Baroreflex Sensitivity In Patients Research Articles

Spontaneous Sympathetic Baroreflex Sensitivity Is Impaired in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have chronic overactivation of the sympathetic nervous system that contributes to hypertension and increased cardiovascular risk. The sympathetic baroreflex is a major regulator of sympathetic activity in response to changes in blood pressure; however, limited information is available regarding sympathetic baroreflex control in non-dialysis patients with CKD. In the present study we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) is attenuated in non-dialysis patients with CKD. In 17 sedentary patients with CKD stages III-IV (76% hypertensive and 29% with diabetes) [12 male/5 female, age: 57 ± 13 yr, 13 Black/4 White, systolic/diastolic BP: 122 ± 17/75 ± 7 mmHg, BMI: 31 ± 5 kg/m2, eGFR: 40 ± 14 mL/min/1.73m2] and 9 controls (CON) (89% hypertensive and 22% with diabetes) [7 male/2 female, age: 51 ± 13 yr, 8 Black/1 White, systolic/diastolic BP: 123 ± 6/79 ± 6 mmHg, BMI: 30 ± 6 kg/m2, eGFR: 95 ± 12 mL/min/1.73m2], resting beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography) were continuously recorded during 10 min of semi-recumbent rest. Weighted linear regression analysis between MSNA burst incidence and diastolic blood pressure was used to determine the spontaneous sympathetic baroreflex sensitivity (sBRS). Resting MSNA burst incidence was higher in patients with CKD [CKD: 70 ± 19 bursts (100 heart beats)−1. mmHg−1 versus CON: 47 ± 9 bursts (100 heart beats)−1. mmHg−1; p<0.001], and a higher MSNA burst frequency was observed in CKD (CKD: 43 ± 11 bursts. min−1 versus CON: 32 ± 10 bursts. min−1; P=0.021], whereas resting mean arterial blood pressure (91 ± 9 mmHg versus 94 ± 5 mmHg; P=0.317) and heart rate were similar between groups. Patients with CKD had reduced sBRS compared to controls [CKD: -1.37 ± 0.59 bursts (100 heart beats)−1 mmHg−1 versus CON: -2.79 ± 1.33 bursts (100 heart beats)−1 mmHg−1; P=0.013]. The MSNA burst incidence (r = -0.63, p<0.001) and the sBRS (r = -0.57, P=0.002) were significantly associated with the estimated glomerular filtration rate (eGFR). Overall, these preliminary findings suggest an attenuated sympathetic baroreflex sensitivity in patients with CKD compared with age and-comorbidities matched controls, with greater impairment in those with more severe kidney dysfunction. This work was supported by National Institutes of Health Grants R01HL135183 and R61AT010457 (J.P). 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.

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH.Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal.Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50–67). WFNS scale was 2 (1–4) and the modified Fisher scale was 3 (1–3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (Rp = −0.42; p < 0.001).Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

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.

Impairment in Baroreflex Sensitivity in Recent-Onset Type 2 Diabetes Without Progression Over 5 Years.

Impaired baroreflex sensitivity (BRS) predicts cardiovascular mortality and is prevalent in long-term diabetes. We determined spontaneous BRS in patients with recent-onset diabetes and its temporal sequence over 5 years by recording beat-to-beat blood pressure and R-R intervals over 10 min. Four time domain and four frequency domain BRS indices were computed in participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 206/381) and age-matched glucose-tolerant control subjects (control 1/control 2: n = 65/83) and subsets of consecutive participants with type 1/type 2 diabetes who reached the 5-year follow-up (n = 84/137). Insulin sensitivity (M-value) was determined using a hyperinsulinemic-euglycemic clamp. After appropriate adjustment, three frequency domain BRS indices were reduced in type 2 diabetes compared with control 2 and were positively associated with the M-value and inversely associated with fasting glucose and HbA1c (P < 0.05), whereas BRS was preserved in type 1 diabetes. After 5 years, a decrease in one and four BRS indices was observed in patients with type 1 and type 2 diabetes, respectively (P < 0.05), which was explained by the physiologic age-dependent decline. Unlike patients with well-controlled recent-onset type 1 diabetes, those with type 2 diabetes show early baroreflex dysfunction, likely due to insulin resistance and hyperglycemia, albeit without progression over 5 years.

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.

Expression of α7 Nicotinic ACh Receptors in Blood Mononuclear Cells: Correlation with Impaired Baroreflex Sensitivity in Patients with Heart Failure

Autonomic imbalance, including depleted parasympathetic drive, is a fundamental pathophysiological feature of heart failure (HF). In clinical studies, parasympathetic withdrawal is assessed using arterial baroreflex sensitivity (BRS). Parasympathetic activity can also be tracked based on the assessment of molecular elements of cholinergic signaling in target cells. Hence, we investigated whether BRS is associated with the mRNA expression of nicotinic cholinergic receptors (α7nAChR) in peripheral blood mononuclear cells (PBMCs) in subjects with and without HF. We examined 39 patients with stable systolic HF (35 men, 4 women, age 56 ± 13 years, left ventricular ejection fraction, LVEF, 30 ± 9%) and 17 healthy subjects (6 men, 11 women, age 60 ± 11 years, LVEF 64 ± 9%). BRS was assessed using a phenylephrine test. Relative transcript levels of α7nAChRs in PBMCs were analyzed using a real-time PCR. Patients with HF, as compared to healthy subjects, demonstrated much higher expression of α7nAChR mRNA in PBMCs (4.4 ± 2.2 vs. 1.4 ± 2.2 AU; P 0.2). In a combined sampling including subjects with and without HF, BRS negatively correlated with the content of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = –0.43, P < 0.05). In such sampling, α7nAChR expression in PBMCs also negatively correlated with LVEF (r = –0.39, P < 0.05) and was positively associated with plasma NT-proBNP (r = 0.38, P < 0.01), but without associations with other clinical and laboratory measures. Expression of α7nAChRs in PMBCs is inversely correlated with BRS (r = –0.50, P < 0.01). Thus, autonomic imbalance confirmed by physiological tests is accompanied by increased expression of α7 nicotinic receptors on circulating immune cells.

Chronic obstructive pulmonary disease-induced autonomic dysfunction may be associated with cerebral blood flow regulation and brain function.

Chronic obstructive pulmonary disease (COPD) increases the risk of cerebrovascular disease and brain dysfunction, such as ischaemic stroke and dementia, in proportion to its severity. Cerebral blood flow (CBF) regulation may be a key factor for this phenomenon, but the physiological mechanisms of COPD pathogenesis regarding cerebrovascular disease are yet to be established. Physiologically, COPD is a chronic hypoxic condition, and long-term oxygen therapy improves survival in patients with COPD and severe resting hypoxaemia. Given this background, Hoiland et al. (2018) have reported, in this issue of Experimental Physiology, the effects of oxygen therapy on cerebral oxygen delivery and neurovascular function in patients with COPD. The authors demonstrated that oxygen therapy improved cerebral oxygen delivery by increasing peripheral oxyhaemoglobin saturation () and enhanced neurovascular function in patients with COPD. These findings suggested that such oxygen delivery and functional neurovascular improvements may provide a physiological link between oxygen therapy and the reduced risk of cerebrovascular disease in patients with COPD. Thus, oxygen therapy appears beneficial for patients with COPD. On the contrary, oxygen therapy did not alter volumetric global CBF (Hoiland et al., 2018), suggesting that the cerebral vasculature has a low sensitivity to the acute normalization of . From these results, it can be suspected that the contribution of CBF regulation to COPD-induced cerebrovascular disease or brain dysfunction is likely to be minimal. In patients with COPD receiving oxygen therapy, we should consider cerebral oxygen delivery and cerebral haemodynamics and other physiological mechanisms potentially induced by hypoxaemia to understand the physiological mechanisms of this positive phenomenon. One example includes autonomic dysfunction, which is commonly observed in patients with COPD. Indeed, a previous study (van Gestel, Kohler, & Clarenbach, 2012) has demonstrated that autonomic dysfunction through sympathetic nervous system overactivity might contribute to the initiation and progression of cardiovascular disease in the examined population. However, the contributions of autonomic dysfunction to COPD-induced cerebrovascular disease and brain dysfunction may not be simple, because autonomic dysfunction modifies cerebral vasculature regulation (cerebral autoregulation and cerebral CO2 reactivity), the arterial baroreflex and the respiratory system (Ogoh & Ainslie, 2009). Indeed, baroreflex function is attenuated in patients with COPD. Importantly, the baroreflex simultaneously influences the respiratory system (ventilation and tidal volume) and the control of arterial pressure (Brunner, Sussman, Greene, Kallman, & Shoukas, 1982). Moreover, there is an interaction between cerebral vasculature regulation and the arterial baroreflex or respiratory system (Ogoh & Ainslie, 2009). Taken together, we cannot rule out the possibility that autonomic dysfunction might affect cerebral vasculature and function in the examined population both directly and indirectly. Indeed, another study (Bartels, Gonzalez, Kim, & De Meersman, 2000) demonstrated that oxygen therapy increased baroreflex sensitivity in patients with COPD, indicating that oxygen supplementation in this population significantly and favourably altered autonomic activity. Thus, oxygen therapy-modified autonomic function may be associated with improved survival in patients with COPD. Regarding this concept, the duration or severity of COPD may cause different functional autonomic adaptations and may result in different effects of oxygen therapy on the cerebral vasculature. The work of Hoiland et al. (2018) has clearly described the mechanisms through which oxygen therapy improved survival in patients with COPD. However, in order to identify the mechanisms underlying these effects, we should conduct additional, detailed investigations of the physiological regulatory mechanisms associated with various autonomic functions.

Baroreflex Sensitivity in Patients with Intractable Generalized Tonic Clonic Seizures versus Partial Seizures (P2.259)

Baroreflex Sensitivity in Patients with Intractable Generalized Tonic Clonic Seizures versus Partial Seizures (P2.259)

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease

Objectives: Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS.Materials and methods: We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery.Results: Integrated BRS was reduced in patients [7.00 (5.80–9.25) vs. 11.1 (8.50–14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54 ± 1.20 vs. 4.48 ± 1.43 ms/10−3). FMD was higher in patients (9.81 ± 3.77 vs. 5.59 ± 1.36%). FMD and neural BRS were directly related in controls (r = 0.62), but inversely related in patients (r = –0.49).Conclusions: Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.

Effect of spinal manipulative treatment on cardiovascular autonomic control in patients with acute low back pain

BackgroundThis study aimed to quantify the effect of spinal manipulative treatment (SMT) from an analysis of baroreflex, systolic blood pressure and heart rate variability (HRV) on patients with acute back pain. It was hypothesized that SMT would increase the parasympathetic cardiovascular autonomic control.MethodsTwenty-two patients with acute back pain were randomly divided into two groups: one receiving sham treatment (Sham) and the other receiving SMT. Recordings were completed during the first day and the seventh day, immediately before and after treatment on both days. ECG and systolic blood pressure were continuously recorded to compute cardiovascular variability and baroreflex sensitivity components. The perceived level of pain was measured with the numeric pain scale (NPS) 48 h before, just before and just after each treatment. The NPS ranged from 0 to 100% (peak of pain before treatment). ECG and systolic blood pressure recordings were analyzed in time frequency domain using the Smoothed pseudo Wigner-Ville distribution.ResultsRoot mean square of the successive differences, high frequency power of the heart rate variability, and high frequency baroreflex sensitivity differences between post and pre tests were higher in the SMT group than in the Sham group (p < 0.01), whereas no differences were observed with the other heart rate variability components. Also, no differences were observed with the systolic blood pressure components. Although the estimated pain scale values decreased over time, no difference was observed between the SMT and Sham groups.ConclusionsThis seems to be the first study to assess the effect of SMT on both heart rate variability and baroreflex sensitivity in patients with acute back pain. SMT can be seen to provoke an increase in parasympathetic control known to relate to a person’s healthy state. Thus, cardiovascular variability analysis may be a useful tool for clinicians to quantify and objectify the beneficial effects of spinal manipulation treatment.

Exercise individualized by TRIMPi method reduces arterial stiffness in early onset type 2 diabetic patients: A randomized controlled trial with aerobic interval training

BackgroundArterial stiffness (AS) and baroreflex sensitivity (BRS) are subclinical markers of vascular diseases in type 2 diabetes (T2D). We evaluated the effects of aerobic interval training (AIT), with loads prescribed according to individual heart rate and lactate profiling obtained during a baseline treadmill test (TRIMPi method), on AS and BRS in patients with early-onset T2D without cardiovascular complications. Population study and methodsTwenty-two sedentary overweight T2D patients (aged 57±7years) were randomized to 12-weeks open-label of supervised AIT by TRIMPi (n=8) or unsupervised physical activity as per usual care (SOC) (n=11). Following parameters were evaluated (pre- and post-): anthropometrics; six-minute walking test (6MWT); fasting glucose, insulin, HbA1c; Pulse Wave Velocity (PWV) and Augmentation Index (AIxHR75) using radial approach (SphigmoCor System); BRS using Finapress method. ResultsBoth interventions significantly improved distance walked during 6MWT (AIT 52±21m; SOC 39±24m, p<0.001 for both). PWV significantly improved with AIT (p<0.001) whereas did not vary with SOC (p=0.47). Similar trend was observed for AIxHR75. Resulting percent changes from baseline were significantly better for AIT vs SOC, in both PWV (−15.8±2.1 vs +1.50±3.4%, p<0.001) and AIxHR75 (−28.9±3.2% vs +12.7±2.4%, p<0.001). BRS similarly improved in both groups (p<0.001 for both), as well as body weight, HbA1c and blood pressure. ConclusionIn sedentary T2D patients, 12-weeks AIT individualized by TRIMPi method improved AS to a greater extent than usual recommendation on physical activity, whilst exerting comparable effects on exercise capacity, glycemic control and body weight. Further researches are needed to ascertain durability of these effects.

Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis.

Key points Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality.Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known.In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls.Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity.The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age‐ and sex‐matched RA‐normotensive (n = 13), RA‐hypertensive patients (RA‐HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C‐reactive protein (hs‐CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA‐HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min–1) compared to NC (22 ± 9 bursts min–1; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA‐HTN and HTN patients [5(3–8), 4 (2–7), 6 (4–9) ms mmHg–1] compared to NC [11 (8–15) ms mmHg–1; P = 0.002]. HR was independently associated with hs‐CRP. Increased MSNA and reduced cBRS were associated with hs‐CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events.

Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study

Autonomic regulation therapy (ART) with chronic vagus nerve stimulation improves ventricular function in patients with chronic heart failure, but its effects on quantitative T-wave alternans (TWA), ventricular tachycardia (VT), baroreflex sensitivity, and autonomic tone remained unknown. Effects on TWA, a marker of risk of life-threatening arrhythmias; heart rate turbulence (HRT), an indicator of baroreflex sensitivity; heart rate variability; and VT incidence were studied in 25 patients with chronic symptomatic heart failure and reduced ejection fraction enrolled in the ANTHEM-HF study (NCT01823887). Twenty-four-hour ambulatory electrocardiographic recordings made before ART system (Cyberonics, Inc., Houston, TX) implantation involving the left or right vagus nerve and after 6 and 12 months of chronic therapy (10-Hz frequency, 250-μs pulse width, maximum tolerable current amplitude after 10 weeks of titration) at low-intensity (<2 mA; n = 10, 40%) or high-intensity (≥2 mA; n = 15, 60%) stimulation levels were analyzed. At 12 months, peak TWA levels were reduced by 29% from 71.0 ± 4.6 to 50.5 ± 1.8 μV (P < .0001). The number of patients with severely abnormal TWA (≥60 μV) was reduced by 76% from 17 to 4 (P < .0005), and the number of patients with nonsustained VT decreased by 73% from 11 to 3 (P < .025). HRT slope (P < .025), high frequency heart rate variability (HRV) (P = .05), and square root of the mean squared differences of successive normal-to-normal interval HRV (P = .013) increased. The mean heart rate derived from 24-hour Holter electrocardiograms decreased by 10% from 77 ± 2 to 69 ± 2 beats/min (P = .0002). HRT onset was unchanged. Chronic ART in patients with symptomatic heart failure improves cardiac electrical stability, as reflected by reduced TWA levels and heart rate, suppresses VT, and increases baroreceptor sensitivity. These observations deserve study in a larger population.

Improvement of baroreflex sensitivity in patients with obstructive sleep apnea following surgical treatment

ObjectiveDepressed baroreflex sensitivity (BRS) have been reported in patients with obstructive sleep apnea (OSA). This study aimed to determine if surgery can improve the clinical outcomes by investigating changes in BRS and in other cardiovascular autonomic parameters. MethodsEighty-one OSA patients were enrolled. They were classified as mild OSA if their apnea–hypopnea index (AHI) was 5–15, moderate OSA if their AHI was 15–30, and sever OSA if their AHI was >30. Twenty-three subjects with AHI<5 were recruited as controls. For patients who received surgery, polysomnography (PSG) and autonomic tests were evaluated upon enrollment and six-months after surgery. ResultsThe patient number for mild, moderate, and severe OSA was 22, 22, and 37, respectively. BRS on enrollment showed significant difference among the four groups, with the highest BRS in the control group, follow by the mild, moderate, and severe OSA groups. There were significant correlations between BRS and all PSG parameters. The depressed BRS significantly improved after surgery. ConclusionsSurgical modifications of the upper airways can improve the depressed BRS in OSA patients. SignificanceThe study offers the promise that surgical treatment for OSA not only improves the index of PSG, but also reduces the possibility of cardiovascular risk.

Effect of Hypoxia on Baroreflex Control of Blood Pressure During Hypoglycemia in Type 1 Diabetes Mellitus

Objective Patients with Type 1 Diabetes Mellitus (T1DM) exhibit impaired baroreflex sensitivity (BRS) which is worsened during hypoglycemia and can be improved with hyperoxia. These data support a contribution of hypoxia to impairments in BRS in T1DM. Given the prevalence of both nocturnal hypoglycemia and sleep disordered breathing in this population, we sought to examine the combined effect of hypoglycemia and hypoxia on BRS. We hypothesized the fall in BRS with hypoglycemia in patients with T1DM would be further reduced when combined with hypoxia. Methods Subjects with T1DM (n=13) completed two 180-minute hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 µmol/mL) clamps separated by a minimum of 1 week and randomized to normoxia (SaO2 ~98%) or hypoxia (SaO2 ~85%). Heart rate (ECG) and blood pressure (finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of spontaneous cardiac BRS (sCBRS). Results Hypoglycemia resulted in significant reductions in sCBRS when compared with baseline levels (Main effect of hypoglycemia: ms/mmHg, p=0.01; beat/min/mmHg, p=0.19). sCBRS was further impaired during hypoxia (Main effect of hypoxia: ms/mmHg, p=0.03; beat/min/mmHg, p=0.05). Conclusions Acute hypoxia worsens hypoglycemia-mediated impairments in BRS in patients with T1DM. These results highlight the potential cumulative dangers of hypoglycemia and hypoxia in this vulnerable population. Research Support: NIH DK090541, Dutch Heart Foundation

Reduced baroreflex sensitivity in patients with vasovagal syncope.

The evidence is conflicting regarding the role of baroreflex in patients with vasovagal syncope. The aim of the study was to measure baroreflex sensitivity (BRS) and hemodynamic parameters during head up tilt test (HUT) with nitroglycerine stimulation. Nitroglycerine stimulated HUT was performed in 51 patients with the history of recurrent syncope (mean age 46±19 years, 18 men, 23 women). Cardiac output (CO), stroke volume (SV), left-ventricular ejection time (LVET) and total peripheral resistance (TPR) were assessed during HUT by volume-clamp method using a beat-to-beat photopletysmography. Spontaneous BRS sensitivity was computed using a sequential BRS calculation. HUT was positive after nitroglycerine administration in 28 patients and negative in 23 patients. BRS was lower at the time of syncope in HUT positive group compared to end-test values in HUT negative group (0.54±0.27 vs 0.72±0.35, p=0.03). At the time of syncope, CO was significantly lower in HUT positive patients compared to HUT negative patients (2.6±1.4 vs 4.3±1.4 l/min, p<0.0001), similarly as SV (34.7±14.7 vs 49.2±19 ml, p=0.005). LVET was significantly higher in syncopal patients (282.27±26.2 vs 240.5±58.8 ms, p=0.002) and TPR did not differ between two groups. Reduced BRS may contribute to the development of the vasovagal syncope by inability to adequately counteract hypotension resulting from decreased cardiac output at the time of syncope (Tab. 3, Ref. 18).

Device‐guided slow deep breathing in essential hypertension: is cardiac or sympathetic baroreflex sensitivity altered? (1132.7)

The influence of device‐guided slow deep breathing (SDB; RESPeRATE□) on arterial baroreflex control of the heart and muscle sympathetic nerve activity (MSNA) in essential hypertension patients remains unclear. To address this, respiratory rate, partial pressure of end‐tidal carbon dioxide (PETCO2), MSNA (microneurography), heart rate (HR) and blood pressure (BP: Finometer) were monitored in 8 hypertensive patients (55±14 years, BMI 28±3 kg/m2, 152±26/71±11 mmHg [systolic/diastolic BP], duration of hypertension 6.4±6.7 years; mean±SD) during 10 min of normal breathing and 10 min of SDB. Cardiac baroreflex sensitivity (sequence technique) and spontaneous arterial baroreflex control of MSNA burst incidence were calculated offline. As expected, SDB decreased respiratory rate (13±4 to 6±1 breath/min, P=0.001), whereas PETCO2 (P=0.22), and mean BP (98±14 to 97±13 mmHg, P=0.11) were unchanged. MSNA burst incidence tended to fall during SDB (median with interquartile range from 46 [34‐56] to 40 [31‐48] bursts per 100 heart beats, P=0.12), however neither cardiac nor sympathetic baroreflex sensitivity were altered (P&gt;0.05). In conclusion, acute device‐guided SDB does not appear to modify cardiac and sympathetic baroreflex sensitivity in patients with essential hypertension.Grant Funding Source: Supported by British Heart Foundation

Treadmill gait training improves baroreflex sensitivity in Parkinson’s disease

Partial weight supported treadmill gait training (PWSTT) is widely used in rehabilitation of gait in patient with Parkinson’s Diseases (PD). However, its effect on blood pressure variability (BPV) and baroreflex sensitivity (BRS) in PD has not been studied. To evaluate the effect of conventional and treadmill gait training on BPV components and BRS. Sixty patients with idiopathic PD were randomized into three groups. Twenty patients in control group were on only stable medication, 20 patients in conventional gait training (CGT) group (Stable medication with CGT) and 20 patients in PWSTT group (Stable medication with 20 % PWSTT). The CGT and PWSTT sessions were given for 30 min per day, 4 days per week, for 4 weeks (16 sessions). Groups were evaluated in their best ‘ON’ states. The beat-to-beat finger blood pressure (BP) was recorded for 10 min using a Finometer instrument (Finapres Medical Systems, The Netherlands). BPV and BRS results were derived from artifact-free 5-min segments using Nevrocard software. BRS showed a significant group with time interaction (F = 6.930; p = 0.003). Post-hoc analysis revealed that PWSTT group showed significant improvement in BRS (p < 0.001) after 4 weeks of training. No significant differences found in BPV parameters; systolic BP, diastolic BP, co-variance of systolic BP and low frequency component of systolic BP. Four weeks of PWSTT significantly improves BRS in patients with PD. It can be considered as a non-invasive method of influencing BRS for prevention of orthostatic BP fall in patients with PD.

Preliminary analysis on perioperative baroreflex sensitivity in patients with hypertension

Objective To analyze perioperative baroreflex sensitivity (BRS) in patients with hypertention and the autonomic nerve activity.Methods Blood pressure and heart rate before and after injection nitroglycerin were measured in patients with hypertension or without (n=48 including 24 undergoing treatment patients).BRS was calculated according to Robert formula.Results BRS Baseline(3.3±2.0) and BRS intraoperative(1.7±1.1) in patients with hypertension were obviously lower than those in non-hypertension patients [(5.7±4.1),(3.3±3.1) respectively,P＜0.01].BRS Baseline (2.1±1.3),BRS intraoperative (1.5±0.9)and BRS postoperative (1.4±1.3) in patients without treatment were lower than those in patients undergoing treatment [(5.3±1.8),(2.0±1.8),(1.8±1.2) respectively,P＜0.01].Conclusions The perioperative autonomic nerve function is significantly impaired in patients with hypertension.And the impaired autonomic can be improved by treatment. Key words: Hypertension; Perioperative; Baroreflex sensitivity

Psychophysiology of perceived effort during physical tasks

Arterial stiffness (AS) and baroreflex sensitivity (BRS) are subclinical markers of vascular diseases in type 2 diabetes (T2D). We evaluated the effects of aerobic interval training (AIT), with loads prescribed according to individual heart rate and lactate profiling obtained during a baseline treadmill test (TRIMPi method), on AS and BRS in patients with early-onset T2D without cardiovascular complications.Twenty-two sedentary overweight T2D patients (aged 57 ± 7 years) were randomized to 12-weeks open-label of supervised AIT by TRIMPi (n = 8) or unsupervised physical activity as per usual care (SOC) (n = 11). Following parameters were evaluated (pre- and post-): anthropometrics; six-minute walking test (6MWT); fasting glucose, insulin, HbA1c; Pulse Wave Velocity (PWV) and Augmentation Index (AIxHR75) using radial approach (SphigmoCor System); BRS using Finapress method.Both interventions significantly improved distance walked during 6MWT (AIT 52 ± 21 m; SOC 39 ± 24 m, p < 0.001 for both). PWV significantly improved with AIT (p < 0.001) whereas did not vary with SOC (p = 0.47). Similar trend was observed for AIxHR75. Resulting percent changes from baseline were significantly better for AIT vs SOC, in both PWV (− 15.8 ± 2.1 vs + 1.50 ± 3.4%, p < 0.001) and AIxHR75 (− 28.9 ± 3.2% vs + 12.7 ± 2.4%, p < 0.001). BRS similarly improved in both groups (p < 0.001 for both), as well as body weight, HbA1c and blood pressure.In sedentary T2D patients, 12-weeks AIT individualized by TRIMPi method improved AS to a greater extent than usual recommendation on physical activity, whilst exerting comparable effects on exercise capacity, glycemic control and body weight. Further researches are needed to ascertain durability of these effects.