activity. Impending shock and transition from shock to a post-acute phase were marked by change of baroreflex spectral variables. The baroreflex control was fully restored during recovery.ConclusionsANS modulation and baroreflex control are severely impaired during the acute haemodynamic instability which characterises ISCLS crises and their progressive restoration may be a clue of improvement. ANS indices during ISCLS flares might serve as useful biomarkers, able to timely announce the transition from one phase to the subsequent one, thus helping to adapt therapy accordingly.

Comparison of frequency domain measures based on spectral decomposition for spontaneous baroreflex sensitivity assessment after Acute Myocardial Infarction

The objective of this study is to present a new method to assess in the frequency domain the directed interactions between the spontaneous variability of systolic arterial pressure (SAP) and heart period (HP) from their linear model representation, and to apply it for studying the baroreflex control of arterial pressure in healthy physiological states and after acute myocardial infarction (AMI). The method is based on pole decomposition of the model transfer function and on the following evaluation of causal measures of coupling and gain from the poles associated to low frequency (0.04−0.15 Hz) oscillatory components. It is compared with traditional non-causal approaches for the spectral analysis of the baroreflex gain, and with causal approaches based on the directed coherence, in a group of AMI patients and in Young and Old healthy controls studied at rest and during head-up tilt. Analysis of feedforward interactions from RR to SAP is also performed. Our results support the importance of using local causal approaches to quantify separately baroreflex and feedforward interactions between RR and SAP, allowing both to confirm known physiological behaviors (e.g., weaker baroreflex effectiveness and lower sensitivity after AMI) and to suggest novel findings (e.g., preserved low frequency baroreflex response to postural stress after AMI). We also find that the postural stress alters feedforward interactions selectively across groups, being related to decreased coupling only in Young and to increased gain mostly in AMI. These results have a significance for the clinical assessment of the baroreflex and the physiological evaluation of cardiovascular interactions.

Baroreflex Sensitivity Assessment: How Many Sit‐Stand Maneuvers to Evaluate Cardiovascular Disease Risk?

OBJECTIVE Although recent evidence suggests that 15 cycles of repeated sit-stand maneuvers may be a useful method for baroreflex sensitivity (BRS) assessment, it remains unclear how many times the maneuver should be performed to estimate BRS for cardiovascular disease (CVD) risk assessment with minimal effort. The purpose of this study was to explore the minimal cycles of sit-stand maneuvers for BRS assessment. We hypothesized that less than 15 cycles of repeated sit-stand maneuvers can evaluate the BRS for CVD risk assessment. METHODS 183individuals (62 ± 12 years, 72% Women) were analyzed cross-sectionally in this study. In the assessment of BRS, the beat-to-beat changes of R-R interval and SBP were measured during 1) 5 minutes of resting seat condition and 2) 5 minutes of the repeated sit-stand maneuvers at 0.05 Hz (i.e. 15 cycles of 10-second sit and 10-second stand). BRS gain, power spectral density (PSD) of R-R interval and SBP were calculated from the 6 conditions: seated rest, 3, 6, 9, 12, 15 cycles of the repeated sit-stand maneuvers using spectral and transfer function analyses. In addition to traditional CVD risk measurements, including hemodynamics and blood biomarker measures, carotid distensibility was calculated from carotid pulse pressure and intra-beat changes of carotid diameter. The associations of age and carotid distensibility with BRS gains calculated from the 6 conditions were tested through partial correlation analysis adjusted for sex. The partial correlation coefficients were compared by Fisher r-to-z transformation analysis. RESULTS The PSDs of R-R interval and SBP were progressively increased as the cycles of repeated sit-stand maneuvers increased. The BRS gains calculated from all the 6 conditions were negatively associated with age and carotid distensibility (all tests were P < 0.001). The BRS gain calculated from the 6 cycles and over of repeated sit-stand maneuvers were strongly associated with age and carotid distensibility compared to the equivalents calculated from the seated rest and 3 cycles of repeated sit-stand maneuvers (P < 0.05). The strength of the correlation did not increase with the greater number of 6 cycles of sit-stand maneuvers. Furthermore, forward stepwise regression analysis showed that age, sex, carotid distensibility, brachial systolic pressure, heart rate, and HDL-cholesterol were selected as the covariates of BRS gains calculated from 6 cycles of the sit-stand maneuvers, and these covariates explained over 60% variance of the BRS gain. CONCLUSION Our results suggest that BRS gain calculated from at least 6 cycles of repeated sit-stand maneuvers is strongly associated with CVD risk factors. We also observed that variabilities of R-R interval and SBP progressively increased as the number of sit-stand cycles increased.

High-intensity, whole-body exercise improves blood pressure control in individuals with spinal cord injury: A prospective randomized controlled trial.

Blood pressure regulation following spinal cord injury (SCI) is often compromised due to impaired vascular sympathetic control, leading to increased reliance on cardiovagal baroreflex sensitivity to maintain pressure. Whole-body exercise improves cardiovagal baroreflex sensitivity in uninjured individuals, though has not been explored in those with SCI. Our objective was to determine changes in cardiovagal baroreflex sensitivity following 6 months of high-intensity, whole-body exercise in individuals with SCI compared to lower-intensity, arms only exercise, or waitlist. This randomized controlled trial recruited individuals with SCI aged 18–40 years old. Sixty-one individuals were randomized, with 38 completing at least one cardiovagal baroreflex sensitivity assessment. Whole-body exercise was performed with hybrid functional electrical stimulation rowing prescribed as two to three times per week, for 30–60 minutes with a target heart rate of >75% of maximum. The arms only exercise group performed upper body rowing exercise with the same prescription as whole-body exercise. Waitlist controls were not enrolled in any explicit training regimen. After 6 months, those in arms only exercise or waitlist crossed over to whole-body exercise. Cardiovagal baroreflex sensitivity was assessed via the neck suction technique at baseline and at three-month intervals thereafter. Intention to treat analysis with a structured equation model demonstrated no significant effect of waitlist control or arms only exercise on cardiovagal baroreflex sensitivity. Whole-body exercise significantly improved cardiovagal baroreflex sensitivity at 6 months for those initially randomized (p = 0.03), as well as those who crossed over from arms only exercise or waitlist control (p = 0.03 for each). However, amount of exercise performed and aerobic gains (VO2max) each poorly correlated with increases in cardiovagal baroreflex sensitivity (R2<0.15). In post-hoc analyses, individuals with paraplegia made significantly greater gains in baroreflex sensitivity compared to those with tetraplegia (p = 0.02), though gains within this group were again poorly correlated to gains in aerobic capacity. Clinicaltrials.gov number NCT02139436.

Functional plasticity of cardiac efferent neurons contributes to traumatic brain injury-induced cardiac autonomic dysfunction

Traumatic brain injury (TBI) frequently causes cardiac autonomic dysfunction (CAD), irrespective of its severity, which is associated with an increased morbidity and mortality in patients. Despite the significance of probing the cellular mechanism underlying TBI-induced CAD, animal studies on this mechanism are lacking. In the current study, we tested whether TBI-induced CAD is associated with functional plasticity in cardiac efferent neurons. In this regard, TBI was induced by a controlled cortical impact in rats. Assessment of heart rate variability and baroreflex sensitivity indicated that CAD was developed in the sub-acute period after moderate and severe TBI. The cell excitability was increased in the stellate ganglion (SG) neurons and decreased in the intracardiac ganglion (ICG) neurons in TBI rats, compared with the sham-operated rats. The transient A-type K+ (KA) currents, but not the delayed rectifying K+ currents were significantly decreased in SG neurons in TBI rats, compared with sham-operated rats. Consistent with these electrophysiological data, the transcripts encoding the Kv4 α subunits were significantly downregulated in SG neurons in TBI rats, compared with sham-operated rats. TBI causes downregulation and upregulation of M-type K+ (KM) currents and the KCNQ2 mRNA transcripts, which may contribute to the hyperexcitability of the SG neurons and the hypoexcitability of the ICG neurons, respectively. In conclusion, the key cellular mechanism underlying the TBI-induced CAD may be the functional plasticity of the cardiac efferent neurons, which is caused by the regulation of the KA and/or KM currents.