Reduced Baroreflex Sensitivity Research Articles

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.

LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 ACTIVITY IS NEGATIVELY ASSOCIATED WITH DECREASED BAROREFLEX SENSITIVITY IN HIGH NORMAL BLOOD PRESSURE

Objective: The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) to hypertension history free control subjects (FHH-) was evaluated. Design and method: A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) and BRSf (Hz/mmHg) were determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). Venous blood was analysed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. Results: A significant negative correlation between spontaneous BRS obtained by both methods and blood pressure (BP) was present (BRS spect r = –0.54, p<0.001, BRS seq r = –0.59, p<0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to group of HNBP without history of hypertension (P= 0.0317 BRS seq, P = 0.0395 BRS spect). There was no difference between both groups of HNBP subjects in BRSf values. Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P = 0.025). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = - 0.6758, P = 0.00028) and BRS obtained by spectral method (r = - 0.5935, P = 0.00031). Conclusions: Lipoprotein associated phospholipase A2 is negatively associated with decreased baroreflex sensitivity in subjects with high normal blood pressure and positive family history of hypertension. These findings demonstrate that reduced baroreflex sensitivity as marker of autonomic dysfunction is linked with vascular inflammation predominantly in otherwise healthy participants with positive history of hypertension that could predispose to increased risk of hypertension. Further research is needed.

What do we know about the role of menopause in cardiovascular autonomic regulation in hypertensive women?

We investigated the systemic arterial hypertension effects on cardiovascular autonomic modulation and baroreflex sensitivity (BRS) in women with or without preserved ovarian function. A total of 120 women were allocated into two groups: middle-aged premenopausal women (42 ± 3 y old; n = 60) and postmenopausal women (57 ± 4 y old; n = 60). Each group was also divided into two smaller groups (n = 30): normotensive and hypertensive. We evaluated hemodynamic and anthropometric parameters, cardiorespiratory fitness, BRS, heart rate variability (HRV), and blood pressure variability. The effects of hypertension and menopause were assessed using a two-way analysis of variance. Post hoc comparisons were performed using the Student-Newman-Keuls test. Comparing premenopausal groups, women with systemic arterial hypertension showed lower BRS (9.1 ± 4.4 vs 13.4 ± 4.2 ms/mm Hg, P < 0.001 ) and HRV total variance (1,451 ± 955 vs 2,483 ± 1,959 ms 2 , P = 0.005) values than normotensive; however, the vagal predominance still remained. On the other hand, both postmenopausal groups showed an expressive reduction in BRS (8.3 ± 4.2 vs 11.3 ± 4.8 ms/mm Hg, P < 0.001) and HRV characterized by sympathetic modulation predominance (low-frequency oscillations; 56% ± 17 vs 44% ± 17, P < 0.001), in addition to a significant increase in blood pressure variability variance (28.4 ± 14.9 vs 22.4 ± 12.5 mm Hg 2 , P = 0.015) compared with premenopausal groups. Comparing both postmenopausal groups, the hypertensive group had significantly lower values ​​of HRV total variance (635 ± 449 vs 2,053 ± 1,720 ms 2 , P < 0.001) and BRS (5.3 ± 2.8 vs 11.3 ± 3.2 ms/mm Hg) than the normotensive. Hypertensive middle-aged premenopausal women present HRV autonomic modulation impairment, but they still maintain a vagal predominance. After menopause, even normotensive women show sympathetic autonomic predominance, which may also be associated with aging. Furthermore, postmenopausal women with hypertension present even worse cardiac autonomic modulation.

The association of race, sex, and neighborhood disadvantage with baroreflex sensitivity in the U.S. POINTER Neurovascular ancillary study

AbstractBackgroundThe arterial baroreflex maintains stable blood flow to the brain. Reduced baroreflex sensitivity for modulation of heart rate (BRS) has been observed in patients with Alzheimer’s disease (AD) and mild cognitive impairment and may be impacted by race, ethnicity, sex, and socioeconomic factors such as the Area Deprivation Index (ADI), a validated, neighborhood‐level composite index that incorporates 17 social determinants of health. However, these relationships have not been well described.MethodThis study utilized baseline data from 196 participants enrolled in the U.S. POINTER Neurovascular study, an ancillary to the parent U.S. POINTER multi‐site lifestyle intervention trial that adds assessments of autonomic function and vascular structure and function. BRS was calculated from continuous blood pressure and electrocardiogram recording using the slope of the regression line between changes in systolic blood pressure and RR interval values in the same direction, with higher BRS indicating better autonomic function. ADI scores ranging from 1 to 10 were calculated using 9‐digit zip codes, with 10 indicating the greatest disadvantage. Analysis of variance and linear regression were used to evaluate associations between measures of interest.ResultThe average age of the study population was 67.9 ± 5.4 years, 64 (17%) were males, and 60 (30.6%) identified as people of color (POC). Overall, the mean BRS was 9.2 ± 4.6 ms/mmHg, and the average ADI score was 4.56 ± 2.69 (range: 1 to 10), corresponding to a national ADI percentile of 40.7 ± 26.1 (range: 3 to 100). Less than a quarter of participants (n = 42, 21.4%) had an ADI percentile &gt;67, indicating a moderate to high level of neighborhood disadvantage. White participants had lower BRS compared to POC (8.60 ± 4.49 vs. 10.60 ± 4.61 ms/mmHg, p = 0.0048). In a multiple regression model adjusting for demographics and ADI, sex (p = 0.0283), race and ethnicity (p = 0.0049), and education (p = 0.0196) were significantly associated with BRS, indicating better autonomic function in men, POC, and those with higher education. ADI was not associated with BRS.ConclusionRace, ethnicity, and education impact autonomic function. Further investigations are needed to assess the impact of other demographic and socioeconomic factors on neurovascular health.

Association of rs2073618 polymorphism and osteoprotegerin levels with hypertension and cardiovascular risks in patients with type 2 diabetes mellitus

There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (β − 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism.

Trained hypertensive rats exhibit decreased transcellular vesicle trafficking, increased tight junctions' density, restored blood-brain barrier permeability and normalized autonomic control of the circulation.

Introduction: Chronic hypertension is accompanied by either blood-brain barrier (BBB) leakage and autonomic dysfunction. There is no consensus on the mechanism determining increased BBB permeability within autonomic areas. While some reports suggested tight junction's breakdown, others indicated the involvement of transcytosis rather than paracellular transport changes. Interestingly, exercise training was able to restore both BBB permeability and autonomic control of the circulation. We sought now to clarify the mechanism(s) governing hypertension- and exercise-induced BBB permeability. Methods: Spontaneously hypertensive rats (SHR) and normotensive controls submitted to 4-week aerobic training (T) or sedentary protocol (S) were chronically cannulated for baseline hemodynamic and autonomic recordings and evaluation of BBB permeability. Brains were harvested for measurement of BBB function (FITC-10kDa leakage), ultrastructural analysis of BBB constituents (transmission electron microscopy) and caveolin-1 expression (immunofluorescence). Results: In SHR-S the increased pressure, augmented sympathetic vasomotor activity, higher sympathetic and lower parasympathetic modulation of the heart and the reduced baroreflex sensitivity were accompanied by robust FITC-10kDa leakage, large increase in transcytotic vesicles number/capillary, but no change in tight junctions' density within the paraventricular nucleus of the hypothalamus, the nucleus of the solitary tract and the rostral ventrolateral medulla. SHR-T exhibited restored BBB permeability and normalized vesicles counting/capillary simultaneously with a normal autonomic modulation of heart and vessels, resting bradycardia and partial pressure reduction. Caveolin-1 expression ratified the counting of transcellular, not other cytoplasmatic vesicles. Additionally, T caused in both groups significant increases in tight junctions' extension/capillary border. Discussion: Data indicate that transcytosis, not the paracellular transport, is the primary mechanism underlying both hypertension- and exercise-induced BBB permeability changes within autonomic areas. The reduced BBB permeability contributes to normalize the autonomic control of the circulation, which suppresses pressure variability and reduces the occurrence of end-organ damage in the trained SHR. Data also disclose that hypertension does not change but exercise training strengthens the resistance of the paracellular pathway in both strains.

Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis.

Cardiovascular autonomic neuropathy (CAN) is a severe complication of the advance stage of diabetes. More than 50% of diabetic patients diagnosed with peripheral neuropathy will have CAN, with clinical manifestations including tachycardia, severe orthostatic hypotension, syncope, and physical exercise intolerance. Since the prevalence of diabetes is increasing, a concomitant increase in CAN is expected and will reduce quality of life and increase mortality. Autonomic dysfunction is associated with reduced baroreflex sensitivity and impairment of sympathetic and parasympathetic modulation. Various autonomic function tests are used to diagnose CAN, a condition without adequate treatment. It is important to consider the control of glucose level and blood pressure as key factors for preventing CAN progression. However, altered biomarkers of inflammatory and endothelial function, increased purinergic receptor expression, and exacerbated oxidative stress lead to possible targets for the treatment of CAN. The present review describes the molecular alterations seen in CAN, diagnosis, and possible alternative treatments.

Hypertension attenuates the link of osteoprotegerin to reduced baroreflex sensitivity in type 2 diabetes mellitus patients on oral antidiabetic and antihypertensive therapy – a cross sectional study

PurposeDecreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2 diabetes (T2D) patients receiving oral antidiabetic drugs (OAD) with and without hypertension has been assessed.Materials and methodsNinety-two T2D patients on OAD without hypertension (control group) and eighty-eight diabetic patients with hypertension on OAD and antihypertensive drugs (test group) matched for age, gender, body mass index, serum glucose, glycated haemoglobin, and duration of the disease were recruited for the study. Their blood pressure (BP) variability including BRS, heart rate variability (HRV), insulin, lipid profile, osteoprotegerin (OPG), and tumor necrosis factor-α (TNF-α) were estimated. The association of various factors with BRS was assessed by Spearman correlation and multiple regression analysis.ResultsBRS was decreased (13.90 ± 5.27 vs 6.76 ± 4.58), HRV sympathetic indices [LFnu, LF-HF ratio (1.30 ± 0.49 vs 1.93 ± 0.62)], HOMA-IR, atherogenic index of plasma (AIP), OPG (223.08 ± 103.86 vs 287.60 ± 121.36) and TNF-α were increased, and parasympathetic indices [TP (1012.90 ± 316.18 vs 625.88 ± 229.84), RMSSD, SDNN, NN50, pNN50] were decreased in the test group compared to control group. In control group, parasympathetic indices, AIP, OPG, and TNF-α had a significant correlation and OPG had an independent association (β − 0.344; p 0.004) with BRS. In test group, BP, LF-HF ratio, parasympathetic indices, AIP, OPG, and TNF-α had significant correlation, and TNF-α alone (β − 0.297; p 0.022) had an independent contribution to decreased BRS.ConclusionDespite antidiabetic and antihypertensive treatments, T2D patients with hypertension had more cardiometabolic risks in comparison to normotensive T2D patients. Inflammation could be the inciting factor for rise in BP and decrease in BRS (CV risk) in hypertensive T2D patients. Hypertension in diabetes could attenuate the link of OPG to the reduction in BRS. Reduction in BRS could be a physiological marker of CV risk in T2D patients treated with OAD.

Thermal acclimation and acute temperature effects on cardiac barostatic reflexes in rainbow trout (Oncorhynchus mykiss)

Acute warming raises the metabolism of fish, which is matched by increased heart rate. However, thermal acclimation may reduce heart rate through combinations of lowered intrinsic pacemaker rate and increased inhibitory vagal tone. This could affect the baroreflex, which regulates arterial blood pressure through heart rate changes via altered vagal tone. Using pharmacological tools, we assessed autonomic tones and baroreflex regulation of heart rate in rainbow trout (Oncorhynchus mykiss) at 11 °C, and after acute (24 h, 17°Cacute) or chronic (>7 weeks, 17°Cchronic) warming to 17 °C. We hypothesised that warm acclimation would manifest as reduced heart rate and elevated vagal tone in 17°Cchronic trout relative to 11 °C and 17°Cacute trout, which would increase baroreflex gain and the scope for fH increase through vagal release during hypotension. Compared to 11 °C, the 17°Cacute group exhibited slightly higher heart rate (Q10 = 1.5) and a strong trend for elevated vagal tone (54%). Surprisingly, however, routine heart rate was unaltered by warm acclimation (Q10 = 1.6), while intrinsic heart rate and vagal tone (22%) declined. Consequently, baroreflex sensitivity to reduced blood pressure was elevated in the 17°Cacute group but returned towards 11 °C conditions in the 17°Cchronic group. Atropine abolished nearly all chronotropic changes. Bradycardic responses to hypertension and cardiac adrenergic tone were unaltered across temperature treatments. The lack of a clear acclimation effect on routine heart rate in the present study is likely explained by a seasonal effect as the experiments were performed in early winter. Nonetheless, we conclude that baroreflex sensitivity in trout is thermally plastic; the heightened baroreflex sensitivity to hypotension following acute warming likely serves to safeguard tissue oxygen delivery as metabolism is elevated, while the reduced baroreflex sensitivity observed with warm acclimation may be linked to a pronounced metabolic down-regulation.

Baroreflex sensitivity during rest and pressor challenges in obstructive sleep apnea patients with and without CPAP

IntroductionObstructive sleep apnea (OSA) increases sympathetic vasoconstrictor drive and reduces baroreflex sensitivity (BRS), the degree to which blood pressure changes modify cardiac output. Whether nighttime continuous positive airway pressure (CPAP) corrects BRS in the awake state in OSA remains unclear. We assessed spontaneous BRS using non-invasive continuous BP and ECG recordings at rest and during handgrip and Valsalva challenges, maneuvers that increase vasoconstrictor drive with progressively higher BP, in untreated OSA (unOSA), CPAP-treated OSA (cpOSA) and healthy (CON) participants. MethodsIn a cross-sectional study of 104 participants, 34 unOSA (age mean±std, 50.6±14.1years; Respiratory Event Index [REI] 21.0±15.3 events/hour; 22male), 31 cpOSA (49.6±14.5years; REI 23.0±14.2 events/hour; 22male; self-report 4+hours/night,5+days/week,6months), and 39 CON (42.2±15.0years; 17male), we calculated BRS at rest and during handgrip and Valsalva. Additionally, we correlated BP variability (BPV) with BRS during these protocols. ResultsBRS in unOSA, cpOSA and CON was, respectively (mean±sdv in ms/mmHg), at rest: 14.8±11.8, 15.8±17.0, 16.1±11.3; during handgrip 13.3±7.6, 12.7±8.4, 16.4±8.7; and during Valsalva 12.7±8.0, 11.5±6.6, 15.1±8.9. BRS was lower in cpOSA than CON for handgrip (p=0.04) and Valsalva (p=0.03). BRS was negatively correlated with BPV in unOSA during Valsalva and handgrip for cpOSA, both R=−0.4 (p=0.02). BRS was negatively correlated with OSA severity (levels: none, mild, moderate, severe) at R=−0.2 (p=0.04,n=104). ConclusionsAs expected, BRS was lower and BPV higher in OSA during the pressor challenges, and disease severity negatively correlated with BRS. In this cross-sectional study, both CPAP-treated (self-reported) and untreated OSA showed reduced BRS, leaving open whether within-person CPAP improves BRS.

Anti‐depressant lithium compounds reliefs cardiorespiratory disturbances and improves cardiac function in experimental non‐ischemic heart failure

Non‐ischemic heart failure (HF) is a complex medical problem with a high incidence among the older population. While several efforts have been made to improve HF outcomes there is an urgent need for new strategies to reduce mortality rates. Sympathoexcitation and disordered breathing are both considered hallmarks of HF and are closely related to disease progression. Lithium salts has been largely used as anti‐depressants; however, lithium compounds also showed several pleiotropic effects some of them linked to the origin of cardiorespiratory disorders in HF (i.e. oxidative stress). Accordingly, using drug repurposing strategy we aimed to define whether lithium treatment improve cardiorespiratory function in experimental HF. Male Sprague‐Dawley rats underwent volume overload to induce non‐ischemic HF. Four weeks after HF induction, an osmotic minipump containing lithium chloride (Li+, 2 meq/Kg/day) was subcutaneously implanted for drug delivery. Cardiac autonomic and baroreflex function, ventilatory chemoreflex drive and disordered breathing were evaluated after 4 weeks of Li+ treatment in freely moving rats. In addition, cardiac function was determine using PV‐loops. Compared to Sham rats, HF animals displayed autonomic imbalance, reduced baroreflex sensitivity, higher incidence of cardiac arrhythmias, enhanced central chemoreflex and breathing disorders. Cardiac diastolic dysfunction was evident in HF animals compared to Sham animals. HF rats that underwent Li+ treatment showed significant (p&lt;0.05) improvements in cardiac autonomic function as evidenced by reduced low‐to‐high frequency ratio of heart rate variability (LF/HF: 2.8 ± 0.3 vs. 0.9 ± 0.4; HF+Veh vs. HF+Li+), baroreflex sensitivity (BRS: 2.0 ± 0.5 vs. 5.8 ± 1.0 ms/mmHg; HF+Veh vs. HF+Li+) and reduced cardiac arrhythmogenesis (PVC: 220 ± 50 vs. 30 ± 10 events/h; HF+Veh vs. HF+Li+). Furthermore, Li+ treatment in HF completely normalized central chemoreflex drive. Indeed, hypercapnic ventilatory responses obtained in HF+Li+ rats were undistinguishable from the ones obtained in Sham rats (HCVR: 1.7 ± 0.4 vs. 2.0 ± 0.4 DVe/FiCO2; HF+Veh vs. HF+Li+). Also, breathing disorders (i.e. apneas/hypopneas) were markedly reduced by Li+ treatment in HF (AHI: 8.5 ± 1.0 vs. 3.7 ± 0.8; HF+Veh vs. HF+Li+). Lastly, HF+Li+ treated rats displayed marked improvements in cardiac diastolic function (~2.5‐fold reduction in EDPVR) compared to HF+Veh treated rats. We found that the beneficial effects of Li+were partially associated with upregulation of the Nrf2 pathway and related antioxidant genes (i.e. SOD2), reductions in tissue oxidative stress and decreases in the expression of pro‐inflammatory cytokines (i.e. TNF‐a) in HF rats. Our results support the notion that lithium compounds may offer new avenues for the treatment of cardiorespiratory disorders and cardiac diastolic dysfunction in non‐ischemic HF.

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

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

Dynamics of the baroreflex sensitivity during combined anesthesia with sevoflurane or propofol: a randomized trial

INTRODUCTION: A significant number of complications is still a serious problem in abdominal surgery. It is known that patients with low baroreflex sensitivity are more prone to hemodynamic instability during general anesthesia, which allows them to be identified as a risk group. OBJECTIVE: To evaluate the dynamics of baroreflex sensitivity (BRS) during major abdominal surgery in patients with different risk of critical incidents under combined anesthesia with propofol or sevoflurane. MATERIALS AND METHODS: A randomized study was conducted in 160 patients (80 high-risk and 80 low-risk patients), who were randomized into subgroups according to the type of anesthesia (propofol or sevoflurane) to assess the effect of the type of anesthesia critical incidents and baroreflex dynamics. RESULTS: After the induction there was a trend towards a decrease in BRS, while in subgroups with initially low values of BRS, it decreased below 3 ms/mmHg. After the end of operation and 6 hours after extubation, there were no significant changes in comparison with intraoperative values. Evaluation of BRS after 24 hours showed that BRS in all subgroups was significantly higher than at previous time points, but did not return to baseline values. At 6 hours postoperatively, in low-risk patients, BRS values were below 3 ms/mmHg in 12.5 % with propofol, and in 10 % with sevoflurane, in high-risk patients — in 45 % and 42.5 % of cases, respectively. At 24 hours, in the low-risk group, only two patients in the propofol anesthesia group and one in the sevoflurane anesthesia subgroup experienced this dysfunction. CONCLUSIONS: Both anesthesia with propofol and anesthesia with sevoflurane lead to a decrease in the sensitivity of the arterial baroreflex, which is not fully restored 24 hours after the end of the operation. High-risk patients with initially reduced baroreflex sensitivity show more frequent postoperative baroreflex dysfunction.

346 Baroreflex sensitivity and autonomic function in Takotsubo syndrome long after the acute phase

Abstract Aims Takotsubo Syndrome (TS) occurs as an acute coronary syndrome (ACS) characterized by severe left ventricular (LV) dysfunction that typically recovers spontaneously within days or weeks and in the absence of obstructive coronary artery disease. Although during the acute phase it is well documented that an exaggerated sympathetic tone plays a central role in the development of TS, whether an impaired sympatho-vagal balance may persist long after the acute phase, despite the recovery of left ventricular function, is still an open issue. Interestingly, recent evidences suggest that an impairment in central autonomic network not only persist long after the acute event but also may be pre-existent before the acute onset of TS. The Aim of the study was to investigate whether an impairment of the autonomic function is still present long after a TS event. Methods and results We evaluated 67 patients (91% female, mean age 66 ± 8 years) divided into three groups: 24 with a history of TS (1 year after acute event), 21 subjects with a previous history of acute coronary syndrome (ACS) and complete LV ejection fraction recovery (1 year after acute event) and 22 age- and gender-matched healthy subjects. All patients underwent a non-invasive beat-to-beat arterial blood pressure and heart rate recording (short term: 5 min), after at least 3 days of β-blockers wash-out, to obtain heart rate variability (HRV) and spontaneous baroreflex sensitivity (sBRS) data. An overall autonomic dysfunction was found in both TS and ACS groups compared to controls. In particular, a lower heart rate variability, expressed as lower SDNN, has been found in TS and ACS groups compared to controls (31 ± 12 vs. 25 ± 11 vs. 41 ± 22; P = 0.006—Figure A) as a consequence of blunted vagal tone, expressed as lower RMSSD (20 ± 12 vs. 19 ± 11 vs. 40 ± 37; P = 0.007—Figure B) and higher sympathetic tone, expressed as higher LF/HF ratio (P = 0.007 Figure C) which was found to be higher in TS even when compared to ACS (TS: 3.5 ± 2.5 vs. ACS: 2.1 ± 1.7; P = 0.011). Moreover, fractal analysis of HRV showed higher complexity of heart rate regulation, expressed as higher fractal dimension (DFA 1.48 ± 0.06 vs. 1.53 ± 0.05 vs. 1.40 ± 0.10; P &amp;lt; 0.0001—Figure D), in both TS and ACS compared to controls. Interestingly, spontaneous BRS showed the lowest values in the TS group (sSBP: 5.6 ± 2.6 vs. 7.5 ± 3.0 vs. 12.1 ± 11.9; P = 0.027—Figure E), associated with highest levels of sympathetic peripheral control of systolic blood pressure (SBP), expressed as LF-BRS (13.7 ± 9.6 vs. 8.3 ± 5.2 ± 6.8 ± 5.8; P = 0.008—Figure F). Conclusions An autonomic dysfunction, characterized by a hyper-sympathetic tone, reduced baroreflex sensitivity and increased peripheral adrenergic control of blood pressure, persists in TS patients long after the acute phase.

Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia

Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator’s signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-α (TNF-α, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-α, interleukin-1β (IL-1β), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-α mediated central effect was evaluated in TNF-α-infused pregnant rats. TNF-α infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-α-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE.

Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors.

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

Abstract MP55: Bardet-biedl Syndrome 3 Gene In Pomc Neurons Regulates Glucose Homeostasis And Baroreflex Sensitivity

Bardet-Biedl syndrome (BBS) proteins have emerged as critical regulators of various physiological functions including energy and glucose homeostasis, autonomic function and blood pressure. BBS3 protein is a cilia related protein that mediates the ciliary localization of the BBSome, a protein complex composed of eight BBS protein. Consistent with this, we found that BBS3 gene knockout in human RPE1 cells disrupt the ciliary localization of BBS2 and BBS9 proteins, indicating a loss of BBSome-mediated cargo trafficking to cilia. We previously demonstrated that disruption of the BBSome through Bbs1 gene deletion in the anorexigenic pro-opiomelanocortin (POMC) neurons altered energy homeostasis and sympathetic nerve traffic. However, the significance of BBS3-mediated ciliary localization of the BBSome in POMC neurons is not clear. To address this, we investigated the consequence of Bbs3 gene deletion in POMC neurons . We generated mice lacking the Bbs3 gene in POMC neurons by crossing Bbs3 fl/fl mice with mice expressing inducible Cre in POMC neurons (POMC ERCre ). To visualize Cre recombinase we further crossed POMC ERCre /Bbs3 fl/fl mice with tdTomato reporter mice. To induce Cre expression tamoxifen (75 mg/kg for 5 days) was injected at 6 weeks of age. Interestingly, both male and female POMC ERCre /Bbs3 fl/fl mice did not develop obesity as indicated by the lack of difference in body weight (male 28.1 + 0.5 vs 28.3 + 1.2g, female 21.9 + 0.7 vs 21.4 + 0.5g), fat mass (male 2.9 + .0.4 vs 3.4 + 0.5g, female 2.7 + .3 vs 2.3 + 0.2g) and weight of white and brown fat pads. Insulin and glucose tolerance tests revealed that POMC ERCre /Bbs3 fl/fl mice have glucose intolerance, whereas insulin sensitivity was normal. Blood pressure and renal SNA were comparable between POMC ERCre /Bbs3 fl/fl and control mice measured in the conscious state. In contrast, measurement of renal SNA response to changes in arterial pressure evoked by infusion of sodium nitroprusside and phenylephrine showed reduced baroreflex sensitivity in POMC ERCre /Bbs3 fl/fl mice. These findings demonstrate that POMC neuron BBS3, that mediate cargo transport to cilia, is not necessary for the regulation of energy homeostasis, but is involved in the regulation of glucose homeostasis and baroreflex sensitivity.

Early Left Ventricular Diastolic Dysfunction, Reduced Baroreflex Sensitivity, and Cardiac Autonomic Imbalance in Anabolic-Androgenic Steroid Users.

The effects of androgen anabolic steroids (AAS) use on athletes’ cardiac autonomic activity in terms of baroreflex sensitivity (BRS), and heart rate variability (HRV) have not yet been adequately studied. Furthermore, there is no information to describe the possible relationship between the structural and functional cardiac remodeling and the cardiac autonomic nervous system changes caused by AAS abuse. Thus, we aimed to study the effects of long-term AAS abuse on cardiac autonomic efficacy and cardiac adaptations in strength-trained athletes. In total, 80 strength-trained athletes (weightlifters and bodybuilders) participated in the study. Notably, 40 of them using AAS according to their state formed group A, 40 nonuser strength-trained athletes comprised group B, and 40 healthy nonathletes (group C) were used as controls. All subjects underwent a head-up tilt test using the 30 min protocol to evaluate the baroreflex sensitivity and short HRV modulation. Furthermore, all athletes undertook standard echocardiography, a cardiac tissue Doppler imaging (TDI) study, and a maximal spiroergometric test on a treadmill to estimate their maximum oxygen consumption (VO2max). The tilt test results showed that group A presented a significantly lower BRS and baroreflex effectiveness index than group B by 13.8% and 10.7%, respectively (p < 0.05). Regarding short-term HRV analysis, a significant increase was observed in sympathetic activity in AAS users. Moreover, athletes of group A showed increased left ventricular (LV) mass index (LVMI) by 8.9% (p < 0.05), compared to group B. However, no difference was found in LV ejection fraction between the groups. TDI measurements indicated that AAS users had decreased septal and lateral peak E’ by 38.0% (p < 0.05) and 32.1% (p < 0.05), respectively, and increased E/E’ by 32.0% (p < 0.05), compared to group B. This LV diastolic function alteration was correlated with the year of AAS abuse. A significant correlation was established between BRS depression and LV diastolic impairment in AAS users. Cardiopulmonary test results showed that AAS users had significantly higher time to exhaustion by 11.0 % (p < 0.05) and VO2max by 15.1% (p < 0.05), compared to controls. A significant correlation was found between VO2max and LVMI in AAS users. The results of the present study indicated that long-term AAS use in strength-trained athletes led to altered cardiovascular autonomic modulations, which were associated with indices of early LV diastolic dysfunction.

Negative association between lipoprotein associated phospholipase A2 activity and baroreflex sensitivity in subjects with high normal blood pressure and a positive family history of hypertension.

The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) and hypertension history free control subjects (FHH-) was evaluated. A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) was determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and RR interval, controlled breathing at a frequency of 0.33 Hz). Venous blood was analyzed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. A significant negative correlation between spontaneous BRS obtained by both methods and systolic blood pressure (BP) was present (BRS spect r = -0.54, P<0.001, BRS seq r = -0.59, P<0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to the group of HNBP FHH- (P = 0.0317 BRS seq, P = 0.0395 BRS spect). Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P<0.05). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = -0.798, R2 = 0.636, P<0.001) in the HNBP FHH+ subjects. These findings demonstrate that reduced baroreflex sensitivity, as a marker of autonomic dysfunction, is associated with vascular inflammation, predominantly in otherwise healthy participants with a positive family history of hypertension who could predispose to increased risk of hypertension. We conclude that our transversal study suggests that a lowbaroreflex sensitivity could be an early sign of autonomic dysfunction even in the prehypertensive period, and to corroborate these findings, a longitudinal study is needed.

The Link Between Autonomic Nervous System and Rheumatoid Arthritis: From Bench to Bedside.

Neuronal stimulation is an emerging field of research focused on the management and treatment of various diseases through the reestablishment of physiological homeostasis. Electrical vagus nerve stimulation has recently been proposed as a revolutionary therapeutic option for rheumatoid arthritis (RA) in combination with or even as a replacement for conventional and biological drugs. In the past few years, disruption of the autonomic system has been linked to RA onset and activity. Novel research on the link between the autonomic nervous system and the immune system (immune-autonomics) has paved the way for the development of innovative RA management strategies. Clinical evidence supports this approach. Cardiovascular involvement, in terms of reduced baroreflex sensitivity and heart rate variability-derived indices, and mood disorders, common comorbidities in patients with RA, have been linked to autonomic nervous system dysfunction, which in turn is influenced by increased levels of circulating pro-inflammatory cytokines. This narrative review provides an overview of the autonomic nervous system and RA connection, discussing most of the common cardiac and mental health-related RA comorbidities and their potential relationships to systemic and joint inflammation.