Changes In Baroreflex Sensitivity Research Articles

Load-Dependent Arterial Stiffness Mechanisms are Responsible for Increased Large Artery Stiffness Observed among Women with a History of Preeclampsia

Introduction: Preeclampsia is a pregnancy complication characterized by hypertension and multi-organ dysfunction and is a leading cause of maternal morbidity and mortality. Preeclampsia results in a two-four fold increased risk of developing hypertension and cardiovascular disease later in life. Large artery stiffness (LAS), a robust risk factor for hypertension and cardiovascular disease, and blood pressure (BP) are elevated after pregnancy in women with a history of preeclampsia (hxPE) and is associated with reduced cardiovagal baroreflex sensitivity (BRS). Whether elevated LAS in women with a hxPE is a consequence of structural remodeling of the arterial wall or the load applied to the arterial wall by the blood (i.e., BP) is unclear. Furthermore, it is unknown whether one or both LAS mechanisms are associated with differences in BRS. Therefore, we hypothesized that 1) structural- and load- dependent LAS would be elevated in women with a hxPE versus no hxPE postpartum controls, and 2) structural- and load- dependent LAS would be associated with BRS in women with hxPE.Methods: LAS was measured via carotid-femoral pulse wave velocity (aortic LAS), and carotid ultrasonography/tonometry (carotid LAS) among 115 women 1-5 years postpartum (age 34 ±4yrs; hxPE n=51; controls n=64). Participant-specific exponential models were used to standardize LAS measurements to a ‘reference’ BP (aortic: 90mmHg mean arterial pressure; carotid: BP 120/80mmHg) and used to calculate structural LAS. Load-dependent LAS was calculated as total minus structural LAS. Spontaneous cardiovagal BRS was measured using the sequence technique. Results: Systolic and diastolic BP were higher in women with hxPE compared with controls (all p<0.001). Aortic, but not carotid, LAS was 0.57 m/s higher in women with hxPE compared with controls (p=0.025). Load-dependent LAS was 0.39 m/s (aortic) and 0.5 m/s (carotid) higher in women with hxPE (p<0.001 for aortic and carotid), but no difference was observed for structural LAS measures (p>0.14 for both). Women with hxPE had 4.13 ms/mmHg lower BRS compared to controls (p=0.042). In women with hxPE, BRS was negatively associated with both aortic and carotid LAS (r=-0.37, p=0.042 and r=-0.38, p=0.025, respectively), and aortic load-dependent LAS (r=-0.39, p=0.033), after adjusting for age and body mass index. Conclusion: Load-dependent LAS mechanisms explained the higher aortic and carotid LAS observed among women with a hxPE and was associated with lower BRS. Our findings suggest that changes in BP and cardiovagal BRS may underpin in part the higher LAS observed in women with a hxPE. Grant funding: American Heart Association 22TPA969732 (to GLP) and 18SCG34350001 (to MKS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences in the age-related decrease of spontaneous baroreflex function in healthy individuals

In this study, we demonstrate that the age-related decrease of spontaneous baroreflex sensitivity is different in men and women by analyzing resting state cardiovascular data of a large sample of healthy individuals.

BaroWavelet: An R-based tool for dynamic baroreflex evaluation through wavelet analysis techniques

Background and objectiveBaroreflex sensitivity constitutes an indicator of the function of the baroreceptor control mechanism of blood pressure levels. It can be computed after estimating heart rate and blood pressure variability. We propose a novel tool for the evaluation of baroreflex sensitivity using wavelet analysis methods. This tool, known as BaroWavelet, incorporates an algorithm proposal based on the analysis methodology of the RHRV software package, as well as other conventional techniques. Our objectives are to develop and evaluate the tool, by testing its ability to detect changes in baroreflex sensitivity in humans. MethodsThe code for this tool was designed in the R programming environment and was organized into two analysis routines and a graphical interface. Simulated recordings of blood pressure and inter-beat intervals were employed for an initial evaluation of the tool in a controlled environment. Finally, similar recordings obtained during supine and orthostatic postural evaluations, from patients that belonged to the open-access EUROBAVAR data set, were analyzed. ResultsBaroWavelet identified the scripted changes of the baroreflex sensitivity in the simulated data. The algorithm proposal was also able to better retain additional information regarding the dynamics of the baroreflex. In the EUROBAVAR subjects, baroreflex sensitivity components were significantly smaller during orthostatism when compared with the supine position. ConclusionsBaroWavelet managed to characterize baroreflex dynamics from the recordings, which were consistent with the findings reported in the literature. This demonstrates its effectiveness to perform these analyses. We suggest that this tool may be of use in research and for the evaluation of baroreflex sensitivity with clinical and therapeutic purposes. The new tool is available at the official GitHub repository of the Autonomic Nervous System Unit of the University of Málaga (https://github.com/CIMES-USNA-UMA/BaroWavelet).

Sympathetic activity is not a main cause of blood pressure reduction with exercise training in un-medicated middle-aged/older men.

This study tested the hypothesis that training reduces resting sympathetic activity and improves baroreflex control in both hypertensive and normotensive men but reduces blood pressure only in hypertensive men. Middle-aged/older un-medicated stage-1 hypertensive males (mean age 55 ± 3 years; n=13) and normotensive controls (mean age 60 ± 5 years; n=12) participated in 8 weeks of supervised high-intensity interval spinning training. Before and after training, muscle sympathetic nerve activity (MSNA) and blood pressure were measured at rest and during a sympatho-excitatory cold pressor test (CPT). Based on the measurements, baroreceptor sensitivity and baroreceptor threshold were calculated. Resting MSNA and baroreceptor sensitivity were similar for the hypertensive and the normotensive groups. Training lowered MSNA (p < 0.05), expressed as burst frequency (burst/min), overall, and to a similar extent, in both groups (17% and 27%, respectively, in hypertensive and normotensive group), whereas blood pressure was only significantly (p < 0.05) lowered (by 4 mmHg in both systolic and diastolic pressure) in the hypertensive group. Training did not (p > 0.05) alter the MSNA or blood pressure response to CPT or increase baroreceptor sensitivity but reduced (p < 0.05) the baroreceptor threshold with a main effect for both groups. Training adherence and intensity were similar in both groups yet absolute maximal oxygen uptake increased by 15% in the normotensive group only. The dissociation between the training induced changes in resting MSNA, lack of change in baroreflex sensitivity and the change in blood pressure, suggests that MSNA is not a main cause of the blood pressure reduction with exercise training in un-medicated middle-aged/older men.

Association between temporal patterns of baroreflex sensitivity after traumatic brain injury and prognosis: a preliminary study

IntroductionTraumatic brain injury (TBI) may lead to an increase in intracranial pressure (ICP) as well as impairment of cerebral vascular reactivity and the autonomic nervous system. This study aimed to investigate individual patterns of changes in baroreflex sensitivity (BRS) along with the assessment of pressure reactivity index (PRx) and ICP after TBI.Materials and methodsTwenty-nine TBI patients with continuous arterial blood pressure (ABP) and ICP monitoring were included. BRS was calculated using the sequential cross-correlation method. PRx was estimated using slow-wave oscillations of ABP and ICP. Outcome was assessed using the Glasgow Outcome Scale.ResultsPooled data analysis of the lower breakpoint during the week that followed TBI revealed that BRS reached a minimum about 2 days after TBI. In patients with good outcome, there was a significant increase in BRS during the 7 days following TBI: rp = 0.21; p = 0.008 and the temporal changes in BRS showed either a “U-shaped” pattern or a gradual increase over time. The BRS value after 1.5 days was found to be a significant predictor of mortality (cut-off BRS = 1.8 ms/mm Hg; AUC = 0.83). In patients with poor outcome, ICP and PRx increased while BRS remained low.ConclusionsWe found an association between temporal patterns of BRS and prognosis in the early days following TBI. Further research in a larger cohort of patients is needed to confirm the weight of these preliminary observations for prediction of prognosis in TBI patients.

Effects of age and sex on vasomotor activity and baroreflex sensitivity during the sleep–wake cycle

Cardiovascular function is related to age, sex, and state of consciousness. We hypothesized that cardiovagal baroreflex sensitivity (BRS) demonstrates different patterns in both sexes before and after 50 years of age and that these patterns are associated with patterned changes during the sleep–wake cycle. We recruited 67 healthy participants (aged 20–79 years; 41 women) and divided them into four age groups: 20–29, 30–49, 50–69, and 70–79 years. All the participants underwent polysomnography and blood pressure measurements. For each participant, we used the average of the arterial pressure variability, heart rate variability (HRV), and BRS parameters during the sleep–wake stages. BRS and HRV parameters were significantly negatively correlated with age. The BRS indexes were significantly lower in the participants aged ≥ 50 years than in those aged < 50 years, and these age-related declines were more apparent during non-rapid eye movement sleep than during wakefulness. Only BRS demonstrated a significantly negative correlation with age in participants ≥ 50 years old. Women exhibited a stronger association than men between BRS and age and an earlier decline in BRS. Changes in BRS varied with age, sex, and consciousness state, each demonstrating a specific pattern. The age of 50 years appeared to be a crucial turning point for sexual dimorphism in BRS. Baroreflex modulation of the cardiovascular system during sleep sensitively delineated the age- and sex-dependent BRS patterns, highlighting the clinical importance of our results. Our findings may aid in screening for neurocardiac abnormalities in apparently healthy individuals.

Coexistence of fibromyalgia syndrome and inflammatory rheumatic diseases, and autonomic cardiovascular system involvement in fibromyalgia syndrome.

The spectrum of symptoms represented by fibromyalgia syndrome (FMS) has a profound effect on daily activities and impairs the quality of life. A considerable proportion of patients with inflammatory rheumatic diseases (IRDs) fulfill the FMS criteria, which can complicate the diagnosis, treatment, and follow-ups of IRD. In addition, the coexistence of FMS may cause unnecessary laboratory and radiological assessments. Several mechanisms have been proposed that may have a role in the etiopathogenesis of FMS, one of which is autonomic dysregulation. In studies evaluating cardiac autonomic dysfunction based on heart rate variability (HRV), there has been found to be a decrease in HRV and dominance of the sympathetic nervous system. Autonomic reactivity reflects modulations of several functions to overcome the existing state and conditions. Blunted autonomic reactivity has been found in some FMS patients, which makes it difficult for these patients to respond appropriately to unexpected stress sources that occur during daily living activities. Baroreceptor signals have an inhibitory influence on the central nervous system, and these impulses cause pain suppression. From this perspective, there are studies that have suggested the involvement of diminished baroreflex sensitivity in the etiology of FMS. The risk of endothelial dysfunction and increased arterial stiffness have been shown to occur in FMS patients due to autonomic dysfunction, sympathetic nervous system dominance, chronic stress, and pain. There is also evidence linking FMS with the risk of atrial and ventricular arrhythmias. Considering all these cardiovascular autonomic dysfunctions, tests that can confirm abnormalities should be performed when suspicion arises. There is a need for specific pharmacological and non-pharmacological treatment alternatives to be identified for subgroups of patients with cardiovascular system abnormalities. Key points • The frequency of FMS accompanying inflammatory rheumatic diseases is considerable and this coexistence leads to troubles in evaluating treatment response and determining appropriate medical treatment options in inflammatory rheumatic diseases. • Various cardiovascular autonomic abnormalities have been described in FMS patients. Among these, the most emphasized are autonomic dysfunction, the disruption of the balance between the sympathetic-parasympathetic nervous systems, blunted autonomic reactivity to acute stress, changes in baroreflex sensitivity, increased arterial stiffness, and electrophysiological alterations. • Autonomic cardiovascular dysfunction may be involved in the complex etiopathogenesis of the fibromyalgia syndrome and may trigger at least some symptoms.

Advanced Cross-Correlation Function Application to Identify Arterial Baroreflex Sensitivity Variations From Healthy to Diabetes Mellitus

Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys, and nerves. DM is of two types–types 1 or 2. In type 1, there is a problem with insulin secretion, and in type 2–insulin resistance. About 463 million people worldwide have diabetes, and 80% of the majority live in low- and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year. Autonomic neuropathy (AN) is one of the common diabetic complications, leading to failure in blood pressure (BP) control and causing cardiovascular disease. Therefore, early detection of AN becomes crucial to optimize treatment. We propose an advanced cross-correlation function (ACCF) between BP and heart rate with suitable threshold parameters to analyze and detect early changes in baroreflex sensitivity (BRS) in DM with AN (DM+). We studied heart rate (HR) and systolic BP responses during tilt in 16 patients with diabetes mellitus only (DM−), 19 diabetes mellitus with autonomic dysfunction (DM+), and 10 healthy subjects. The ACCF analysis revealed that the healthy and DM groups had different filtered percentages of significant maximum cross-correlation function (CCF) value (p < 0.05), and the maximum CCF value after thresholds was significantly reduced during tilt in the DM+ group (p < 0.05). The maximum CCF index, a parameter for the phase between HR and BP, separated the healthy group from the DM groups (p < 0.05). Due to the maximum CCF index in DM groups being located in the positive range and significantly different from healthy ones, it could be speculated that BRS dysfunction in DM and AN could cause a phase change from lead to lag. ACCF could detect and separate DM+ from DM groups. This fact could represent an advantage of the ACCF algorithm. A common cross-correlation analysis was not easy to distinguish between DM− and DM+. This pilot study demonstrates that ACCF analysis with suitable threshold parameters could explore hidden changes in baroreflex control in DM+ and DM−. Furthermore, the superiority of this ACCF algorithm is useful in distinguishing whether AN is present or not in DM.

Autonomic Responses to Acute Hyperoxia are Impaired in Patients with Peripheral Artery Disease

Prior reports suggest that oxidative stress plays an important role in the development of atherosclerotic diseases such as peripheral artery disease (PAD). The effects of acute hyperoxia, an important acute oxidative stressor, on autonomic function have not been well studied in PAD. We hypothesized that the autonomic responses to acute hyperoxia would be impaired in PAD. We studied 17 patients with PAD (12M, 5F, 67 ± 2 yrs) and 15 healthy controls (10M, 5F, 65 ± 2 yrs). The ankle‐brachial indexes in the patients were 0.57 ± 0.03 in the most affected leg and 0.77 ± 0.04 in the less affected leg, respectively. Beat‐by‐beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 min under normoxic resting conditions and during 5‐min hyperoxia (100% oxygen) as an acute oxidative stress test. HR variability (HRV) was calculated and cardiac baroreflex sensitivity (BRS) was estimated with the sequence technique. Under resting conditions, mean HR and mean arterial pressure (MAP) were not significantly different between the groups. Resting values of the root mean square of successive differences between normal heartbeats (RMSSD, a HRV index for parasympathetic activity; 14.1 ± 1.0 vs. 19.8 ± 2.2 ms, P = 0.032) and cardiac BRS (6.43 ± 0.78 vs. 14.86 ± 2.56 ms/mmHg, P = 0.001) were significantly lower in PAD than in healthy controls. Hyperoxia lowered HR in both groups and raised MAP only in patients with PAD. During hyperoxia both HR and MAP were significantly higher in PAD than in controls. Hyperoxia induced an increase in RMSSD and the high frequency (HF) component of HRV (another index for parasympathetic activity) in healthy subjects. However, during hyperoxia no increase in parasympathetic activity was observed in PAD. Both RMSSD and the HF component of the whole trial (i.e. baseline and hyperoxia) in PAD were lower than those in healthy control subjects. Hyperoxia did not induce changes in cardiac BRS in either group, while cardiac BRS of the whole trial in PAD was lower than that in healthy controls. These data suggest that resting parasympathetic activity and cardiac baroreflex function are impaired in PAD. Moreover, the autonomic response to acute oxidative stress (i.e. an increase in parasympathetic activity) is also impaired in PAD. Further studies are needed to examine if antioxidant agents can improve autonomic function in PAD.

Cardiovascular and autonomic profiles in offspring of fructose fed parents: role of anti‐inflammatory cholinergic reflex and exercise training

AimConsidering that anti‐inflammatory cholinergic reflex has been implicated in cardiovascular disorder, and spleen seems to be a critical organ in this reflex, here we evaluated the impact of aerobic exercise training on cardiovascular and autonomic profiles in offspring of rats submitted to fructose overload, as well as, the role of the splenectomy in this condition.MethodsOffspring of Wistar rats treated with fructose or placebo (water) were divided into 5 groups: Sedentary Control (OC), Sedentary Fructose (OF), Trained Fructose (OFT), Splenectomized Sedentary Fructose (OFE) and Splenectomized Trained Fructose (OFST). Fructose overload (10%) was started 30 days after weaning only for the parents and continued until the end of lactation. The offspring received standard feeding and were evaluated 30 days after weaning, at which time the spleen was removed (splenectomy) and the aerobic exercise training was realized on treadmill (1h/d, 5d/week, 4 weeks, moderate intensity). Blood pressure (BP) and heart rate (HR) signals were direct recorded, baroreflex sensitivity (BRS) was measured using increasing doses of phenylephrine and sodium nitroprusside. Oxidative stress was measured in cardiac tissue.ResultsSystolic BP, Diastolic BP and Mean BP increase in OF compared to OC, OFT, OFE and OFST groups (OC: 105±1.3, OF: 112±1.6, OFT: 104±2.4, OFE: 103±3.1, OFST: 104±2 mmHg) HR reduced in the OFT compared to the OC group. Regarding BRS, bradycardic and tachycardic responses were impaired in OF compared to OC group; and OFE, OFT and OFST groups increased these parameters compared to OF group. In the antioxidant profile in cardiac tissue, the activities of catalase and superoxide dismutase were reduced in the OF group compared to the OC group, and increased in the OFE, OFT and OFST groups compared to the OF group. Protein oxidation was increased in the OF group compared to the OC, OFE, OFT and OFST groups (OC: 5.37±0.15, OF: 6.41±0.21, OFT: 4.93±0.3, OFE: 4.94±0.23, OFST: 4.66±0.46 nmol/mg protein). The redox balance of glutathione (GSH/GSSG) was decreased in the OF group compared to the OC and OFT groups.ConclusionThese results demonstrate that fructose exposure in parents induced early changes in offspring BP, BRS and cardiac oxidative stress, that seems to be mediated, at least in part, by the anti‐inflammatory cholinergic reflex. Moreover exercise training seems to prevent/attenuate such dysfunctions.

Sublingual Nitroglycerin Acutely Alters Cardiovagal and Sympathetic Baroreflex Sensitivity in Healthy Humans

Augmented sympathetic nerve activity (SNA) and impaired baroreflex sensitivity (BRS) are important therapeutic targets in patients with cardiovascular diseases. Nitroglycerin (glyceryl trinitrate, GTN) is a vasodilator, widely used in patients with coronary artery diseases, however, the effects of GTN on SNA and BRS are incompletely understood. Importantly, the acute effects of GTN on SNA and BRS are not clear. Additionally, there are no reports evaluating both the sympathetic BRS (SBRS) and cardiovagal BRS (CBRS) responses to the administration of sublingual GTN. The purpose of this study was to assess the acute effects of GTN on muscle sympathetic nerve activity (MSNA), SBRS and CBRS in healthy subjects. We hypothesized that sublingual GTN would rapidly modulate sympathetic and cardiovagal BRS and thus increase MSNA in healthy subjects. Ten (9M, 1F) healthy subjects (60 ± 2 yrs) without medications were examined. Beat-to-beat heart rate (HR), arterial pressure (AP) and MSNA were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated by analyzing the relationship between spontaneous variations in diastolic AP and MSNA. CBRS was assessed with the sequence technique. Every 2 min HR, AP and MSNA data were recorded and compared. SBRS and CBRS were assessed during baseline, and during min 3-6 (Post A) and 7-10 min (Post B) after GTN administration. Compared to baseline, mean AP did not significantly change during Post A (baseline, 98.5 ± 1.8 to 95.6 ± 2.3 mmHg, P = 0.423) but decreased during Post B (91.9 ± 2.2 mmHg, P < 0.05). MSNA increased significantly by min 2 after GTN and remained significantly elevated during both the Post A and Post B periods (31.2 ± 4.0 to 48.2 ± 4.4, and 47.5 ± 4.2; bursts/min, both P < 0.05). Compared to baseline, during the Post A and Post B periods CBRS decreased significantly (12.9 ± 1.6 to 7.1 ± 1.0, and 6.4 ± 0.6; ms･mmHg-1, both P < 0.05), while SBRS increased significantly (0.8 ± 0.2 to 1.5 ± 0.2, and 1.8 ± 0.3; units･beat-1･mmHg-1, both P < 0.05). The SBRS operating point was also reset and shifted to upward during both the Post A and Post B periods. The results show that a clinical sublingual dose of GTN attenuated the CBRS and raised the SBRS with an upward shift of the operating point, resulting in augmented MSNA. Whether these acute changes in MSNA and BRS with GTN in the absence of changes in BP can evoke adverse sequelae in patients with atherosclerosis is unknown. These findings have never been reported before. These factors should be considered by clinicians as they use this agent.

Changes in Heart Rate Variability and Baroreflex Sensitivity During Daytime Naps.

Background and ObjectivesChanges in autonomic cardiac activity during night sleep are well documented. However, there is limited information regarding changes in the autonomic cardiac profile during daytime naps. Heart rate variability (HRV) and baroreflex sensitivity (BRS) are reliable measures of autonomic cardiac activity. The purpose of this study was to determine the changes in HRV and BRS during daytime naps in healthy men.MethodsThis was a cross-sectional study of 25 healthy men. Polysomnographic recording with electrocardiogram monitoring was conducted for all volunteers during a 50–80 min nap between 3.30 pm and 5.30 pm. Five-minute segments during pre-nap wakefulness, non-rapid eye movement (NREM) sleep stages (N1, N2, and N3), rapid eye movement (REM) sleep stage, and post-nap wakefulness were used to measure changes in the variation in HRV parameters, including inter-beat interval (RR-interval), total spectral power (TP), high-frequency power (HF), low-frequency power (LF), and low frequency/high-frequency ratio (LF/HF). BRS was also measured for 10 min during pre- and post-nap wakefulness using finger arterial pressure measurement (Finometer Pro ®).ResultsHRV increased significantly during NREM sleep compared with that during pre-nap wakefulness (p < 0.05), as reflected by RR-interval prolongation, higher HF, and increased HFnu (normalized units). Furthermore, there was a parallel reduction in TP, LF, and LF/HF ratio during NREM sleep, indicating parasympathetic predominance over cardiac autonomic activity. HF and HFnu were significantly reduced during REM sleep compared with that during NREM sleep (p < 0.05). BRS did not show significant differences between pre- and post-nap wakefulness.ConclusionWe observed a progressive increase in parasympathetic activity during daytime sleep as NREM sleep deepened compared with that during wakefulness and REM sleep. Daytime nap may have a favorable cardiovascular impact.

Eight weeks of device-guided slow breathing decreases sympathetic nervous reactivity to stress in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by increased risk for developing hypertension and cardiovascular disease. We recently showed that device-guided slow breathing (DGB) acutely lowers blood pressure (BP) and muscle sympathetic activity (MSNA) and improves baroreflex sensitivity (BRS) in PTSD. The aim of this study was to assess the long-term benefits of DGB on autonomic function at rest and during stress. We hypothesized that long-term DGB improves arterial BRS and lowers BP and MSNA in PTSD. Twenty-five veterans with PTSD were studied and randomized to either 8 wk of daily DGB (n = 12) or 8 wk of sham device (Sham; n = 13). BP, heart rate (HR), and MSNA were measured at rest and during mental math. Arterial BRS was assessed using the modified Oxford technique. Resting MSNA, BP, and heart rate (HR) remained comparable before and after 8 wk in both groups (DGB and Sham). Likewise, the change in sympathetic and cardiovagal BRS was not different between the groups. Interestingly, DGB significantly decreased MSNA reactivity to mental math when expressed as burst frequency (P = 0.012) or burst incidence (P = 0.008) compared with Sham, suggesting a sustained effect of DGB on sympathetic reactivity to stress in PTSD. Contrary to our hypothesis, long-term DGB did not lower systolic BP, diastolic BP, or HR responses to stress compared with Sham. Likewise, pulse pressure reactivity after 8 wk (P = 0.121) was also comparable. In summary, these data suggest that long-term use of DGB may lead to a sustained dampening of sympathetic reactivity to mental stress in PTSD.

Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria.

Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. Individuals with type 1 diabetes (n=54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. Mean age±sd was 60±10years and diabetes duration was 38±14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P=0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.

Autonomic Dysfunction in Women with Androgen Excess PCOS

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrinopathy, affecting approximately 10% of reproductive age women. Further, 75% of women with PCOS have the more severe phenotype, Androgen Excess‐PCOS (AE‐PCOS), that is dominated by clinical and biochemical manifestations of hyperandrogenism. AE‐PCOS is also associated with elevated blood pressure (BP), which we hypothesized is the result of androgen‐associated impairments in autonomic function. Thus, we tested the hypothesis that androgen excess is associated with impaired baroreflex sensitivity (BRS) in women with AE‐PCOS. We tested four obese women with AE‐PCOS (age 30±3 y; BMI 39±11 kg/m2) at 0, HDT, ‐20, ‐30 lower body negative pressure (LBNP) under three conditions: Baseline (BL), during hormone suppression with a GnRH antagonist (GnRH ant, 7 days, 250 μg/day), and with GnRH ant+testosterone (T, 4 days, 5 mg/day). Women were mildly hypertensive at rest at BL, but BP increased following hormone suppression with the GnRH ant and remained elevated with T (93±7, 105±5, 105±9 mm Hg for BL, GnRH ant, and T, respectively, P=0.02). Blood pressure was well maintained during LBNP under the three hormone conditions. Forearm vascular resistance (FVR) increased during LBNP under each condition, but the increase was greatest during GnRH ant and T (Δ54±19, Δ235±145, Δ104±64 units for BL, GnRH ant, and T, respectively, P=0.04). The resulting BRS slopes were greater in GnRH ant (−5.2 units/mm Hg) compared to BL (−1.6 units/mm Hg), demonstrating concomitant testosterone and estrogen suppression improved BRS in women with AE‐PCOS. When we restored androgens, the BRS slope was again attenuated (T= −1.7 units/mm Hg), suggesting an important role for androgens in autonomic function in AE‐PCOS. GnRH ant increased resting BP independent of T in AE‐PCOS, which is likely a function of the continued estrogen suppression. Thus, hypertension associated with AE‐PCOS appears closely associated with estrogen suppression and independent of testosterone‐induced changes in BRS. In summary, both estrogens and androgens contribute to BP regulation in women with AE‐PCOS. Women with AE‐PCOS frequently present with mild hypertension that is driven by altered estrogen and testosterone exposures. Treating hypertension is crucial for preventing cardiovascular disease in this vulnerable population.Support or Funding InformationR01 HL135089

Long‐term Device Guided Slow Breathing Decreases Sympathetic Nervous Reactivity to Stress in Post‐Traumatic Stress Disorder

Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. We recently showed that device‐guided slow breathing (DGB), in which breathing rates are lowered to subphysiologic levels using a biofeedback device, acutely lowers blood pressure (BP) and muscle sympathetic activity (MSNA) and improves sympathetic baroreflex sensitivity (BRS) in post‐traumatic stress disorder (PTSD). The aim of this study was to assess the potential long‐term benefits of DGB on MSNA, hemodynamics, and BRS in patients with PTSD at rest and during stress. We hypothesized that long‐term DGB will further improve sympathetic BRS, lower BP and MSNA in PTSD. Twenty five young adults, clinically diagnosed with PTSD, were studied and randomized to either 8 weeks of DGB (n=12; age, 36±2 years; BMI, 30±2 Kg/m2) or 8 weeks of an identically looking Sham device (n=13; age, 34±2 years; BMI, 28±2 Kg/m2). DGB guided the participants to a breathing rate of 5–6 breaths/min while Sham guided breathing to 14 breaths/min. BP, heart rate (HR) and MSNA was measured at rest and during 3 min of mental arithmetic. Sympathetic and cardiovagal BRS were assessed using the modified oxford technique. Measurements were done during two laboratory visits, before and after 8 weeks of 15 min of at‐home breathing daily. Both groups (DGB and Sham) were matched for age, BMI, resting MSNA, BP and heart rate (HR). Resting MSNA, BP and HR remain comparable (condition*device, p&gt;0.05) before and after the 8 weeks (condition effect) in both breathing groups. Likewise, the change in sympathetic and cardiovagal BRS was not different between the two groups (condition*device, p&gt;0.05). Interestingly, 8 weeks of DGB significantly decreased minute by minute (time effect) MSNA reactivity to mental arithmetic when expressed as burst frequency (time*condition*device, p= 0.006) or burst incidence (time*condition*device, p= 0.004) compared to 8 weeks of sham, suggesting a sustained effect of chronic DGB on sympathetic reactivity to mental stress in PTSD. Contrary to our hypothesis, long term DGB did not lower (time*condition*device, p&gt;0.05) systolic BP, diastolic BP or HR responses to stress compared to sham. However, DGB but not sham tended to decrease pulse pressure reactivity after 8 weeks of intervention (time*condition*device, p= 0.06), due to the tendency for low systolic BP reactivity post DBG. In summary, our data suggest that the long‐term use of DGB leads to a sustained dampening of sympathetic reactivity and trend towards improved pulse pressure reactivity to mental stress. Taken together, these results suggest that long term use of DGB may have beneficial effects on neurocardiovascular reactivity in individuals with PTSD.Support or Funding InformationThis work was supported by National Institutes of Health (NIH) Grant R01 HL135183; NIH R61 AT010457, VA Merit I01CX001065, the Department of Veterans Affairs, Veterans Health Administration and the Office of Research and Development, Decatur, Georgia.

Effects of Short‐term Warm Water Bathing on Cardiac Baroreflex Sensitivity in Healthy Men

Bath‐related fatal (sudden cardiac arrest) and non‐fatal accident (dizziness and disturbance of consciousness) have been reported frequently in Japan. Cardiac baroreflex sensitivity (BRS) may relate to these symptoms. However, underlying mechanism(s) is poorly understood. With this information as background, we determined the effects of short‐term warm water immersion on cardiac BRS in healthy men. Twelve apparent healthy men underwent the single sit‐stand test (e.g., 5‐min sitting on the floor of bathtub and then standing up and remained standing for 5 min quietly) twice (e.g., without and with 41 °C warm water at the heart level). Beat‐to‐beat blood pressure was continuously recorded through the protocol (via Finometer). BRS was evaluated by the sequence method from heart rate response to the standing‐induced abrupt drop of mean arterial pressure (MAP). Additionally, after the each test, brachial‐ankle pulse wave velocity (baPWV: an index of arterial stiffness) was measured in the supine position. During the bathing, heart rate and cardiac output (estimated by Modelflow method) were significantly increased but MAP, stroke volume, total peripheral resistance, and tympanic temperature did not change significantly (vs. pre‐bathing). Regarding the single sit‐stand test, there were no significant changes in the baseline (sitting) MAP (from 73±16 to 77±16 mmHg, P=0.322) and the standing‐induced decreases in MAP (from −33±12 to −33±13 mmHg, P=0.970) between pre‐ and post‐bathing, but MAP‐HR slope was blunted after the bathing (from −0.47±0.26 to −0.35±0.25 bpm/mmHg, P=0.024, Figure 1). The baPWV was significantly decreased after the bathing (vs. pre‐bathing (from 12.2±1.2 to 11.8±1.2 m/sec, P=0.002). Change in MAP‐HR slope correlated with corresponding change in baPWV (r=0.610, P=0.036, Figure 2). Our results indicate that: (1) even a short‐term warm water bathing deteriorates cardiac BRS although it did not induce greater orthostatic hypotension, and (2) the change in cardiac BRS with the short‐term bathing is associated with the change in arterial stiffness. Further study to determine the impact of prolonged warm water bathing is needed.Support or Funding InformationThis study was supported by Japan Health &amp; Research Institute Research Grant.Cardiac barorefex sensitivity (BRS) gain and brachial‐ankle pulse wave velocity (baPWV) before and after 5‐min warm‐water bathing. Data are mean and SD. Thin lines indicate individual data.Figure 1Relationship between 5‐min bathing induced changes in baPWV and cardiac BRS gain.Figure 2

Sympathetic Overactivation From Supine to Upright Is Associated With Orthostatic Hypertension in Children and Adolescents.

There are no prior publications or submissions with any overlapping information, including studies and patients. The study data have not been presented as an abstract or poster before the submission.Objectives: The study was conducted to analyze the changes of baroreflex sensitivity and heart rate variability from supine to upright standing in children and adolescents with orthostatic hypertension to explore whether and how the autonomic nerve regulation was involved in the development of pediatric orthostatic hypertension.Methods: This case-control study included twenty-five children with orthostatic hypertension (the patient group) and twenty-six healthy controls (the control group). All subjects underwent a standing test, during which their hemodynamic parameters were continuously monitored by a Finapres Medical System, and baroreflex sensitivity and heart rate variability were calculated.Results: The demographic characteristics, supine baroreflex sensitivity, and supine heart rate variability including time domain and frequency domain indices did not differ between the patients with orthostatic hypertension and healthy subjects (P > 0.05). However, a more obvious drop of baroreflex sensitivity and a greater increase of low frequency/high frequency ratio from supine to upright were observed in subjects with orthostatic hypertension compared with those in the healthy children (P < 0.001 and P < 0.01, respectively). Changes of baroreflex sensitivity were negatively related to mean arterial pressure changes from supine to upright in all subjects (P < 0.01), and the increases in low frequency/high frequency ratio from supine to standing were positively correlated with those in mean arterial pressure in the study subjects (P < 0.001).Conclusion: Upright sympathetic overactivation is associated with pediatric orthostatic hypertension.

Heart to breathe: partial ablation of rostral ventrolateral medulla catecholaminergic neurons mediates disordered breathing in volume overload heart failure rats

Heart to breathe: partial ablation of rostral ventrolateral medulla catecholaminergic neurons mediates disordered breathing in volume overload heart failure rats

Baroreflex Sensitivity Predicts Response to Metoprolol in Children With Vasovagal Syncope: A Pilot Study.

Objective: To explore the role of baroreflex sensitivity (BRS) in the head-up tilt test (HUTT) in predicting the therapeutic response of vasovagal syncope (VVS) patients to metoprolol.Materials and Methods: Vasovagal syncope patients treated with metoprolol were enrolled in this study and were classified as responders or non-responders according to changes in their symptom scores before and after metoprolol treatment. Values of BRS in the supine position and at positive response occurrence in the HUTT were obtained, and BRS changes from supine to positive response occurrence were calculated. Differences between responders and non-responders were analyzed. Receiver operating characteristic curve analysis was performed to assess the value of BRS for predicting the therapeutic efficacy of metoprolol in pediatric patients with VVS.Results: Forty patients (14 boys; 11.8 ± 2.5 years) diagnosed with VVS were recruited in the study, 28 of whom were verified to be responders to metoprolol and 12 of whom were verified as non-responders. They did not show any differences in baseline characteristics and hemodynamics in the HUTT (p > 0.05). However, the responders had an obviously increased supine BRS value compared to the non-responders (16.9 ± 7.7 ms/mmHg vs. 7.6 ± 3.8 ms/mmHg; p < 0.01). No difference in BRS at positive response occurrence was observed between the two groups (8.9 ± 8.5 ms/mmHg vs. 10.6 ± 9.8 ms/mmHg; p > 0.05). Accordingly, the changes in the BRS of responders were more obvious than in non-responders (8.0 ± 7.8 ms/mmHg vs. −3.0 ± 10.4 ms/mmHg; p < 0.01). The area under the receiver operating characteristic curve for the predictive value of supine BRS was 0.887 (95% CI, 0.779–0.995; p < 0.01). A cut-off value of 10 ms/mmHg yielded a sensitivity and specificity of 82 and 83%, respectively, in predicting the therapeutic efficacy of metoprolol in pediatric VVS patients. The area under the receiver operating characteristic curve for the predictive value of BRS changes was 0.827 (95% CI, 0.693–0.962; p < 0.01). A cut-off value of 4 ms/mmHg yielded a sensitivity and specificity of 71 and 83%, respectively.Conclusion: Baroreflex sensitivity may predict the response of children with VVS to metoprolol.