Decrease In Baroreflex Sensitivity Research Articles

Biphasic changes in spontaneous cardiovagal baroreflex sensitivity during passive hyperthermia

Successful adaptation to passive hyperthermia requires continual adjustment of circulation, which is mediated mainly by the autonomic nervous system. The goal of this study was to explore the alterations in spontaneous cardiovagal baroreflex sensitivity (BRS) during exposure to a hot environment. To continuously follow changes in core body temperature (Tc), haemodynamics, and BRS, male Wistar-Kyoto rats were implanted with telemetric transmitters. BRS at an ambient temperature of 23 °C was not steady but oscillated with a maximum power in the range of 0.02–0.2 Hz. Exposure to hot air immediately shifted the distribution of BRS to higher values, although Tc remained unchanged (37.2 (0.3) °C), and the average BRS changed from 1.3 (0.3) to 3 (1.4) ms.mmHg−1, p < 0.0001. The degree of initial cardiovagal baroreflex sensitization explained 57% of the variability in the time to the onset of arterial pressure decline (p = 0.0114). With an increasing Tc (>38.8 (0.6) °C), BRS non-linearly declined, but haemodynamic parameters remained stable even above a Tc of 42 °C when the cardiovagal baroreflex was virtually non-operative. Abrupt full desensitization of the cardiovagal baroreflex with a muscarinic blocker did not induce arterial pressure decline. Our data indicate that a progressive decrease in BRS during passive hyperthermia does not induce haemodynamic instability. The positive association between initial cardiovagal baroreflex sensitization and the time to the onset of arterial pressure decline may reflect the potential protective role of parasympathetic activation during exposure to a hot environment.

Effects of exercise intensity on vascular and autonomic components of the baroreflex following glucose ingestion in adolescents

PurposeTo investigate the effects of an oral glucose tolerance test (OGTT) on baroreflex sensitivity (BRS) in a sample of healthy adolescents, and how acute exercise bouts of different intensities alter the effects of the OGTT on BRS.MethodsThirteen male adolescents (14.0 ± 0.5 years) completed three conditions on separate days in a counterbalanced order: (1) high-intensity interval exercise (HIIE); (2) moderate-intensity interval exercise (MIIE); and (3) resting control (CON). At ~ 90 min following the conditions, participants performed an OGTT. Supine heart rate and blood pressure were monitored continuously at baseline, 60 min following the conditions, and 60 min following the OGTT. A cross-spectral method (LFgain) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain divided by AC (LFgain/AC) was used as the autonomic component.ResultsAlthough non-significant, LFgain moderately decreased post-OGTT when no exercise was performed (pre-OGTT = 24.4 ± 8.2 ms mmHg− 1; post-OGTT = 19.9 ± 5.6 ms mmHg− 1; ES = 0.64, P > 0.05). This was attributed to the decrease in LFgain/AC (pre-OGTT = 1.19 ± 0.5 ms µm− 1; post-OGTT = 0.92 ± 0.24 ms µm− 1; ES = 0.69, P > 0.05). Compared to CON (Δ = − 4.4 ± 8.7 ms mmHg− 1), there were no differences for the pre–post-OGTT delta changes in LF/gain for HIIE (Δ = − 3.5 ± 8.2 ms mmHg− 1) and MIIE (Δ = 1.3 ± 9.9 ms mmHg− 1) had no effects on BRS following the OGTT (all ES < 0.5). Similarly, compared to CON (Δ = − 0.23 ± 0.40 ms µm− 1) there were no differences for the pre–post-OGTT delta changes in LF/gain for HIIE (Δ = − 0.22 ± 0.49 ms µm− 1) and MIIE (Δ = 0.13 ± 0.36 ms µm− 1).ConclusionA moderate non-significant decrease in BRS was observed in adolescents following a glucose challenge with no apparent effects of exercise.

Microglia and brain angiotensin type 1 receptors are involved in desensitising baroreflex by intracerebroventricular hypertonic saline in male Sprague-Dawley rats.

High salt diet alters cardiovascular control by increasing concentration of sodium ions (Na+) in cerebrospinal fluid (CSF) and is a risk factor for hypertension. Hypernatremic conditions activate microglia and upregulate renin-angiotensin system in the brain. Thus, we checked if chronic elevation of CSF Na+ affects neural control of circulatory system via microglia and brain angiotensin type 1 receptors (AT1Rs). Normotensive adult male Sprague-Dawley rats received two-week intracerebroventricular (ICV) infusion of either isoosmotic saline (0.9% NaCl); hyperosmotic saline (5% NaCl); 5% NaCl with minocycline - inhibitor of microglia; 5% NaCl with losartan - AT1R blocker. Fluid intake, urine output, and urinary Na+ excretion were measured before and during ICV infusions. At the end of ICV infusions, blood pressure and heart rate were recorded in awake rats at rest, in response to acute air jet stressor, during pharmacological evaluation of baroreflex, and after autonomic ganglia blockade. CSF and blood were collected for evaluation of Na+ concentration. Baroreflex was blunted in rats ICV infused with 5% NaCl. ICV treatment with losartan or minocycline prevented decrease in baroreflex sensitivity. Hemodynamic parameters at rest, in response to acute stressor and autonomic ganglia blockade were similar in all groups. Neither treatment affected water intake, urine output and urinary Na+ excretion. ICV infusion of 5% NaCl resulted in higher concentration of Na+ in CSF than in control group (0.9% NaCl) and in plasma. Our results indicate that chronic ICV infusion of hyperosmotic saline blunts baroreflex in normotensive rats and this desensitization is mediated by microglia and AT1Rs.

Cardiovascular Autonomic Profile in Women With Premenstrual Syndrome

Introduction: The premenstrual syndrome (PMS) is a constellation of somatic and psychogenic symptoms that appear during late luteal (LL) phase of the menstrual cycle. Since many symptoms could be related to the autonomic nervous system, we hypothesized that the sympathetic nervous system is perturbed in PMS.Methods: The cardiovascular autonomic profile of nine women with PMS (30.4 ± 2.5 years) were compared to that of nine healthy controls (30 ± 2.5 years) during their early follicular (EF) and LL phases of the menstrual cycle. Plasma norepinephrine (NE) concentrations, power spectral analysis of heart rate and systolic blood pressure (BP), and baroreflex sensitivity (BRS) were assessed during recumbency and a head-up tilt (HUT). Cardiovascular responsiveness to α1- and β-adrenoreceptor agonists (phenylephrine and isoproterenol, respectively) were also assessed.Results: In the LL phase, the plasma NE concentrations in women with PMS during recumbency and a HUT were lower than those in women without PMS [180 ± 30 vs. 320 ± 50 pg/ml; p = 0.04 (recumbent), and 480 ± 70 vs. 940 ± 180 pg/ml: p = 0.02 (HUT)]. In the LL phase, the dose of phenylephrine required to increase systolic BP by 15 mmHg in women with PMS was significantly greater than that in women without PMS (202 ± 30 μg vs. 138 ± 20 μg; p = 0.02). Sympathetic and vagal cardiac control indices were comparable in the two groups in the menstrual phases. In women with PMS, the value of LFSBP in the LL phase was lower than that in the EF phase (0.98 ± 0.2 vs. 1.77 ± 0.4 mmHg2, p = 0.04). The increase in LFSBP in women with PMS in the LL phase during HUT was greater than that in the controls, 5.2 ± 0.9 vs. 3.1 ± 0.5 mmHg2, p = 0.045, and this increase was associated with a significant decrease in BRS.Conclusion: In women with PMS without psychogenic symptoms, the sympathetic control of their circulation is not dominant during the LL phase of their menstrual cycle.

A1222 Exercise training enhances baroreflex and depressor via activation of central ACE2-Ang(1–7)-Mas axis in SHR

Objectives: To investigate the effects of exercise training on the development and progression of hypertension, blood pressure regulation and the gene and protein expression of angiotensin converting enzyme 2 (ACE2) and MAS receptors in the paraventricular nucleus (PVN). Methods: Male 6 weeks of old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were randomly assigned to the sedentary (Sed) or the exercise training (ExT) group. Exercise training was performed on a treadmill for 20 weeks (18–20 m/min, 60 min/d, 5d/wk). Blood pressure, baroreflex sensitivity (BRS) and the mRNA and protein expression of ACE2 and Mas receptors in the PVN were determined. Alterations of BRS were evaluated before and after intracerebroventricular (ICV) injection of angiotensin1–7 (Ang1–7) and its antagonist A779, respectively. Results: BP was over 140mmHg in the 8th wk of SHR + Sed, but exercise training postponed 2 weeks of the development of hypertension and retarded hypertension progression in SHR. Also, exercise training prevented the decrease in BRS in the SHR + ExT compared with SHR + Sed (P < 0.01). ICV injection of A779 inhibited the BRS in SHR + ExT, which abolished the benefits of exercise training (P < 0.01), but had no influence in SHR + Sed. In contrast, angiotensin1–7 enhanced BRS in sedentary and trained SHR (P < 0.05). Exercise training up-regulated the mRNA and protein expression of ACE2 and Mas receptors in the PVN in SHR, buy not in WKY (P < 0.01). Conclusion: Early exercise training postpones the progression of prehypertension and improves blood pressure regulation, which is associated with the enhanced function of central ACE2-Ang (1–7)-Mas axis. (Support by the National Natural Science Foundation of China (No.81372111) and the Natural Science Foundation of Fujian Province (No.2014 J01339)

Post-ictal Modulation of Baroreflex Sensitivity in Patients With Intractable Epilepsy.

Objective: Seizure-related autonomic dysregulation occurs in epilepsy patients and may contribute to Sudden Unexpected Death in Epilepsy (SUDEP). We tested how different types of seizures affect baroreflex sensitivity (BRS) and heart rate variability (HRV). We hypothesized that BRS and HRV would be reduced after bilateral convulsive seizures (BCS).Methods: We recorded blood pressure (BP), electrocardiogram (ECG) and oxygen saturation continuously in patients (n = 18) with intractable epilepsy undergoing video-EEG monitoring. A total of 23 seizures, either focal seizures (FS, n = 14) or BCS (n = 9), were analyzed from these patients. We used 5 different HRV measurements in both the time and frequency domains to study HRV in pre- and post-ictal states. We used the average frequency domain gain, computed as the average of the magnitude ratio between the systolic BP (BPsys) and the RR-interval time series, in the low-frequency (LF) band as frequency domain index of BRS in addition to the instantaneous slope between systolic BP and RR-interval satisfying spontaneous BRS criteria as a time domain index of BRS.Results: Overall, the post-ictal modulation of HRV varied across the subjects but not specifically by the type of seizures. Comparing pre- to post-ictal epochs, the LF power of BRS decreased in 8 of 9 seizures for patients with BCS; whereas following 12 of 14 FS, BRS increased. Similarly, spontaneous BRS decreased following 7 of 9 BCS. The presence or absence of oxygen desaturation was not consistent with the changes in BRS following seizures, and the HRV does not appear to be correlated with the BRS changes. These data suggest that a transient decrease in BRS and temporary loss of cardiovascular homeostatic control can follow BCS but is unlikely following FS.Significance: These findings indicate significant post-ictal autonomic dysregulation in patients with epilepsy following BCS. Further, reduced BRS following BCS, if confirmed in future studies on SUDEP cases, may indicate one quantifiable risk marker of SUDEP.

Computational model-based assessment of baroreflex function from response to Valsalva maneuver.

Functional metrics of autonomic control of heart rate, including baroreflex sensitivity, have been shown to be strongly associated with cardiovascular risk. A decrease in baroreflex sensitivity with aging is hypothesized to represent a contributing causal factor in the etiology of primary hypertension. To assess baroreflex function in human subjects, two complementary methods to simulate the response in heart rate elicited by the Valsalva maneuver were developed and applied to data obtained from a cohort of healthy normal volunteers. The first method is based on representing the baroreflex arc as a simple linear filter, transforming changes in arterial pressure to changes in R-R interval. The second method invokes a physiologically based model for arterial mechanics, afferent baroreceptor strain-dependent firing, and control of heart rate via central autonomic response to changes in afferent inputs from aortic and carotid sensors. Analysis based on the linear filter model reveals that the effective response time of the baroreflex arc tends to increase with age in healthy subjects and that the response time/response rate is a predictor of resting systolic pressure. Similar trends were obtained based on the physiologically based model. Analysis of the Valsalva response using the physiologically based model further reveals that different afferent inputs from the carotid sinus and the aortic arch baroreceptors govern different parts of the heart rate response. The observed relationship between baroreflex sensitivity and systolic pressure is surprising because hypertensive subjects were excluded from the study, and there was no observed relationship between arterial pressure and age. NEW & NOTEWORTHY We introduce two methods to assess baroreflex function from data recorded from human subjects performing the Valsalva maneuver. Results demonstrate that the baroreflex response time tends to increase with age in healthy subjects, that response time represents a predictor of resting systolic pressure, and that the Valsalva response reveals different effects mediated by baroreceptors in the carotid sinus compared with those in the aortic arch.

Comparison of Different Strategies to Assess Cardiac Baroreflex Sensitivity Based on Transfer Function Technique in Patients Undergoing General Anesthesia.

Baroreflex sensitivity (BRS) can be noninvasively assessed from heart period (HP) and arterial pressure (AP) variability series via the estimation of the gain of the transfer function (TF) in the low frequency (LF, 0.04-0.15 Hz) band. However, different strategies can be adopted to pick the value of the TF gain and different fiducial AP values can be considered. In this study we compared different strategies to reduce the TF gain into a unique maker: i) sampling the TF gain in correspondence of the maximum of the HP-AP squared coherence; ii) sampling the TF gain at the weighted average of the central frequencies of AP spectral components; iii) calculating the average of the TF gain in the LF band. Indexes were computed using alternatively systolic AP (SAP) or diastolic AP (DAP) series in combination with HP. Results were obtained in 129 patients undergoing coronary artery bypass graft surgery before (PRE) and after (POST) the induction of general anesthesia with propofol and remifentanil. The reduction of BRS during general anesthesia is expected as a result of overall depression of the cardiovascular control even in this group of pathological subjects already featuring a low BRS before general anesthesia induction. We found that the expected decrease of BRS was observed regardless of the strategy using DAP. Moreover, regardless of series (i.e., SAP or DAP), the sampling of TF gain at the weighted average of the central frequencies of the AP spectral components has the greatest statistical power in distinguishing the two experimental conditions. We recommend the use of this strategy in assessing BRS via TF analysis and a more frequent exploitation of the DAP series.

AltitudeOmics: Baroreflex Sensitivity During Acclimatization to 5,260 m.

Introduction: Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Little is known concerning the adaptive responses of BRS during acclimatization to high altitude at rest and during exercise.Methods: Twenty-one healthy sea-level residents were tested near sea level (SL, 130 m), the 1st (ALT1) and 16th day (ALT16) at 5,260 m using radial artery catheterization. BRS was calculated using the sequence method (direct interpretation of causal link between BP and heartrate). At rest, subjects breathed a hyperoxic mixture (250 mmHg O2, end tidal) to isolate the preponderance of CO2 chemoreceptors. End-tidal CO2 varied from 20 to 50 mmHg to assess peripheral chemoreflex. Rebreathing provoked incremental increase in CO2, increasing BP to assess baroreflex. During incremental cycling exercise to exhaustion, subjects breathed room air.Results: Resting BRS decreased in ALT1 which was exacerbated in ALT16. This decrease in ALT1 was reversible upon additional inspired CO2, but not in ALT16. BRS decrease during exercise was greater and occurred at lower workloads in ALT1 compared to SL. At ALT16, this decrease returned toward SL values.Discussion/Conclusion: This study is the first to report attenuated BRS in acute hypoxia, exacerbated in chronic hypoxia. In ALT1, hypocapnia triggered BRS reduction whilst in ALT16 resetting of chemoreceptor triggered BRS reduction. The exercise BRS resetting was impaired in ALT1 but normalized in ALT16. These BRS decreases indicate decreased control of BP and may explain deteriorations of cardiovascular status during exposure to high altitude.

Glycemic variability in continuous glucose monitoring is inversely associated with baroreflex sensitivity in type 2 diabetes: a preliminary report

BackgroundIt is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM).MethodsThis was a multicenter, prospective, open-label clinical trial. A total of 102 patients with type 2 diabetes were consecutively recruited for this study. GV was assessed by measuring the standard deviation (SD), glucose coefficient of variation (CV), and the mean amplitude of glycemic excursions (MAGE) during CGM. The BRS was analyzed from electrocardiogram and blood pressure recordings using the sequence method on the first day of hospitalization.ResultsA total of 94 patients (mean diabetes duration 9.7 ± 9.6 years, mean HbA1c 61.0 ± 16.8 mmol/mol [7.7 ± 1.5%]) were analyzed. In the univariate analysis, CGM-SD (r = − 0.375, p = 0.000), CGM-CV (r = − 0.386, p = 0.000), and MAGE (r = − 0.395, p = 0.000) were inversely related to BRS. In addition to GV, the level of BRS correlated with the coefficient of variation in the R–R intervals (CVR-R) (r = 0.520, p = 0.000), heart rate (HR) (r = − 0.310, p = 0.002), cardio-ankle vascular index (CAVI) (r = − 0.326, p = 0.001), age (r = − 0.519, p = 0.000), and estimated glomerular filtration rate (eGFR) (r = 0.276, p = 0.007). Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS. These findings remained after adjusting the BRS for age, sex, hypertension, dyslipidemia, HR, eGFR, CAVI, and CGM-mean glucose. Additionally, BRS was divided according to quartiles of the duration of diabetes (Q1–4). BRS decreased after a 2-year duration of diabetes independently of age and sex.ConclusionsGV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients. Measurement of BRS may have the potential to predict CV events in consideration of GV.Trial registration UMIN Clinical Trials Registry UMIN000025964, 28/02/2017

Comprehensive non-invasive cardiac and autonomic assessment in acute ischemic stroke patients: a pilot study.

The aim of this study was to comprehensively determine hemodynamic and autonomic responses during-head up tilt test (HUT) in the acute and recovery phase of ischemic stroke. Cardiovascular parameters, baroreflex sensitivity (BRS), spectral-indices of heart rate (HRV), systolic (sBPV) and diastolic blood pressure variability (dBPV) were measured at rest in ischemic stroke patients (N.=17) and control group (N.=34). Dynamic cardiac autonomic function was assessed using HUT (Delta [rest-tilt]. Controls were examined once whereas stroke group at two timepoints: on admission and in day 10 (recovery period). After a recovery period the stroke group showed significantly higher resting values of systolic blood pressure (sBP, P=0.028), systolic time ratio (STR, P=0.023), high frequency sBPV (HF-sBP, P=0.027), high frequency R-R interval (HF-RRI, P=0.048), power spectral density of sBPV (PSD-sBP, P=0.004) and lower sympathovagal ratio (LF/HF, P=0.005), low frequency R-R interval (LF-RRI, P=0.045), BRS and significantly lower increase in post tilt changes in systolic blood pressure (Delta sBP), total peripheral resistance (Delta TPR) compared to controls. No significant differences were observed for post-tilt in all hemodynamic changes compared to admission. After the recovery period the patient group showed an improved blood pressure profile, left ventricular work index, systolic time ratio and BRS compared to admission. Patients with acute ischemic stroke after a recovery period presented autonomic imbalance and impaired cardiac sympathetic modulation at rest and in response to orthostatic challenge compared to a control group. Furthermore, there was a statistically significant decrease in baroreflex sensitivity, suggesting parasympathetic deficiency.

Cardiovascular and Cutaneous Responses to the Combination of Alcohol and Soft Drinks: The Way to Orthostatic Intolerance?

Aim: Acute ingestion of alcohol is often accompanied by cardiovascular dysregulation, malaise and even syncope. The full hemodynamic and cutaneous responses to the combination of alcohol and sugar (i.e., alcopops), a common combination in young people, and the mechanisms for the propensity to orthostatic intolerance are not well established. Thus, the purpose of this study was to evaluate the cardiovascular and cutaneous responses to alcopops in young subjects.Methods: Cardiovascular and cutaneous responses were assessed in 24 healthy young subjects (12 men, 12 women) sitting comfortably and during prolonged active standing with a 30-min baseline and 130 min following ingestion of 400 mL of either: water, water + 48 g sugar, water + vodka (1.28 mL.kg−1 of body weight, providing 0.4 g alcohol.kg−1), water + sugar + vodka, according to a randomized cross-over design.Results: Compared to alcohol alone, vodka + sugar induced a lower breath alcohol concentration (BrAC), blood pressure and total peripheral resistance (p < 0.05), a higher cardiac output and heart rate (p < 0.05) both in sitting position and during active standing. In sitting position vodka + sugar consumption also led to a greater increase in skin blood flow and hand temperature (p < 0.05) and a decrease in baroreflex sensitivity (p < 0.05). We observed similar results between men and women both in sitting position and during active standing.Conclusion: Despite lower BrAC, ingestion of alcopops induced acute vasodilation and hypotension in sitting position and an encroach of the hemodynamic reserve during active standing. Even if subjects did not feel any signs of syncope these results could be of clinical importance with higher doses of alcohol or if combined to other hypotensive challenges.

Decreased Spontaneous Baroreflex Sensitivity as an Early Marker for Progression of Haemorrhage.

Blood donation provides an ideal setup for assessment of cardiovascular responses to mild hypovolemia for understanding the underlying mechanisms. To evaluate cardiovascular responses in time and magnitude by estimating the spontaneous baroreflex sensitivity (BRS) during and after donation of 450ml of blood. Continuous beat-to-beat blood pressure and lead II ECG was recorded before, during and after blood donation in 54 healthy volunteers (age 34.7 ± 5.08 years; weight 77.9 ± 8.20 kg), followed by offline analyses of baroreflex sensitivity. The systolic, diastolic or mean blood pressures did not change during or after the blood donation. Decrease in pulse pressure and increase in heart rate was observed post donation. The spontaneous BRS decreased during [8.68 (6.038-12.69) ms/mmHg] and after blood donation [9.401 (6.396-11.59) ms/mmHg] as compared to the baseline [12.83 (6.884-18.18) ms/mmHg] with a significant decrease in α-HF on spectral analysis. Mild blood loss (450ml) results in non-hypotensive haemorrhage with a decrease in spontaneous BRS before the rise of heart rate during blood donation.

Baroreflex sensitivity and carotid intima-media thickness in risk stratification of prehypertensives and hypertensives.

BACKGROUNDː The aim of the study was to evaluate the clinical significance of baroreflex sensitivity (BRS) and carotid intima media thickness (IMT) in risk stratification of hypertensives and subjects with high normal blood pressure (SHNBP). METHODSː A total of 20 patients (61±13 years of age, 10 female/10 male) with essential, treated hypertension and 20 subjects (59±8 years of age, 10 female/10 male) with high normal blood pressure were enrolled. The interrelationship between BRS expressed in ms/mmHg (BRS) and IMT of common carotid artery (CCA) in hypertensives and subjects with high normal blood pressure (SHNBP, prehypertensives) was evaluated. BRS was determined by the sequence and spectral method: a five-minute non-invasive beat-to-beat recording of blood pressure (BP) and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. Duplex ultrasonographic examination of the carotid wall and IMT of both CCA and carotid bulb were performed in all patients. RESULTSː Essential hypertension was associated with decreased BRS (r =-0.53, P<0.001). We found out that there was no significant difference between BRS and IMT CCA values in mild treated hypertensives and those in SHNBP. This finding was independent of age-dependent decrease of BRS. SHNBP and hypertensives with critical value BRS≤5 ms/mmHg have significantly increased IMT CCA. CONCLUSIONSː Decreased BRS is an early sign of autonomic dysfunction even in prehypertensive period. SHNBP and hypertensives with BRS≤5ms/mmHg have significantly increased IMT CCA. The principal result of this study showed that BRS and carotid IMT in relatively low-risk hypertensives and SHNBP could identify subjects at higher cardiovascular risk.

Multipotent adult progenitor cells for hypoxic-ischemic injury in the preterm brain.

BackgroundPreterm infants are at risk for hypoxic-ischemic encephalopathy. No therapy exists to treat this brain injury and subsequent long-term sequelae. We have previously shown in a well-established pre-clinical model of global hypoxia-ischemia (HI) that mesenchymal stem cells are a promising candidate for the treatment of hypoxic-ischemic brain injury. In the current study, we investigated the neuroprotective capacity of multipotent adult progenitor cells (MAPC®), which are adherent bone marrow-derived cells of an earlier developmental stage than mesenchymal stem cells and exhibiting more potent anti-inflammatory and regenerative properties.MethodsInstrumented preterm sheep fetuses were subjected to global hypoxia-ischemia by 25 min of umbilical cord occlusion at a gestational age of 106 (term ~147) days. During a 7-day reperfusion period, vital parameters (e.g., blood pressure and heart rate; baroreceptor reflex) and (amplitude-integrated) electroencephalogram were recorded. At the end of the experiment, the preterm brain was studied by histology.ResultsSystemic administration of MAPC therapy reduced the number and duration of seizures and prevented decrease in baroreflex sensitivity after global HI. In addition, MAPC cells prevented HI-induced microglial proliferation in the preterm brain. These anti-inflammatory effects were associated with MAPC-induced prevention of hypomyelination after global HI. Besides attenuation of the cerebral inflammatory response, our findings showed that MAPC cells modulated the peripheral splenic inflammatory response, which has been implicated in the etiology of hypoxic-ischemic injury in the preterm brain.ConclusionsIn a pre-clinical animal model MAPC cell therapy improved the functional and structural outcome of the preterm brain after global HI. Future studies should establish the mechanism and long-term therapeutic effects of neuroprotection established by MAPC cells in the developing preterm brain exposed to HI. Our study may form the basis for future clinical trials, which will evaluate whether MAPC therapy is capable of reducing neurological sequelae in preterm infants with hypoxic-ischemic encephalopathy.

Association of impaired baroreflex sensitivity and increased arterial stiffness in peritoneal dialysis patients.

Peritoneal dialysis patients have high cardiovascular morbidity and mortality. The underlying mechanism of cardiovascular dysfunction remains unclear. Large arterial stiffness in chronic kidney disease (CKD) patients leads to increase in pulse wave velocity (PWV) and decrease in baroreflex sensitivity (BRS). Impairment in baroreflex function could be attributed to the alteration in mechanical properties of large vessels due to arterial remodeling observed in these patients. The present study was designed to study the association of BRS and PWV in peritoneal dialysis (PD) patients. 42 CKD patients (21--without dialysis and 21--on PD) and 25 healthy controls were recruited in this study. BRS was determined by spontaneous sequence method. Short-term heart rate variability (HRV) and blood pressure variability (BPV) were assessed using power spectrum analysis of RR intervals and systolic blood pressure by time domain and frequency domain analysis. Arterial stiffness indices were assessed by carotid-femoral PWV using Sphygmocor Vx device (AtCor Medical, Australia). CKD patients had significantly high PWV and low BRS as compared to healthy controls. PWV had a significant negative correlation with BRS in CKD patients (Spearman r = -0.7049, P < 0.0001; BRS-Systolic BP). On subgroup analysis, PWV was higher with lower BRS in CKD patients on peritoneal dialysis (CKD-PD) as compared to those not on dialysis (CKD-ND). Negative relationship between PWV and BRS was found in both the groups. In addition, BRS was found to have a positive correlation with HRV in CKD patients as well as both the subgroups. Reduction in BRS is strongly associated with increase in PWV in PD patients. Large arterial stiffness probably explains this simultaneous impairment in baroreflex functioning and increase in pulse wave velocity observed in these patients. CKD patients are characterized by poor hemodynamic profile (low BRS, high PWV, and low HRV), and peritoneal dialysis patients had further worsened profile as compared to non-dialysis group.

Eight-year parallel change in baroreflex sensitivity and memory function in a sample of healthy older adults.

To examine whether changes in the cardiac autonomic nervous system (ANS) over time, as expressed by baroreflex sensitivity (BRS), were associated with long-term changes in cognitive performance in elderly individuals without dementia. Community-based 8-year longitudinal study. Clinical settings. Individuals aged 66.9 ± 0.9 (N = 425). At baseline and follow-up, subjects underwent a clinical interview, autonomic and vascular measurements, and a neuropsychological evaluation including attentional, executive, and memory tests using standardized Z-scores. BRS was defined as being normal, moderate, or severe alteration at each evaluation. On the basis of the longitudinal changes subjects were stratified as being stable, moderate or improved. Mean attentional, executive, and memory change Z-scores were -0.41 ± 0.9, -0.15 ± 0.7, and -0.14 ± 0.8, respectively. BRS of 56% of the subjects remained unchanged, of 20% decreased, and of 24% improved. After regression analysis, the worsened BRS group was 1.88 times as likely to have greater memory change as the group with stable BRS (P = .02). No significant association was found between longitudinal change in BRS and attentional and executive changes. In healthy elderly individuals, BRS decrease was associated with a weak but significant decrease in memory function. The long-term effect of BRS on memory changes may suggest a role of the ANS in cognitive decline.

Heart rate complexity in sinoaortic-denervated mice.

What is the central question of this study? New measurements for cardiovascular complexity, such as detrended fluctuation analysis (DFA) and multiscale entropy (MSE), have been shown to predict cardiovascular outcomes. Given that cardiovascular diseases are accompanied by autonomic imbalance and decreased baroreflex sensitivity, the central question is: do baroreceptors contribute to cardiovascular complexity? What is the main finding and its importance? Sinoaortic denervation altered both DFA scaling exponents and MSE, indicating that both short- and long-term mechanisms of complexity are altered in sinoaortic denervated mice, resulting in a loss of physiological complexity. These results suggest that the baroreflex is a key element in the complex structures involved in heart rate variability regulation. Recently, heart rate (HR) oscillations have been recognized as complex behaviours derived from non-linear processes. Physiological complexity theory is based on the idea that healthy systems present high complexity, i.e. non-linear, fractal variability at multiple scales, with long-range correlations. The loss of complexity in heart rate variability (HRV) has been shown to predict adverse cardiovascular outcomes. Based on the idea that most cardiovascular diseases are accompanied by autonomic imbalance and a decrease in baroreflex sensitivity, we hypothesize that the baroreflex plays an important role in complex cardiovascular behaviour. Mice that had been subjected to sinoaortic denervation (SAD) were implanted with catheters in the femoral artery and jugular vein 5 days prior to the experiment. After recording the baseline arterial pressure (AP), pulse interval time series were generated from the intervals between consecutive values of diastolic pressure. The complexity of the HRV was determined using detrended fluctuation analysis and multiscale entropy. The detrended fluctuation analysis α1 scaling exponent (a short-term index) was remarkably decreased in the SAD mice (0.79 ± 0.06 versus 1.13 ± 0.04 for the control mice), whereas SAD slightly increased the α2 scaling exponent (a long-term index; 1.12 ± 0.03 versus 1.04 ± 0.02 for control mice). In the SAD mice, the total multiscale entropy was decreased (13.2 ± 1.3) compared with the control mice (18.9 ± 1.4). In conclusion, fractal and regularity structures of HRV are altered in SAD mice, affecting both short- and long-term mechanisms of complexity, suggesting that the baroreceptors play a considerable role in the complex structure of HRV.

Cardiovascular state changes in simulated work environments.

The usefulness of cardiovascular measures as indicators of changes in cognitive workload has been addressed in several studies. In this paper the question is explored whether cardiovascular patterns in heart rate, blood pressure, baroreflex sensitivity and HRV that are found are consistent within and between two simulated working environments. Two studies, were performed, both with 21 participants: one in an ambulance dispatch simulation and one in a driving simulator. In the ambulance dispatcher task an initial strong increase in blood pressure is followed by a moderate on-going increase in blood pressure during the next hour of task performance. This pattern is accompanied by a strong increase in baroreflex sensitivity while heart rate decreases. In the driving simulator study, blood pressure initially increases but decreases almost to baseline level in the next hour. This pattern is accompanied by a decrease in baroreflex sensitivity, while heart rate decreases. Results of both studies are interpreted in terms of autonomic control (related to both sympathetic and para-sympathetic effects), using a simplified simulation of a baroreflex regulation model. Interpretation of the results leads to the conclusion that the cardiovascular response patterns in both tasks are a combination of an initial defensive reaction, in combination with compensatory blood pressure control. The level of compensatory blood pressure control, however, is quite different for the two tasks. This helps to understand the differences in response patterns between the two studies in this paper and may be helpful as well for understanding differences in cardiovascular response patterns in general. A substantial part of the effects observed during task performance are regulatory effects and are not always directly related to workload manipulations. Making this distinction may also contribute to the understanding of differences in cardiovascular response patterns during cognitive workload.

Cardioprotection afforded by exercise training prior to myocardial infarction is associated with autonomic function improvement.

BackgroundIt has been suggested that exercise training (ET) protects against the pathological remodeling and ventricular dysfunction induced by myocardial infarction (MI). However, it remains unclear whether the positive adjustments on baroreflex and cardiac autonomic modulations promoted by ET may afford a cardioprotective mechanism. The aim of this study was to evaluate the effects of aerobic ET, prior to MI, on cardiac remodeling and function, as well as on baroreflex sensitivity and autonomic modulation in rats.MethodsMale Wistar rats were divided into 4 groups: sedentary rats submitted to Sham surgery (C); trained rats submitted to Sham surgery (TC); sedentary rats submitted to MI (I), trained rats submitted to MI (TI). Sham and MI were performed after ET period. After surgeries, echocardiographic, hemodynamic and autonomic (baroreflex sensitivity, cardiovascular autonomic modulation) evaluations were conducted.ResultsPrior ET prevented an additional decline in exercise capacity in TI group in comparison with I. MI area was not modified by previous ET. ET was able to increase the survival and prevent additional left ventricle dysfunction in TI rats. Although changes in hemodynamic evaluations were not observed, ET prevented the decrease of baroreflex sensitivity, and autonomic dysfunction in TI animals when compared with I animals. Importantly, cardiac improvement was associated with the prevention of cardiac autonomic impairment in studied groups.ConclusionsPrior ET was effective in changing aerobic capacity, left ventricular morphology and function in rats undergoing MI. Furthermore, these cardioprotective effects were associated with attenuated cardiac autonomic dysfunction observed in trained rats. Although these cause-effect relationships can only be inferred, rather than confirmed, our study suggests that positive adaptations of autonomic function by ET can play a vital role in preventing changes associated with cardiovascular disease, particularly in relation to MI.