Spontaneous Baroreflex Research Articles

Inspiratory muscle training improves breathing pattern and sympatho-vagal balance but not spontaneous baroreflex sensitivity in older women

Even though recent studies reported a positive inspiratory muscle training (IMT) effect on cardiovascular autonomic modulation, its underlying mechanisms as the breathing pattern remain unclear. The study aimed to investigate the IMT effects on resting heart rate variability (HRV), spontaneous baroreflex sensitivity (BRS), and spontaneous breathing pattern in older women. Fourteen healthy older women participated in this study, allocated in IMT (50 % MIP; n = 8) or Sham (5% MIP; n = 6) protocols for four weeks. Blood pressure, heart rate, and ventilatory data were continuously recorded before and after interventions. After four weeks, IMT-group increased maximal inspiratory pressure and vagal-mediated HRV, following by the reduction of sympatho-mediated HRV and the inspiratory time during the spontaneous breathing cycle compared to Sham-group, but did not change BRS. Therefore, the shorter inspiratory time suggests a putative mechanism behind improved vagal-mediated HRV post-IMT in older women.

LONG-TERM EFFECT OF ANTIHYPERTENSIVE AGENTS ON THE NEURAL BAROREFLEX SENSITIVITY-A SUBSTUDY OF THE PARIS PROSPECTIVE STUDY III

Objective: The baroreflex is a crucial mechanism regulating moment-to-moment blood pressure (BP) to ensure appropriate flow and pressure to the brain and other organs. All antihypertensive treatments, because of their BP lowering effect, interact with the autonomic nervous system by stimulating the sympathetic response. In addition, specific drugs may further interact with the BRS because of their specific mode of action. Whether antihypertensive agents have remnant effect is still unknown. Design and method: In the Paris Prospective Study III, spontaneous baroreflex, carotid stiffness and pharmacological drugs intake were available in 7967 adults (mean age of 60 ± 6 years, 62% men). The neural component of the baroreflex sensitivity (nBRS) was obtained with a cross-spectral analysis of variations in carotid distention rate and R-R intervals. Individuals with a BP lowering medication (BP-treated) were paired to non-BP treated individuals (controls) with similar cardiovascular comorbidities using a propensity score matching procedure (n = 1182 pairs). Results: Sympathetic activity was higher in the BP-treated group compared to their matched-controls, as shown by the increased spectral power of distention rate in the low frequency band (log LF distrate: 4.106 ± 0.530 vs 4.055 ± 0.514, p = 0.018). Amongst pharmacological classes of BP lowering agents, only agents acting on the angiotensin system (ACEi-ARB) were associated with nBRS. Compared to their matched controls (n = 331 pairs), ACEi-ARB users had lower nBRS (2.79 ± 0.66 (ln) vs. 2.90 ± 0.62 (ln), p = 0.03). After adjustment for carotid stiffness (stdbeta = 0.25, p < 0.001) and systolic pressure (stdbeta = -0.20, p < 0.001), ACEi-ARB remained significantly associated with nBRS (stdbeta = -0.09, p = 0.025). Conclusions: In this community-based population study, antihypertensive treatments induced activation of the autonomic nervous system independently of cardiovascular comorbidities. Taken as a whole, BP treatments did not have any effect on the neural component of the baroreflex loop, with the exception of ACEi-ARB which were negatively associated with nBRS. This effect was independent of BP and stiffness, which may suggest an inhibition of sympathetic activity by ACEi-ARB.

Cardiovascular and Autonomic Responses after a Single Bout of Resistance Exercise in Men with Untreated Stage 2 Hypertension.

The aim of this paper is to assess the integrated responses of ambulatory blood pressure (BP), cardiac autonomic modulation, spontaneous baroreflex sensitivity (BRS), and vascular reactivity after a single bout of resistance exercise (RE) in men with stage 2 hypertension who have never been treated before. Ten hypertensive men were subjected to a RE session of three sets of 20 repetitions and an intensity of 40% of the 1-repetition maximum (RM) test in seven different exercises. For the control (CTR) session, the volunteers were positioned on the exercise machines but did not perform any exercise. Forearm blood flow was measured by venous occlusion plethysmography. We also analyzed the heart rate variability (HRV), ambulatory BP, blood pressure variability (BPV), and BRS. All measurements were performed at different timepoints: baseline, 20 min, 80 min, and 24 h after both RE and CTR sessions. There were no differences in ambulatory BP over the 24 h between the RE and CTR sessions. However, the area under the curve of diastolic BP decreased after the RE session. Heart rate (HR) and cardiac output increased for up to 80 and 20 min after RE, respectively. Similarly, forearm blood flow, conductance, and vascular reactivity increased 20 min after RE (p < 0.05). In contrast, HRV and BRS decreased immediately after exercise and remained lower for 20 min after RE. We conclude that a single bout of RE induced an increase in vascular reactivity and reduced the pressure load by attenuating AUC of DBP in hypertensive individuals who had never been treated with antihypertensive medications.

SAR340835, a Novel Selective Na+/Ca2+ Exchanger Inhibitor, Improves Cardiac Function and Restores Sympathovagal Balance in Heart Failure.

In failing hearts, Na+/Ca2+ exchanger (NCX) overactivity contributes to Ca2+ depletion, leading to contractile dysfunction. Inhibition of NCX is expected to normalize Ca2+ mishandling, to limit afterdepolarization-related arrhythmias, and to improve cardiac function in heart failure (HF). SAR340835/SAR296968 is a selective NCX inhibitor for all NCX isoforms across species, including human, with no effect on the native voltage-dependent calcium and sodium currents in vitro. Additionally, it showed in vitro and in vivo antiarrhythmic properties in several models of early and delayed afterdepolarization-related arrhythmias. Its effect on cardiac function was studied under intravenous infusion at 250,750 or 1500 µg/kg per hour in dogs, which were either normal or submitted to chronic ventricular pacing at 240 bpm (HF dogs). HF dogs were infused with the reference inotrope dobutamine (10 µg/kg per minute, i.v.). In normal dogs, NCX inhibitor increased cardiac contractility (dP/dtmax) and stroke volume (SV) and tended to reduce heart rate (HR). In HF dogs, NCX inhibitor significantly and dose-dependently increased SV from the first dose (+28.5%, +48.8%, and +62% at 250, 750, and 1500 µg/kg per hour, respectively) while significantly increasing dP/dtmax only at 1500 (+33%). Furthermore, NCX inhibitor significantly restored sympathovagal balance and spontaneous baroreflex sensitivity (BRS) from the first dose and reduced HR at the highest dose. In HF dogs, dobutamine significantly increased dP/dtmax and SV (+68.8%) but did not change HR, sympathovagal balance, or BRS. Overall, SAR340835, a selective potent NCX inhibitor, displayed a unique therapeutic profile, combining antiarrhythmic properties, capacity to restore systolic function, sympathovagal balance, and BRS in HF dogs. NCX inhibitors may offer new therapeutic options for acute HF treatment. SIGNIFICANCE STATEMENT: HF is facing growing health and economic burden. Moreover, patients hospitalized for acute heart failure are at high risk of decompensation recurrence, and no current acute decompensated HF therapy definitively improved outcomes. A new potent, Na+/Ca2+ exchanger inhibitor SAR340835 with antiarrhythmic properties improved systolic function of failing hearts without creating hypotension, while reducing heart rate and restoring sympathovagal balance. SAR340835 may offer a unique and attractive pharmacological profile for patients with acute heart failure as compared with current inotrope, such as dobutamine.

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice.

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. The baroreflex is a key homeostatic mechanism to counteract acute, short-term changes in arterial BP and to maintain BP in a relatively narrow physiological range. BP is sensed by baroreceptors located in the aortic arch and carotid sinus. When BP changes, signals are transmitted to the central nervous system and are then communicated to the parasympathetic and sympathetic branches of the autonomic nervous system to adjust HR. A rise in BP causes a reflex decrease in HR, a drop in BP causes a reflex increase in HR. Baroreflex sensitivity (BRS) is the quantitative relationship between changes in arterial BP and corresponding changes in HR. Cardiovascular diseases are often associated with impaired baroreflex function. In various studies reduced BRS has been reported in e.g., heart failure, myocardial infarction, or coronary artery disease. Determination of BRS requires information from both BP and HR, which can be recorded simultaneously using telemetric devices. The surgical procedure is described beginning with the insertion of the pressure sensor into the left carotid artery and positioning of its tip in the aortic arch to monitor arterial pressure followed by the subcutaneous placement of the transmitter and ECG electrodes. We also describe postoperative intensive care and analgesic management. After a two-week period of post-surgery recovery long-term ECG and BP recordings are performed in conscious and unrestrained mice. Finally, we include examples of high-quality recordings and the analysis of spontaneous baroreceptor sensitivity using the sequence method.

Supine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia Syndrome

Upright postural tachycardia syndrome (POTS) resembles hemorrhage with reduced central blood volume, parasympathetic withdrawal, and sympathetic activation. Baroreflex dysfunction causes low heart rate variability, enhanced blood pressure variability, and decreased maximum baroreflex gain (Gmax) putatively measured by spontaneous fluctuation of blood pressure and heart rate. We investigated whether/how cardiovagal baroreflex in POTS differ from control, supine, and upright by comparing indices of spontaneous baroreflex function to that measured using the reference standard modified Oxford method. This uses sodium nitroprusside and phenylephrine to generate the sigmoidal cardiovagal baroreflex curve. Baroreflex in POTS was evaluated supine and upright untreated and then treated to determine whether pyridostigmine or digoxin (a vagotonic agent) corrects baroreflex deficits. Supine, Gmax was reduced by 25% in POTS compared with controls, and descriptors of this sigmoidal relationship showed a reduction, downward shift, and left shift of the response to the pharmacological decrease and increase in blood pressure. Digoxin normalized supine cardiovagal baroreflex while pyridostigmine resulted in partial normalization as Gmax, and other descriptors of these relationships were similar to control. Upright, cardiovagal curves were distorted and displaced in untreated POTS, while digoxin and pyridostigmine left shifted the cardiovagal curves due to sympathetic activity. Cardiovagal baroreflex deficits in POTS relate to parasympathetic withdrawal while supine, remediated completely by digoxin, and sympathetic activation upright through alteration of baroreflex responsivity. Since these baroreflex effects resemble those measured following microgravity/chronic bedrest, vagotonic/sympatholytic treatment combined with aerobic exercise might normalize the cardiovagal baroreflex and provide therapeutic benefit in patients with POTS.

Hemodynamics and cardiac autonomic modulation after an acute concurrent exercise circuit in older individuals with pre- to established hypertension

OBJECTIVES:Few studies have investigated whether post-exercise hypotension (PEH) after concurrent exercise (CEX) is related to changes in cardiac output (Q) and systemic vascular resistance (SVR) in older individuals. We tested whether PEH after a single bout of CEX circuits performed in open-access facilities at the Third Age Academies (TAA) in Rio de Janeiro City (Brazil) would be concomitant with decreased Q and SVR in individuals aged ≥60 years with prehypertension. Moreover, we assessed autonomic modulation as a potential mechanism underlying PEH.METHODS:Fourteen individuals (age, 65.8±0.9 y; systolic/diastolic blood pressure [SBP/DBP], 132.4±12.1/72.8±10.8 mmHg; with half of the patients taking antihypertensive medications) had their blood pressure (BP), heart rate (HR), Q, SVR, HR variability (HRV), and spontaneous baroreflex sensitivity (BRS) recorded before and 50 min after CEX (40-min circuit, including seven stations of alternate aerobic/resistance exercises at 60-70% HR reserve) and non-exercise control (CONT) sessions. The study protocol was registered in a World Health Organization-accredited office (Trial registration RBR-7BWVPJ).RESULTS:SBP (Δ=−14.2±13.1 mmHg, p=0.0001), DBP (Δ=−5.2±8.2 mmHg, p= 0.04), Q (Δ=−2.2±1.5 L/min, p=0.0001), and BRS (Δ=−3.5±2.6 ms/mmHg; p=0.05) decreased after CEX as compared with the CONT session. By contrast, the HR increased (Δ=9.4±7.2 bpm, p<0.0001), and SVR remained stable throughout the postexercise period as compared with the CONT session (Δ=0.10±0.22 AU, p=0.14). We found no significant difference between the CEX and CONT with respect to the HRV indexes reflecting autonomic modulation.CONCLUSION:CEX induced PEH in the older individuals with prehypertension status. At least in the first 50 min, PEH occurred parallel to the decreased Q and increased HR, while SVR was not different. The changes in autonomic outflow appeared to be unrelated to the acute cardiac and hemodynamic responses.

Effects of exercise training on autonomic modulation and mood symptoms in patients with obstructive sleep apnea.

We evaluated the effects of exercise training (ET) on the profile of mood states (POMS), heart rate variability, spontaneous baroreflex sensitivity (BRS), and sleep disturbance severity in patients with obstructive sleep apnea (OSA). Forty-four patients were randomized into 2 groups, 18 patients completed the untrained period and 16 patients completed the exercise training (ET). Beat-to-beat heart rate and blood pressure were simultaneously collected for 5 min at rest. Heart rate variability (RR interval) was assessed in time domain and frequency domain (FFT spectral analysis). BRS was analyzed with the sequence method, and POMS was analyzed across the 6 categories (tension, depression, hostility, vigor, fatigue, and confusion). ET consisted of 3 weekly sessions of aerobic exercise, local strengthening, and stretching exercises (72 sessions, achieved in 40±3.9 weeks). Baseline parameters were similar between groups. The comparisons between groups showed that the changes in apnea-hypopnea index, arousal index, and O2 desaturation in the exercise group were significantly greater than in the untrained group (P<0.05). The heart rate variability and BRS were significantly higher in the exercise group compared with the untrained group (P<0.05). ET increased peak oxygen uptake (P<0.05) and reduced POMS fatigue (P<0.05). A positive correlation (r=0.60, P<0.02) occurred between changes in the fatigue item and OSA severity. ET improved heart rate variability, BRS, fatigue, and sleep parameters in patients with OSA. These effects were associated with improved sleep parameters, fatigue, and cardiac autonomic modulation, with ET being a possible protective factor against the deleterious effects of hypoxia on these components in patients with OSA.

Показатели вариабельности сердечного ритма и артериального давления у подростков с нервно-психическими нарушениями при выполнении нагрузочных проб

Целью настоящего исследования стало изучение особенностей вариабельности сердечного ритма (СР) и вариабельности артериального давления (АД) у подростков с клинически-подтверждённой нервно-психической патологией, при регистрации в условиях функциональной нагрузочной пробы. Методы. Методом спироартериокардиоритмографии проведено тестирование показателей сердечно-сосудистой системы в условиях функциональной нагрузочной пробы (в надетой спирометрической маске, с произвольным дыханием - модель лёгкой гиперкапнии/гипоксии) у учащихся специализированной школы для пациентов психиатрических клиник (на стадии ремиссии) (n = 61), и учащихся общеобразовательной школы (n = 197). Подростки из специализированной школы были разделены на две группы: пациенты с неврологическими диагнозами и последствиями органических поражений мозга (n = 35); пациенты с психическими расстройствами без органических поражений мозга (n = 26). Возраст учащихся из обеих школ составил 12,0-17,7 лет, выборки обеих школ были поделены на 5 возрастных диапазонов (12,0-13,5, 13,6-14,5, 14,6-15,5, 15,6-16,5 и 16,6-17,7 лет). В контрольной школе подростки были дополнительно разделены по полу. Результаты. В возрастных диапазонах 12,0-13,5, 13,6-14,5 и 14,6-15,5 лет статистически значимых различий между учащимися разных школ ни по одному показателю не обнаружено. В возрастном диапазоне 15,6-16,5 лет выявлены более высокие величины систолического и диастолического АД у подростков с неврологическими диагнозами и последствиями органических поражений мозга (по сравнению с контрольными группами). В возрастном диапазоне 16,6-17,7 лет у подростков с психическими расстройствами без органических поражений мозга обнаружены более высокие (по сравнению с контролем) величины стресс-индекса и более низкие (по сравнению с пациентами с неврологическими диагнозами) величины чувствительности спонтанного артериального барорефлекса (на уровне тенденции, p = 0,056). Заключение. Проведённые исследования показали, что по параметрам вариабельности СР и АД подростки с нервно-психической патологией не существенно отличаются от учащихся общеобразовательных школ. Повышение стресс-индекса у подростков с психопатологией без органических поражений мозга в возрасте 16,6-17,7 лет можно интерпретировать как коррелят повышения симпатической активности. У подростков с неврологическими заболеваниями, по-видимому, обнаружена более ранняя по сравнению с контролем манифестация юношеской предгипертензии (в 15,6-16,5 лет). The aim of this study was to assess characteristics of heart rate (HR) and blood pressure (BP) variability in adolescents with clinically confirmed neuropsychiatric pathology in the conditions of a functional test. Methods. The method of spiroarteriocardiorhythmography was used to test cardiovascular parameters during a functional stress test (voluntary breathing with a spirometric mask, a model of mild hypercapnia / hypoxia), in students of a specialized school for patients of psychiatric clinics (in remission) (n = 61) and students of a regular school (n = 197). Adolescents from a specialized school were divided into two groups: 1) patients with neurological diagnoses and consequences of organic brain damage (n = 35) and 2) patients with psychiatric disorders without organic brain damage (n = 26). The age of students from both schools was 12.0-17.7 years; samples of both schools were divided into 5 age ranges (12.0-13.5, 13.6-14.5, 14.6-15.5, 15.6-16.5 and 16.6-17.7 years). The adolescents from the control school were additionally subdivided by gender. Results. In the age ranges of 12.0-13.5, 13.6-14.5, and 14.6-15.5 years, no statistically significant differences were found between students from different schools in any parameters. In the age range of 15.6-16.5 years, adolescents with neurological diagnoses and consequences of organic brain damage had higher values of systolic and diastolic BP compared to the control groups. In the age range of 16.6-17.7 years, adolescents with psychiatric disorders without organic brain damage had higher values of the stress index than in the control groups, and a tendency towards lower values of spontaneous arterial baroreflex sensitivity compared to patients with neurological diagnoses (p = 0.056). Conclusion. Adolescents with neuropsychiatric pathologies did not significantly differ from students of regular schools in parameters of HR and BP variability. The increased stress index in adolescents with psychopathology without organic brain damage aged 16.6-17.7 years can be interpreted as a correlate of elevated sympathetic activity. Adolescents with neurological diseases apparently had an earlier onset of juvenile prehypertension (at 15.6-16.5 years) compared to the control.

Cardioautonomic control in healthy singleton and twin pregnancies.

In conjunction with significant cardiovascular adaptation, changes in cardioautonomic balance, specifically greater sympathetic activation and vagal withdrawal, are considered normal adaptations to healthy singleton pregnancy. Cardiovascular adaptation to twin pregnancy is more profound than that of singleton pregnancies; however, the changes in cardioautonomic control during multifetal gestation are unknown. To address this gap, beat-by-beat blood pressure (photoplethysmography) and heart rate (lead II electrocardiogram) were measured continuously in 25 twin pregnancies and 25 singleton pregnancies (matched for age, prepregnancy body mass index, and gestational age) during 10 min of rest. Data extracted from a 3- to 5-min period were used to analyze heart rate variability (HRV), blood pressure variability (BPV), cardiovagal baroreflex gain, and cardiac intervals as indicators of cardioautonomic control. Independent t tests were used to determine statistical differences between groups (α = 0.05), and the false rate discovery was determined to adjust for multiple comparisons. Resting heart rate was greater in twin compared with singleton pregnancies (91 ± 10 vs. 81 ± 10 beats/min; P = 0.001), but blood pressure was not different. Individuals with twin pregnancies had lower HRV, evidenced by lower standard deviation of R-R intervals (32 ± 11 vs. 47 ± 18 ms; P = 0.001), total power (1,035 ± 810 vs. 1,945 ± 1,570 ms2; P = 0.004), and high frequency power (224 ± 262 vs. 810 ± 806 ms2; P < 0.001) compared with singleton pregnancies. There were no differences in cardiac intervals, BPV, and cardiovagal baroreflex gain between groups. Our findings suggest that individuals with twin pregnancies have greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control is impacted during twin compared with singleton pregnancy.NEW & NOTEWORTHY Individuals with healthy twin pregnancies had lower overall heart rate variability compared with those with singleton pregnancies at similar gestational ages. These results suggest a greater sympathetic and reduced parasympathetic contribution to cardiac control in twin pregnancies. Baseline heart rate was elevated, while arterial pressure and spontaneous cardiovagal baroreflex gain were not different between groups. This was result of the upward resetting of the cardiovagal baroreflex during healthy twin pregnancy, thus maintaining arterial pressure.

CORP: Standardizing methodology for assessing spontaneous baroreflex control of muscle sympathetic nerve activity in humans.

The use of spontaneous bursts of muscle sympathetic nerve activity (MSNA) to assess arterial baroreflex control of sympathetic nerve activity has seen increased utility in studies of both health and disease. However, methods used for analyzing spontaneous MSNA baroreflex sensitivity are highly variable across published studies. Therefore, we sought to comprehensively examine methods of producing linear regression slopes to quantify spontaneous MSNA baroreflex sensitivity in a large cohort of subjects (n = 150) to support a standardized procedure for analysis that would allow for consistent and comparable results across laboratories. The primary results demonstrated that 1) consistency of linear regression slopes was considerably improved when the correlation coefficient was above -0.70, which is more stringent compared with commonly reported criterion of -0.50, 2) longer recording durations increased the percentage of linear regressions producing correlation coefficients above -0.70 (1 min = 15%, 2 min = 28%, 5 min = 53%, 10 min = 67%, P < 0.001) and reaching statistical significance (1 min = 40%, 2 min = 69%, 5 min = 78%, 10 min = 89%, P < 0.001), 3) correlation coefficients were improved with 3-mmHg versus 1-mmHg and 2-mmHg diastolic blood pressure (BP) bin size, and 4) linear regression slopes were reduced when the acquired BP signal was not properly aligned with the cardiac cycle triggering the burst of MSNA. In summary, these results support the use of baseline recording durations of 10 min, a correlation coefficient above -0.70 for reliable linear regressions, 3-mmHg bin size, and importance of properly time-aligning MSNA and diastolic BP. Together, these findings provide best practices for determining spontaneous MSNA baroreflex sensitivity under resting conditions for improved rigor and reproducibility of results.

CRF1 and CRF2 receptors in the lateral hypothalamus differently modulate the baroreflex function in unanesthetized rats

The lateral hypothalamus (LH) is a diencephalic structure that has been considered part of the central circuitry regulating the baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this hypothalamic area are poorly understood. Therefore, in the present study we investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the LH acting via local CRF1 and CRF2 receptors in cardiac baroreflex responses in unanesthetized rats. For this, the baroreflex activity was assessed using two approaches: i) the pharmacological approach via intravenous infusion of vasoactive agents, and ii) the sequence analysis technique that evaluates reflex responses during spontaneous arterial pressure variations. The sequence analysis technique indicated that LH treatment with the selective CRF1 receptor antagonist CP376395 decreased the baroreflex effectiveness index, whereas the selective CRF2 receptor antagonist antisauvagine-30 increased the reflex shortening of pulse interval during spontaneous arterial pressure decreases. However, the pharmacological approach did not indicate effect of the bilateral microinjection of either CP376395 or antisauvagine-30 into the LH in the tachycardia evoked by blood pressure decrease or the reflex bradycardia caused by blood pressure increase. Overall, these findings indicate that CRF neurotransmission within the LH controls baroreflex function during a narrow range of physiological arterial pressure variations. Besides, results provide evidence that CRF1 and CRF2 receptors in the LH oppositely modulate the spontaneous baroreflex activity through different mechanisms.

Peat smoke inhalation alters blood pressure, baroreflex sensitivity, and cardiac arrhythmia risk in rats

ABSTRACT Wildland fires (WF) are linked to adverse health impacts related to poor air quality. The cardiovascular impacts of emissions from specific biomass sources are however unknown. The purpose of this study was to assess the cardiovascular impacts of a single exposure to peat smoke, a key regional WF air pollution source, and relate these to baroreceptor sensitivity and inflammation. Three-month-old male Wistar-Kyoto rats, implanted with radiotelemeters for continuous monitoring of heart rate (HR), blood pressure (BP), and spontaneous baroreflex sensitivity (BRS), were exposed once, for 1-hr, to filtered air or low (0.38 mg/m3 PM) or high (4.04 mg/m3) concentrations of peat smoke. Systemic markers of inflammation and sensitivity to aconitine-induced cardiac arrhythmias, a measure of latent myocardial vulnerability, were assessed in separate cohorts of rats 24 hr after exposure. PM size (low peat = 0.4–0.5 microns vs. high peat = 0.8–1.2 microns) and proportion of organic carbon (low peat = 77% vs. high peat = 65%) varied with exposure level. Exposure to high peat and to a lesser extent low peat increased systolic and diastolic BP relative to filtered air. In contrast, only exposure to low peat elevated BRS and aconitine-induced arrhythmogenesis relative to filtered air and increased circulating levels of low-density lipoprotein cholesterol, complement components C3 and C4, angiotensin-converting enzyme (ACE), and white blood cells. Taken together, exposure to peat smoke produced overt and latent cardiovascular consequences that were likely influenced by physicochemical characteristics of the smoke and associated adaptive homeostatic mechanisms.

Instantaneous Cardiac Baroreflex Sensitivity: xBRS Method Quantifies Heart Rate Blood Pressure Variability Ratio at Rest and During Slow Breathing.

Spontaneous baroreflex sensitivity (BRS) is a widely used tool for the quantification of the cardiovascular regulation. Numerous groups use the xBRS method, which calculates the cross-correlation between the systolic beat-to-beat blood pressure and the R-R interval (resampled at 1 Hz) in a 10 s sliding window, with 0–5 s delays for the interval. The delay with the highest correlation is selected and, if significant, the quotient of the standard deviations of the R-R intervals and the systolic blood pressures is recorded as the corresponding xBRS value. In this paper we test the hypothesis that the xBRS method quantifies the causal interactions of spontaneous BRS from non-invasive measurements at rest. We use the term spontaneous BRS in the sense of the sensitivity curve is calculated from non-interventional, i.e., spontaneous, baroreceptor activity. This study includes retrospective analysis of 1828 measurements containing ECG as well as continues blood pressure under resting conditions. Our results show a high correlation between the heart rate – systolic blood pressure variability (HRV/BPV) quotient and the xBRS (r = 0.94, p < 0.001). For a deeper understanding we conducted two surrogate analyses by substituting the systolic blood pressure by its reversed time series. These showed that the xBRS method was not able to quantify causal relationships between the two signals. It was not possible to distinguish between random and baroreflex controlled sequences. It appears xBRS rather determines the HRV/BPV quotient. We conclude that the xBRS method has a potentially large bias in characterizing the capacity of the arterial baroreflex under resting conditions. During slow breathing, estimates for xBRS are significantly increased, which clearly shows that measurements at rest only involve limited baroreflex activity, but does neither challenge, nor show the full range of the arterial baroreflex regulatory capacity. We show that xBRS is exclusively dominated by the heart rate to systolic blood pressure ratio (r = 0.965, p < 0.001). Further investigations should focus on additional autonomous testing procedures such as slow breathing or orthostatic testing to provide a basis for a non-invasive evaluation of baroreflex sensitivity.

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P=0.001; second: 5.1±1.8 versus 3.8±1.1, P=0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P=0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27-2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P=0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P=0.002) and was associated with BPV after adjustment for mean blood pressure (r=0.26; P=0.005). First trimester baroreflex sensitivity did not differ between groups (P=0.23) and was not related to BPV (P=0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.

Cardiovascular system parameters in participants of Arctic expeditions.

A method of continuous heart rate (HR) and blood pressure (BP) recording was used for the evaluation of the cardiovascular system parameters in participants of short-term (<1 month) high-latitude expeditions, in comparison with the parameters of residents of Central Russia and the Arctic region. A dynamic examination of participants of Arctic expeditions (30 men, residents of middle-latitude regions, aged 46.7±1.7 years), workers permanently living in Central Russia (the Moscow region, 44 men, aged 46.7±1.0 years) and residents of the North (the Murmansk region, 35 men, aged 46.6±1.3 years) was performed. The authors used a spiroartheriocardiorythmograph allowing the parallel recording of HR, BP, spectral characteristics of HR variability (HRV) and the variability of systolic BP (sBP) and diastolic BP (dBP), cardiac performance parameters, and spontaneous baroreflex sensitivity (BRS). The parameters were recorded at rest, in a sitting position, over 2 min. The basic clinical parameters (HR, BP and cardiac performance) did not differ in the workers living in different climatic zones. However, the residents of the North demonstrated a lower total power (TP) of the dBP variability spectrum and a lower relative power of the high-frequency (HF) range in both the sBP and dBP variability spectra. The participants of expeditions to the North had a lower TP of the HRV spectrum (in comparison with both control groups) that did not change during the expeditions; BRS was reduced, while the TP of the sBP spectrum was increased in comparison with the corresponding parameters obtained from the residents of circumpolar regions, and decreased during the expedition in parallel with a decrease in the sBP values. The TP of both the sBP and dBP variability spectra, as well as the power of the HF range in these spectra, were similar in the participants of expeditions to those obtained from the residents of Central Russia, and they considerably surpassed the corresponding parameters in the northerners surveyed. The revealed peculiarities of the cardiovascular system in the participants of high-latitude expeditions can be considered as correlates of positive, and adequate in terms of the physiological value, adaptive shifts in the autonomous regulation of the cardiovascular system. Int J Occup Med Environ Health. 2020;33(6):819-28.

Abstract MP04: High Fat Diet Exposure Induces Epigenetic Modulation In The Brain Renin Angiotensin System

Cardiometabolic Diseases (CMD) are one of the highest causes of morbidity and mortality worldwide. In-utero, environmental insults can program brain’s progeny through changes in gene expression level affecting cardiometabolic functions. Methylation and demethylation of DNA take place by DNA methyltransferase (DNMT) and Ten eleven translocation (TET) enzymes, respectively. Expression of renin angiotensin system (RAS) on pre-autonomic neurons in the hypothalamus is believed to play a pivotal role in sympathetic activity controlling metabolic and blood pressure (BP) homeostasis. We hypothesize that perinatal exposure to high fat high sucrose diet (HFHSD) programs the brain RAS through methylation mechanisms that lead to autonomic dysfunction and hypersensitivity to CMD. C57BL6/J dams were fed HFHSD or regular diet (RD) and mated with RD sires. After weaning, offspring were raised on RD. Three-month old progeny underwent 24 h BP recording (telemetry), measurement of fasted blood glucose (FBG), assessment of autonomic function (pharmacological) and baroreflex sensitivity (sequence method). Mice were then sacrificed, and brains harvested for quantification of mRNA levels of DNMT, TET and RAS components in the hypothalamus. HFHSD-exposed male offspring showed elevation in systolic BP (140.2 ±1.9 vs. 131.2 ±2.4 mmHg, p=0.006), heart rate (611.3 ±7.8 vs 562.5 ±7 bpm, p&lt;0.0001) and FBG (172.7 ±6.3 vs. 142.6 ±6.3 mg/dl, p=0.018) but not females. Cardiac sympathetic activity was higher in HFHSD-exposed mice (-148 ±11.5 vs. -35.2 ±4.7 bpm, p&lt;0.05). Surprisingly, sympathetic vascular tone was only increased in HFHSD-exposed females (-64.6 ±5.7 vs. -36.7 ±2.9 mmHg, p&lt;0.05) while spontaneous baroreflex gain was improved in HFHSD-exposed males (5.3 ±0.7 vs. 2.6 ±0.4 msec/mmHg, p&lt;0.05). In the brain, DNMT1, DNMT3a and TET1, 2 and 3 mRNA expression were downregulated (p&lt;0.05) while AT 1a R and ACE2 genes were upregulated (p=0.02) in HFHSD-exposed mice. We conclude that perinatal exposure to a hypercaloric diet epigenetically programs the progeny’s brain through methylation leading to a pre-hypertensive and pre-diabetic phenotype associated with changes in the expression of RAS genes which could eventually result in increased susceptibility to CMD.

Cardiovascular evaluation of female rats with 6-OHDA-induced parkinsonism: Possible protection by ovarian hormones and participation of nitric oxide

AimsParkinson's disease (PD) is a neurological disorder caused by environmental and genetic factors, characterized by the death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to a decrease of dopamine in the striatum. In addition to motor symptoms, PD has several abnormalities, among which are cardiovascular changes, such as orthostatic and postprandial hypotension, and blood pressure lability. Studies demonstrate gender differences in PD pathogenesis, indicating that female hormones have a protective role against disease development. However, no studies examining cardiovascular changes in a female rat model of parkinsonism exist. Main methodsWistar female rats were subjected to ovariectomy (OVX) or sham surgery. After seven days, these animals were subjected to bilateral infusion of 6-hydroxydopamine (6-OHDA) or vehicle solution in their SNpc. On the 14th experimental day, a femoral artery catheterization was performed to record cardiovascular parameters after 24 h in conscious state. Analyses of cardiovascular variability and spontaneous baroreflex were performed. The nitrite (NO) concentration in the heart, thoracic aorta, abdominal aorta, and plasma was measured. Key findingsThe sham-6-OHDA group had no decrease in the mean arterial pressure compared to sham-saline group, whereas the OVX-6-OHDA group presented a baseline decrease in comparison to sham-6-OHDA. The OVX-6-OHDA group showed an NO increase in the heart and abdominal aorta, whereas the sham-6-OHDA group did not. The very low frequency variability component decreased in the sham-6-OHDA but not in the OVX-6-OHDA group. SignificanceWe suggest a cardiovascular protection by ovarian hormones in PD with a possible NO involvement.

Social defeat: Vagal reduction and vulnerability to ventricular arrhythmias

Previously, a sub-population of defeated anesthetized rats (Dlow) was characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF) at day 29 and autonomic alteration at day 30 after social challenge, while the other population (Dhigh) was similar to non-defeated (ND) animals. The aims of this study were to determine the time-course of autonomic dysfunction in awake animals, and whether Dhigh and/or Dlow were vulnerable to cardiac events. Defeated animals were exposed to four daily episodes of social defeats from day 1 to day 4. At day 30, anesthetized Dlow displayed decreased experimental and spontaneous reflex responses reflecting lower parasympathetic efficiency. In addition, Dlow but not Dhigh were characterized by left ventricular hypertrophy at day 30. Telemetric recordings revealed that Dlow had increased low frequency-to-high frequency ratio (LF/HF) and diastolic (DBP) and systolic (SBP) blood pressure, associated with decreased HF and spontaneous baroreflex responses (BRS) from day 3 to day 29. LF/HF, DBP and SBP recovered at day 5, and HF and BRS recovered at day 15 in Dhigh. Ventricular premature beats (VPBs) occurred in Dlow and Dhigh animals from day 5. Time course of VBP fluctuations in Dhigh mirrored that of HF and BRS, but not that of LF/HF, DBP and SBP.These results suggest that a psychosocial stress associated to low serum BDNF levels can lead to vulnerability to persistent autonomic dysfunction, cardiac hypertrophy and ventricular ectopic beats. The parasympathetic recovery seen in Dhigh may provide protection against cardiac events in this population.