Measure Of Baroreflex Sensitivity Research Articles

Investigating the effects of artificial baroreflex stimulation on pain perception: A comparative study in no-pain and chronic low back pain individuals.

The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, where acute pain triggers ANS responses, whereas resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by 'top-down' processes occurring in the brain, brainstem and spinal cord, known as 'descending modulation'. By employing the conditioned pain modulation (CPM) paradigm, we previously revealed a connection between reduced low-frequency heart rate variability and CPM. Individuals with chronic pain often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and heart rate variability regulation, may play a significant role in this relationship, although their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In the present study, we combined artificial 'baroreceptor stimulation' in both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. In total, 22 individuals with chronic low back pain (CLBP) and 29 individuals with no-pain (NP) took part in the present study. We identified a differential modulation of baroreceptor stimulation on pressure pain between the groups of NP and CLBP participants. Specifically, NP participants perceived less pain in response to baroreflex activation, whereas CLBP participants exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex sensitivity in both CLBP and NP participants. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the ANS and descending pain modulation. KEY POINTS: Baroreflex stimulation has different effects on pressure pain in participants with chronic pain compared to matched individuals with no-pain. Baroreceptor activation decreases pain in participants with no-pain but increases pain perception in participants with chronic pain. Baroreflex sensitivity is associated with conditioned pain modulation in both groups of chronic pain and no-pain participants. The reactivity of the baroreflex during autonomic stress demonstrated a positive correlation with Pain Trait scores in participants with chronic back pain.

Blood pressure variability at rest and during pressor challenges in patients with acute ischemic stroke.

Patients with acute ischemic stroke (AIS) have elevated blood pressure (BP) variability (BPV) and reduced baroreflex sensitivity (BRS) at rest for several days after initial stroke symptoms. We aimed to assess BPV and BRS in AIS patients during pressor challenge maneuvers in the acute and subacute phases of stroke. Pressor challenge maneuvers simulate day-to-day activities and can predict the quality of life. Continuous beat-to-beat BP and ECG in 15 AIS patients (mean age 69 ± 7.5 years) and 15 healthy controls (57 ± 16 years) were recorded at rest and during a 5-min rapid head positioning (RHP) paradigm. Patients were assessed within 24 h (acute phase) and 7 days (subacute phase) of stroke onset. Low frequency (LF) SBP power (measure of BPV), LF-α, and combined α-index (measure of BRS) were calculated from the recordings. In the acute phase, at rest, LF-SBP power was higher ( P = 0.024) and α-index was lower ( P = 0.006) in AIS patients than in healthy controls. There was no change in LF-SBP during RHP in the patients but in healthy controls, it increased significantly ( P = 0.018). In the subacute phase, at rest, the alpha-index increased ( P = 0.037) and LF-SBP decreased ( P = 0.029) significantly in the AIS patients, however, there was still no rise in the LF-SBP power during RHP ( P = 0.240). AIS patients have a high resting BPV. High resting BPV may be responsible for blunted BPV responses during pressor challenge maneuvers such as RHP, suggesting ongoing autonomic dysfunction and compromised quality of life.

Reduced resting beat-to-beat blood pressure variability in females with relapsing-remitting multiple sclerosis

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease of the central nervous system and cardiovascular autonomic dysfunction has been well documented in this population. The sympathetic nervous system contributes to beat-to-beat blood pressure regulation primarily by baroreflex control of the peripheral vasculature which may be impaired in females with RRMS. Even at rest, attenuated sympathetic control of vasomotor tone may result in large and frequent blood pressure excursions (i.e., greater blood pressure variability). Therefore, the primary purpose of this investigation was to test the following hypotheses; (1) females with RRMS have augmented beat-to-beat blood pressure variability compared to healthy controls and (2) reduced sympathetic baroreflex sensitivity in females with RRMS is related to augmented blood pressure variability. MethodsElectrocardiogram and beat-to-beat blood pressure were continuously recorded during 8–10 min of supine rest in 26 females with clinically definite RRMS and 24 sex-, age- and BMI- matched healthy controls. Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (MS, n = 15; CON, n = 14). Traditional statistical measurements of dispersions were used to index beat-to-beat blood pressure variability. Spontaneous sympathetic baroreflex sensitivity was quantified by sorting diastolic blood pressures into 3 mmHg bins and calculating MSNA burst incidence within each bin. Weighted linear regression was then used to account for the number of cardiac cycles in each bin and calculate slopes. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method. ResultsGroups had similar resting mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), MSNA burst frequency and MSNA burst incidence (All P > 0.05). The standard deviation and interquartile range of MAP, SBP and DBP were less in females with RRMS compared to healthy controls (All P < 0.05). There were no between groups differences in sympathetic baroreflex sensitivity or cardiac baroreflex sensitivity (Both P > 0.05) and baroreflex sensitivity measures were not related to any indices of blood pressure variability (Both P > 0.05). ConclusionThese data suggest that females with RRMS have reduced beat-to-beat blood pressure variability. However, this does not appear to be related to changes in sympathetic or cardiac baroreflex sensitivity.

Correlation between Cardiovascular Autonomic and Pulmonary Ventilation Functions in Myasthenia Gravis Patients.

This study aimed to investigate the relationship between pulmonary function and cardiac autonomic function parameters in clinically stable myasthenia gravis (MG) patients. A total of 22 MG patients and 22 healthy controls (HCs) were evaluated. Pulmonary function test parameters, heart rate variability (HRV), baroreflex sensitivity (BRS), and cardiovascular autonomic function test parameters (the Valsalva ratio, expiration/inspiration (E/I) ratio) were assessed. Compared with the HCs, the patients demonstrated a similar diffusion capacity for carbon monoxide (DLCO); a lower forced vital capacity (FVC%pred); a lower forced expiratory volume in 1 s (FEV1%pred); lower BRS and HRV, including high-frequency and total power spectral density; and a higher percentage of abnormal cardiovagal function test results (p < 0.05). A lower BRS in the patient group was associated with worse clinical disease outcomes and reduced pulmonary function (DLCO%pred, R = 0.59; TLC%pred, R = 0.48). Age, forced vital capacity, and total lung capacity predicted the E/I ratio (R2 values ranging from 0.48 to 0.49). Our study demonstrated a significant relationship between a reduced pulmonary ventilation function and respiratory mechanics with cardiovascular autonomic parameters, including the E/I ratio, BRS, and HRV measures at rest, as shown in the MG group. Future studies should focus on the interplay between respiratory and autonomic function testing, as well as pulmonary rehabilitation, to mitigate cardiovascular risk in these patients.

ARTERIAL BAROREFLEX FUNCTION IS IMPAIRED DURING THE RECOVERY FROM ACUTE LUNG INJURY IN A BLEOMYCIN-INDUCED RAT LUNG INJURY MODEL

Objective: Acute lung injury (ALI) and its clinical correlate, the acute respiratory distress syndrome (ARDS), results due, in part, to disruption of the normal capillary endothelial barrier and invokes perturbations of ventilatory control. ALI is associated with autonomic dysfunction and cardiac arrhythmias. In a recent study we suggested that rats were susceptible to cardiac arrhythmia even during the recovery from ALI, in part, due to abnormalities in cardiac sympathetic ganglia. On the other hand, if arterial baroreflex function is altered during the recovery of ALI remains unknown. The primary goal of this study was to examine baroreflex function during the recovery stage from ALI in a bleomycin (Bleo)-induced rat ALI model. Design and method: ALI was induced in male SD rats (200-250g) using a single intra-tracheal injection of Bleo (2.5 mg/kg). 4 weeks post Bleo (n = 7) or saline (sham, n = 6), rats were anesthetized with urethane (800 mg/kg ip) and alpha-chloralose (40 mg/kg ip) to measure baroreflex sensitivity. Baroreflex curves were generated by measuring the heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to decreases and increases in mean blood pressure (MAP) by intravenous administration of nitroglycerin (25 μg) followed by phenylephrine (10 μg). Differences between sham and Bleo rats were determined by one-way ANOVA followed by the Tukey post hoc test. Results: Compared to sham rats, there was a significant decrease in the RSNA (117.4±11.6 vs. 77.5±8.9 %baseline, P = 0.018) or HR (147.5±9.7 vs. 75.1±11.3 bpm, P&lt;0.001) range in Bleo rats. Minimum RSNA or HR was also decreased in bleo rats compared to sham rats. There was no significant difference in either the slope coefficient or the blood pressure at the midpoint of the range (BP50) between the two groups. There was a significant decrease in peak slope [or maximum gain (Gainmax) in Bleo rats (MAP-RSNA Gainmax: 3.11±0.27 vs. 1.74±0.31, p = 0.017; MAP-HR Gainmax: 3.57±0.31 vs. 1.21±0.14, p&lt;0.001). Conclusions: Our data demonstrate impaired baroreflex function during the recovery state from ALI. Autonomic dysfunction may also contribute to increased cardiovascular risk during the recovery stage from ALI.

The Year in Hungarian Cardiology 2022: Heart failure and cardiomyopathies

In the year 2022 a large number of remarkable scientific papers were published in the field of heart failure and heart muscle disease, to which the Hungarian Heart Failure community contributed with influential scientific activity. Results of landmark randomized clinical trials were published, and in recognition of the clinical and scientific activity of the Hungarian centers, notable activity was also demonstrated publishing these studies. In the field of cardiomyopathies several novel results were published in 2022. In connection with hypertrophic cardiomyopathy (HCM) a landmark paper described the genetic architecture of the affected Hungarian population. An editorial comment was published in a highly ranked journal describing the myosin motor inhibition concept. An interesting paper about a retrospective analysis of cardiac amyloidosis patients, and MR specific differences between left ventricular noncompaction and dilated cardiomyopathy was published. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was an ongoing pandemic in 2022 resulting in millions of deaths worldwide, affecting the heart of as much as 20–25% of those infected and causing several cardiac complications. Studies were published about the screening for myocardial injury and about the immunological response on disease itself and the vaccination against the virus. A joint scientific statement by the ESC also dealt with this topic. An impressive study was published about the prognostic value of anemia in patients with preserved, and mildly reduced and recovered ejection fraction and about the feasibility of baroreflex sensitivity measurements in heart failure subjects. In relation to drug therapy, a study is also worth mentioning about the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines, and a network meta-analysis of randomized trials, analyzing the cardiovascular outcomes in patients treated with gliflozins. Finally, a focused issue of Cardiologia Hungarica on heart failure and myocardial diseases should be highlighted.

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.

Baroreceptor Sensitivity in Individuals with CKD and Heart Failure.

Heart failure is the most common cardiovascular complication of chronic kidney disease (CKD) and foreshadows a high morbidity and mortality rate. Baroreflex impairment likely contributes to cardiovascular mortality. We aimed to study the associations between CKD, heart failure, and baroreflex sensitivity (BRS) and their association with cardiovascular outcomes. We retrospectively analyzed data from a cohort of 247 individuals with moderate to severe HF. All subjects underwent BRS measurements after intravenous phenylephrine along with electrocardiography, echocardiography, and laboratory measurements. We used logistic regression models to assess the association of CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m2) with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality. Median eGFR among individuals with CKD was 52 (IQR 44-56) ml/min per 1.73 m2. eGFR was lower in those with depressed BRS (65 [IQR 54-76] ml/min per 1.73 m2) compared with those with preserved BRS (73 [IQR 64-87] ml/min per 1.73 m2; P≤0.001). The majority of individuals with CKD had depressed BRS compared with those without CKD (60% versus 29%; P=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared with those with preserved BRS and CKD. Cardiac BRS is depressed in patients with mild to moderate CKD and HF and associated with cardiovascular mortality. Additional study to confirm its contribution to cardiovascular mortality, particularly in advanced CKD, is warranted.

Effect of acute hyperglycemia on baroreflex sensitivity in healthy young adults.

Autonomic dysfunction, impaired baroreflex sensitivity (BRS), and deranged circulatory homeostasis have been observed in chronic hyperglycemia and found to be associated with increased cardiovascular morbidity and mortality. However, the acute effects of hyperglycemia in healthy subjects have been rarely studied. The present study explores the effect of acute hyperglycemia on conventional and unconventional parameters of BRS in healthy young adults. For the estimation of BRS beat-to-beat blood pressure (BP) and electrocardiogram were recorded in forty-two young, healthy subjects during fasting and at 1hr of the oral glucose load. Analysis of BRS was carried out by sequence and spectral method. Number of UP-, DOWN- and ALL-sequences between ramps of BP and RR-interval were calculated as an unconventional measure of BRS along with the other conventional parameters. We observed significant alteration of unconventional parameters of autonomic functions [the number of sequences of UP- (p = 0.0039) and ALL-sequences (p = 0.0233) of systolic BP and RR interval; and, UP- (p = 0.0380), DOWN- (p = 0.0417) and ALL-sequences (p = 0.0313) of mean BP and RR- interval] during acute hyperglycemia as compared to the fasting state. However, no significant changes were observed in any of the conventional parameters of BRS during acute hyperglycemia as compared to the fasting state. Present study concludes that the unconventional parameters of BRS - the number of sequences between the ramp of BP and RR-interval - change significantly during acute hyperglycemia. However, the conventional parameters do not show significant changes during acute hyperglycemia. We may hypothesize that the relatively constant BRS is maintained at the expense of increased oscillations in the ramp of BP and RR-interval.

Cardiac Autonomic Function Following Bilateral and Unilateral Upper Body Acute Resistance Exercise.

The purpose of this study was to compare cardiac autonomic responses following bilateral and unilateral upper-body (UB) acute resistance exercise (ARE). In total, 14 individuals were assessed for markers of cardiac autonomic responses via heart rate variability (HRV) and baroreflex sensitivity (BRS) at rest and at 10- and 30-min following ARE. Logarithmically transformed (ln) HRV measures included: total power (ln TP), high-frequency power (ln HF power), low-frequency power (ln LF power), sympathovagal balance (ln LF: HF), and the square root of the mean squared differences of successive R-R intervals (ln RMSSD). BRS was assessed using the sequence method. Two-way repeated measures ANOVAs were used to analyze effects of UB ARE (bilateral, unilateral) across time (Rest, 10, and 30 min). There were no significant (p > 0.05) interactions. However, there were significant (p ≤ 0.05) main effects of time such that ln TP, ln HF power, ln RMSSD, and BRS decreased and did not recover within 30 min compared to Rest for both conditions. Collectively, this study suggests that bilateral and unilateral UB ARE yielded similar reductions, for at least 30 min, in respect to vagal measures of HRV and BRS.

The feasibility of baroreflex sensitivity measurements in heart failure subjects: The role of slow-patterned breathing.

Increased muscle sympathetic nerve activity (MSNA) indicates an adverse outcome in heart failure. Decreased baroreflex modulation of MSNA is a well-known feature of the disease. The determinability of cardiovagal baroreflex sensitivity (BRS) in heart failure is low, however, the determinability of sympathetic BRS is not known. We have assessed the spontaneous, MSNA burst incidence-based baroreflex index (BRSsymp) in 33 stable heart failure patients and in 10 healthy controls using the traditional r ≥ .5 cutoff for acceptable individual diastolic pressure-burst incidence slopes, and also a more stringent r ≥ .7 cutoff. We have also assessed the influence of 6/min breathing. The determinability of BRSsymp in heart failure patients was 64% during spontaneous breathing with r ≥ .5 cutoff, and 39% using the r ≥ .7 cutoff. The determinability of these indices further decreased during 6/min breathing, dropping to 29% with the r ≥ .7 cutoff. In contrast, the determinability of the cardiovagal BRS indices increased significantly with 6/min breathing (from 24% to 66%; p < .001). Patients who still had determinable BRSsymp at the r ≥ .7 cutoff had a significantly lower baseline burst incidence than those with an undeterminable index (70 ± 14 vs. 89 ± 10 burst/100 cycles; p < .002). Neither the 6/min breathing, nor the r ≥ .7 cutoff limit influenced the high availability of BRSsymp in healthy subjects. The determinability of BRSsymp in heart failure patients is limited, especially with the 0.7 limit for correlation. Undeterminable BRSsymp in patients is associated with higher sympathetic activity. 6/min breathing improves the determinability of cardiovagal BRS indices, but not that of BRSsymp.

Effects of the number of sit-stand maneuver repetitions on baroreflex sensitivity and cardiovascular risk assessments.

Sit-stand maneuvers (SSMs) have increasingly been used for baroreflex sensitivity (BRS) measurement in physiological research, but it remains unknown as to how many SSMs need to be performed to measure BRS and assess its relationship with cardiovascular disease (CVD) risk. Therefore, this study aimed to determine 1) the effect of the number of SSM repetitions on BRS, and 2) the association between BRS and CVD risk factors. Data were collected from 174 individuals during 5 min of spontaneous rest and 5 min of repeated SSMs at 0.05 Hz (i.e., 15 cycles of 10-s sit and 10-s stand). During SSMs, BRS was calculated from the incremental cycles of 3, 6, 9, 12, and 15 SSMs using transfer function analysis of heart rate (HR) and systolic blood pressure (SBP). General CVD risk factors, carotid arterial stiffness, and cardiorespiratory fitness were measured. In result, HR and SBP increased during SSMs (P < 0.05). The BRS remained at a similar level during the resting and SSM conditions, whereas the coherence function reached its peak after 3 cycles of SSMs. BRS with ≥6 cycles of SSMs was strongly correlated with age (r = -0.721 to -0.740), carotid distensibility (r = 0.625-0.629), and cardiorespiratory fitness (r = 0.333-0.351) (all P < 0.001). Multiple regression analysis demonstrated that BRS with ≥6 cycles of SSMs explained >60% of the variance in CVD risk factors. Therefore, our findings suggest that repeated SSMs significantly strengthens the association between BRS and CVD risk factors. Particularly, BRS with ≥6 cycles of SSMs is strongly associated with CVD risk.

Effect of various exercise training interventions on cardiac autonomic function in obese individuals: A systematic review and meta-analysis

The aim of the systematic review and meta-analysis was to investigate the effect of various exercise training interventions on cardiac autonomic function (CAF) in obese. We conducted electronic database search from SCOPUS, PubMed, Web of science and cochrane library from inception till August 2021. Among 3234 articles retrieved, 9 were found to be eligible for the present review. Studies investigating the effect of exercise interventions on CAF assessed either by linear or non-linear measures of heart rate variability (HRV), baroreflex sensitivity, or heart rate recovery were included. Of the studies retrieved, 9 were included in the systematic review. Meta-analysis was conducted on 5 studies. The findings of the qualitative analysis revealed low to moderate certainty of evidence for aerobic exercise (AE) while low to very low was documented for combined training (CT). Standardized mean differences (SMD) showed a large effect of AE on SD of normal to normal (N–N) intervals (SDNN) [SMD 1.35, 95% confidence interval (CI) −0.11, 2.81; p = 0.07] and root mean square of successive differences between adjacent inter-beat (R-R) intervals (RMSSD) [SMD 1.50, 95% confidence interval (CI) 0.12, 2.88; p = 0.03]. CT depicted moderate insignificant change in low-frequency power of HRV (LF; SMD −0.55, 95% CI −1.52, −0.42; p = 0.27). This systematic analysis revealed positive effect of exercise training on CAF in obese individuals. AE and CT have large and moderate impact on CAF respectively though the pooled result was insignificant for majority of the variables, while effect of HIIT and RT yet remains to be fully elucidated. • Obesity is strongly linked with the development of cardiac autonomic dysfunction. • Exercise training improves markers of cardiac autonomic function in obese. • Aerobic exercise has large impact on linear and non linear indices of heart rate variability. • In future, trials focusing on high intensity interval training and resistance training must be conducted.

Determinants of orthostatic cerebral oxygenation assessed using near-infrared spectroscopy.

To understand the relationship between blood pressure changes during standing up and clinical outcome, cerebral oxygenation needs to be measured, which may be performed using near-infrared spectroscopy (NIRS). However, the role of potential determinants of NIRS-derived orthostatic cerebral oxygenation, i.e., age, sex, type of postural change (i.e., standing up from sitting versus supine position), blood pressure (BP) and baroreflex sensitivity (BRS) is still unknown and needed to better interpret findings from studies using orthostatic NIRS measurements. 34 younger (median age 25years, inter quartile range (IQR) 22-45) and 31 older adults (median age 77years, IQR 72-81) underwent BP, BRS and NIRS measurements during standing up from sitting and supine position. Linear regression models were used to assess the potential determinant role of age, sex, type of postural change, BP and BRS in orthostatic cerebral oxygenation drop and recovery. Orthostatic cerebral oxygenation test-retest reliability was assessed using intra class correlations. Younger age, male sex and standing up from supine compared to sitting position were positively associated with cerebral oxygenation drop; older age and standing up from sitting compared to supine position were associated with higher cerebral oxygenation recovery. Test-retest reliability was highest (ICC>0.83) during standing up from supine position. Based on the findings of this study, age, sex and type of postural change are significant determinants of NIRS-derived orthostatic cerebral oxygenation and should be taken into account in the interpretation of NIRS measurements. In the design of new studies, standing up from supine position is preferable (higher reliability) over standing up from sitting position.

Androgenic modulation of arterial baroreceptor dysfunction and neuroinflammation in endotoxic male rats

Autonomic neuropathy contributes to cardiovascular derangements induced by endotoxemia. In this communication, we tested the hypothesis that androgenic hormones improve arterial baroreflex dysfunction and predisposing neuroinflammatory response caused by endotoxemia in male rats. Baroreflex curves relating changes in heart rate to increases or decreases in blood pressure evoked by phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious sham-operated, castrated, and testosterone-replaced castrated rats treated with or without lipopolysaccharide (LPS, 10 mg/kg i.v.). Slopes of baroreflex curves were taken as measures of baroreflex sensitivity (BRS). In sham rats, LPS significantly reduced reflex bradycardia (BRSPE) and tachycardia (BRSSNP) and increased immunohistochemical expression of nuclear factor kappa B (NFκB) in heart and brainstem neurons of nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM). The baroreflex depressant effect of LPS was maintained in castrated rats despite the remarkably attenuated inflammatory response. Testosterone replacement of castrated rats counteracted LPS-evoked BRSPE, but not BRSSNP, depression and increased cardiac, but not neuronal, NFκB expression. We also evaluated whether LPS responses could be affected following pharmacologic inhibition of androgenic biosynthetic pathways. Whereas none of LPS effects were altered in rats pretreated with formestane (aromatase inhibitor) or finasteride (5α-reductase inhibitor), the LPS-evoked BRSPE, but not BRSSNP, depression and cardiac and neuronal inflammation disappeared in rats pretreated with degarelix (gonadotropin-releasing hormone receptor blocker). Overall, despite the seemingly provocative role for the hypothalamic-pituitary–gonadal axis in the neuroinflammatory and baroreflex depressant effects of LPS, testosterone appears to distinctly modulate the two LPS effects.

Autonomic Nervous System Activity during Refractory Rise in Intracranial Pressure.

Refractory intracranial hypertension (RIH) is a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment. Recent reports suggest that the autonomic nervous system (ANS) activity may be altered during changes in ICP. Our study aimed to assess ANS activity during RIH and the causal relationship between rising in ICP and autonomic activity. We reviewed retrospectively 24 multicenter (Cambridge, Tromso, Berlin) patients in whom RIH developed as a pre-terminal event after acute brain injury (ABI). They were monitored with ICP, arterial blood pressure (ABP), and electrocardiography (ECG) using ICM+ software. Parameters reflecting autonomic activity were computed in time and frequency domain through the measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS). Our results demonstrated that a rise in ICP was associated to a significant rise in HRV and BRS with a higher significance level in the high-frequency HRV (p < 0.001). This increase was followed by a significant decrease in HRV and BRS above the upper-breakpoint of ICP where ICP pulse-amplitude starts to decrease whereas the mean ICP continues to rise. Temporality measured with a Granger test suggests a causal relationship from ICP to ANS. The above results suggest that a rise in ICP interacts with ANS activity, mainly interfacing with the parasympathetic-system. The ANS seems to react to the rise in ICP with a response possibly focused on maintaining the cerebrovascular homeostasis. This happens until the critical threshold of ICP is reached above which the ANS variables collapse, probably because of low perfusion of the brain and the central autonomic network.

Methodological Consideration on Monitoring Refractory Intracranial Hypertension and Autonomic Nervous System Activity.

Refractory intracranial hypertension (RIH) refers to a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment and leads to patient death. Detrimental sequelae of raised ICP in acute brain injury (ABI) are unclear because the underlying physiopathological mechanisms of raised ICP have not been sufficiently investigated. Recent reports have shown that autonomic activity is altered during changes in ICP. The aim of our study was to evaluate the feasibility of assessing autonomic activity during RIH with our adopted methodology. We selected 24 ABI patients for retrospective review who developed RIH. They were monitored based on ICP, arterial blood pressure, and electrocardiogram using ICM+ software. Secondary parameters reflecting autonomic activity were computed in time and frequency domains through the continuous measurement of heart rate variability and baroreflex sensitivity. The results of the analysis will be presented later in a full paper. This preliminary analysis shows the feasibility of the adopted methodology.

Prone sleeping affects cardiovascular control in preterm infants in NICU.

Prone sleeping is used in preterm infants undergoing intensive care to improve respiratory function, but evidence suggests that this position may compromise autonomic cardiovascular control. To test this hypothesis, this study assessed the effects of the prone sleeping position on cardiovascular control in preterm infants undergoing intensive care treatment during early postnatal life. Fifty-six preterm infants, divided into extremely preterm (gestational age (GA) 24-28 weeks, n = 23) and very preterm (GA 29-34 weeks, n = 33) groups, were studied weekly for 3 weeks in prone and supine positions, during quiet and active sleep. Heart rate (HR) and non-invasive blood pressure (BP) were recorded and autonomic measures of HR variability (HRV), BP variability (BPV), and baroreflex sensitivity (BRS) using frequency analysis in low (LF) and high (HF) bands were assessed. During the first 3 weeks, prone sleeping increased HR, reduced BRS, and increased HF BPV compared to supine. LF and HF HRV were also lower prone compared to supine in very preterm infants. Extremely preterm infants had the lowest HRV and BRS measures, and the highest HF BPV. Prone sleeping dampens cardiovascular control in early postnatal life in preterm infants, having potential implications for BP regulation in infants undergoing intensive care.

High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) improves symptoms and autonomic function for insomnia: A randomized, placebo-controlled clinical trial.

IntroductionEffective insomnia interventions that also address autonomic dysregulation are lacking. We evaluate high‐resolution, relational, resonance‐based, electroencephalic mirroring (HIRREM®), in a randomized, controlled clinical trial. HIRREM is a noninvasive, closed‐loop, allostatic, acoustic stimulation neurotechnology, to support self‐optimization of brain rhythms.MethodsOne hundred and seven adults (mean age 45.7, SD ± 5.6, 73 women), with Insomnia Severity Index (ISI) scores of ≥15, received ten, 90‐min sessions of HIRREM, with tones linked to brainwaves (LB, 56), or random tones not linked to brainwaves (NL, 51), as an active, sham placebo. Outcomes were obtained at enrollment (V1), 1–7 days (V2), 8–10 weeks (V3), and 16–18 weeks (V4) after intervention. Primary outcome was differential change in ISI from V1 to V3. Secondary measures assessed depression (BDI), anxiety (BAI), quality of life (EQ‐5D), and a sleep diary. Ten minute recordings of HR and BP allowed analysis of heart rate variability (HRV) and baroreflex sensitivity (BRS).ResultsOf 107 randomized, 101 completed the intervention. Intention‐to‐treat analysis (107) of change from V1 to V3 revealed a mean reduction of ISI in NL of −4.93 (SE ± 0.76) points, with additional, significant reduction of −2.05 points (0.74) in LB (total reduction of −6.98, p = .045). Additional reduction of −2.30 points (0.76) was still present in the LB at V4 (p = .058). Total ISI reduction from V1 to V4 was −5.90 points for NL and −7.93 points in LB. There were group differences (p < .05) for multiple HRV and BRS measures (rMSSD, SDNN, HF alpha, and Seq ALL), as well as total sleep time, sleep onset latency, and sleep efficiency. There were no serious adverse events.ConclusionsResults of this controlled clinical trial showed clinically relevant reduction of insomnia symptoms with HIRREM, over, and above an active, sham control, with associated, durable improvement in autonomic cardiovascular regulation.

Abstract P198: Vitamin D Supplementation Improves Autonomic Response To Head Up Tilt In Adolescents Suffering From Orthostatic Intolerance

Background: We have previously shown in a group of adolescents who are suffering from orthostatic intolerance (OI) and syncope that they exhibited impairment in autonomic function in supine position and greater loss of baroreflex sensitivity (BRS) and heart rate variability (HRV) measures upon head up tilt (HUT). They also had low vitamin D level that correlated with the severity of symptoms on tilt. In this pilot study we hypothesized that vitamin D supplementation to normal levels will improve the autonomic response to change in position. Methods: In a pilot group of eight female adolescents (mean age= 16.0 years) who are vitamin D deficient, head up tilt was done at baseline and after two months of vitamin D supplementation (2000-5000 IU daily based on baseline level). Heart rate, blood pressure, BRS measured as Sequence Up (parasympathetic) and Sequence down (sympathetic), HRV measured as SDNN and rMSSD, and sympathovagal balance (LF/HF ratio) were assessed both in supine and HUT positions. Results: As shown in the table, compared to baseline, vitamin D supplementation improved vitamin D level, minutes standing on tilt, BRS, HRV and sympathovagal balance measures at baseline and reduced the loss in BRS and HRV measures upon standing. There were no changes in blood pressure measures between pre and post treatment. Conclusions: Vitamin D supplementation for two months restored vitamin D to normal levels and was associated with improvement in the hemodynamic response to standing. These data provide evidence of potential therapeutic benefit of vitamin D supplementation for patients suffering from orthostatic intolerance who are vitamin D deficient,