Spontaneous Cardiac Baroreflex Sensitivity Research Articles

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

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

Augmented resting beat-to-beat blood pressure variability in patients with chronic kidney disease.

Our aim was to test the hypothesis that patients with chronic kidney disease (CKD) would exhibit augmented resting beat-to-beat blood pressure variability (BPV) that is associated with poor clinical outcomes independent of mean blood pressure (BP). In addition, since the arterial baroreflex plays a critical role in beat-to-beat BP regulation, we further hypothesized that an impaired baroreflex control would be associated with an augmented resting beat-to-beat BPV. In 25 sedentary patients with CKD stages III-IV (62 ± 9years) and 20 controls (57 ± 10years), resting beat-to-beat BP (finger photoplethysmography) and heart rate (electrocardiography) were continuously measured for 10min. We calculated the standard deviation (SD), average real variability (ARV) and other indices of BPV. The sequence technique was used to estimate spontaneous cardiac baroreflex sensitivity. Compared with controls (CON), the CKD group had significantly increased resting BPV. The ARV (2.2 ± 0.6 versus 1.6 ± 0.5mmHg, P < 0.001; 1.6 ± 0.7 versus 1.3 ± 0.3mmHg, P = 0.039; 1.4 ± 0.5 versus 1.0 ± 0.2mmHg, P < 0.001) of systolic, diastolic and mean BP, respectively, was increased in CKD versus controls. Other traditional measures of variability showed similar results. The cardiac baroreflex sensitivity was lower in CKD compared with controls (CKD: 8.4 ± 4.5ms/mmHg versus CON: 14.0 ± 8.2ms/mmHg, P = 0.008). In addition, cardiac baroreflex sensitivity was negatively associated with BPV [systolic blood pressure (SBP) ARV; r = -0.44, P = 0.003]. In summary, our data demonstrate that patients with CKD have augmented beat-to-beat BPV and lower cardiac baroreflex sensitivity. BPV and cardiac baroreflex sensitivity were negatively correlated in this cohort. These findings may further our understanding about cardiovascular dysregulation observed in patients with CKD.

Oral Administration of Amiloride Does Not Affect Spontaneous Cardiac Baroreflex Sensitivity in Humans

Pre-clinical models suggested that administration of Amiloride at the carotid sinus antagonizes the acid-sensing ion channels (ASICS), an essential component of the mechanoelectrical transducer in the arterial baroreceptors, reducing cardiac baroreflex sensitivity and perturbing the homeostatic beat-to-beat blood pressure (BP) regulation. However, it is still undetermined whether these findings could be translated into humans. Therefore, we determined whether oral administration of Amiloride reduces the spontaneous cardiac baroreflex (cBRS) sensitivity and perturbs BP regulation in humans. Heart rate (HR; electrocardiography) and beat-to-beat BP (finger photoplethysmography) were continuously measured in 5 healthy men (32 ± 6 yrs) during at least 5 min in two different conditions: (1) Control (CTL) and (2) 3 h after of oral administration of Amiloride (AMD – 5 mg + 50 mg of hydrochlorothiazide), a non-selective antagonist of ASICs. Spontaneous cardiac BRS was determined for all sequences (three or more consecutive beats with corresponding increases or decreases in systolic BP and R-R interval) combined (cBRSall) and separately for up (cBRSup – increases in BP and R-R interval) and down (cBRSdown – decreases in BP and R-R interval) sequences. HR (AMD 65 ± 7 vs. CLT 63 ± 12 beats/min, P = 0.543), mean (AMD 88 ± 9 vs. CLT 88 ± 7 mmHg, P = 0.687), and systolic BP (AMD 126 ± 14 vs. 128 ± 11 mmHg, P = 0.717) were similar in both conditions. Likewise, spontaneous cBRSall (AMD 20 ± 9 vs. CTL 22 ± 6 ms/mmHg, P = 0.543), cBRSup (AMD 19 ± 10 vs. CTL 22 ± 6 ms/mmHg, P = 0.495,) and cBRSdown (AMD 21 ± 9 vs. CTL 21 ± 8 ms/mmHg, P = 0.937) were preserved after AMD administration. In summary, our preliminary results demonstrated that the non-selective antagonism of ASICS via oral administration of AMD did not affect spontaneous cardiac baroreflex sensitivity and BP regulation in humans. This is the full abstract presented at the American Physiology Summit 2023 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.

Spontaneous Cardiac Baroreflex Sensitivity in Young, Healthy Black and White Adults: Influence of Race and Sex

Background: Black (BL) individuals living in the United States are more likely to develop hypertension and cardiovascular disease compared to their White (WH) counterparts. However, studies investigating racial differences in blood pressure regulation and baroreflex sensitivity (BRS) are limited and have reported equivocal results. Furthermore, despite BL females also having a high prevalence of hypertension and cardiovascular disease, sex differences are often not considered. Additionally, baroreflex effectiveness index (BEI) is a newer measure used to estimate baroreflex function, yet studies have not examined the influence of sex or race on BEI. Therefore, the purpose of this project was to investigate the effects of both race and sex on cardiac BRS and BEI. We hypothesized that BL individuals would have lower cardiac BRS and BEI than WH individuals. Methods: We studied 88 young healthy adults, 28 BL males (21 ± 3 years; mean ± SD), 17 WH males (24 ± 4 years), 15 BL females (21 ± 3 years), and 28 WH females (23 ± 4 years). Heart rate (ECG) and beat-to-beat arterial blood pressure (finger photoplethysmography) were continuously recorded during a five-minute resting baseline. Cardiac BRS was measured using the Sequence Method, by identifying the gain of the relationship between systolic blood pressure and RRI from sequence(s) of three or more consecutive heartbeats in which systolic blood pressure and RRI change in the same direction. BEI was quantified by baroreflex-driven ramps relative to all systolic blood pressure ramps. Results: Cardiac BRS was significantly higher in BL individuals (31 ± 15 ms/mmHg) compared to WH individuals (25 ± 11 ms/mmHg; main effect of race, p = 0.02). Interestingly, post hoc comparisons revealed that this was only true within the males (p = 0.03), but not females (p = 0.63). However, there was no difference in cardiac BRS between males and females (main effect of sex, p = 0.35) and no interaction between sex and race (p = 0.27). There were also no effects of race (p = 0.65) or sex (p = 0.15) on BEI. Conclusion: These preliminary data suggest that, in contrast to our hypothesis, young BL individuals have higher cardiac BRS compared to WH individuals; an effect that is only present in males. In contrast, BEI was not influenced by race or sex. Collectively, our findings do not suggest that lower cardiac BRS plays a major role in the higher prevalence of cardiovascular disease in BL individuals. This is the full abstract presented at the American Physiology Summit 2023 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.

Attenuated cardiac autonomic function in humans with high-affinity hemoglobin and compensatory polycythemia.

During hypoxic exposure, humans with high-affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared with healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high-affinity hemoglobin [6 females, O2 partial pressure at 50% [Formula: see text] (P50) = 16 ± 1 mmHg] compared with 12 humans with typical affinity hemoglobin (6 F, P50 = 26 ± 1 mmHg). Participants breathed normal room air for a 10-min baseline, followed by 20 min of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 ([Formula: see text]) to ∼50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in 5-min periods throughout the hypoxia exposure, beginning with the last 5 min of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method and the time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high-affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure (normoxia: 7 ± 4 vs. 16 ± 10 ms/mmHg, hypoxia minutes 15-20: 4 ± 3 vs. 14 ± 11 ms/mmHg; group effect: P = 0.02, high-affinity hemoglobin vs. control, respectively). Heart rate variability calculated in both the time (standard deviation of the N-N interval) and frequency (low frequency) domains was lower in humans with high-affinity hemoglobin than in controls (all P < 0.05). Our data suggest that humans with high-affinity hemoglobin may have attenuated cardiac autonomic function.

Reliability of measuring resting spontaneous cardiac baroreflex sensitivity using short sampling durations in healthy humans: Impact of central blood volume mobilization

IntroductionCalculation of spontaneous cardiac baroreflex sensitivity (cBRS) is used commonly to quantify arterial baroreflex buffering of beat‐to‐beat changes in blood pressure (BP). Studies report large interindividual variability in resting cBRS, which may be exacerbated by the supine posture and the use of shorter sampling duration (1‐3 min). However, this has yet to be reported in humans. Therefore, the purpose of the present study was to examine the impact of sampling duration on the intratest reliability of resting cBRS in healthy subjects. To accomplish this, we sought to compare resting cBRS derived from a standard 10‐min epoch (control) with values sampled over 7, 5, 3, and 1 min epoch durations. In addition, we examined the impact of central blood volume (CBV) mobilization on intratest reliability of resting cBRS.MethodsIn 30 healthy subjects (28 men; 22±3yrs) beat‐to‐beat measurements of BP and heart rate were recorded for 10‐min during both sitting and supine position. The cBRS was derived by sequence technique. Randomly selected epochs of 1‐min, 3‐min, 5‐min and 7‐min were then compared to the 10‐min control. To calculate the relative and absolute reliability we analyzed the technical error of the measurement (TEM), the intraclass correlation coefficients (ICC), Bland‐Altman analysis and coefficient of variations (CV). To test the impact of CBV mobilization on resting cBRS, ten subjects were also randomized to a non‐hypotensive lower body negative pressure (LBNP) trial at ‐20mmHg.ResultscBRS was lower in the sitting position than in the supine position (P&lt;0.01). All cBRS values were similar between each sampling duration compared to the 10‐min control (P&gt;0.12). The ICC obtained for cBRS ranged from very good to excellent in the supine position, whereas in the sitting position values demonstrated excellent between‐sampling duration reliability. The absolute and relative TEM increased with a shorter sampling duration (Table 1). In the LBNP trial, no significant differences in cBRS were observed within sampling durations in the LBNP trial (P=0.27). No significant differences in cBRS were observed between supine LBNP, sitting and supine positions (P=0.17). During LBNP trial, TEM increased with shorter sampling durations [10 vs. 7‐min: 0.7 ms/mmHg (4%), 10 vs. 5‐min: 1.4 ms/mmHg (8%), 10 vs. 3‐min: 1.9 ms/mmHg (11%), 10 vs. 1‐min: 3.1 ms/mmHg (17%), which was similar to the sitting position when compared to the supine posture.ConclusionOur findings show that 1) reliability decreased progressively using the 3‐ and 1‐min sampling durations; 2) the sitting position provides more reliable measures than all epoch durations measured in the supine position and; 3) the increases in the limits of agreement with shorter durations were attenuated by supine LBNP, suggesting that a cardiopulmonary baroreflex mechanism may play a role in the level of variability in resting cBRS.

Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat-to-beat blood pressure variability in young adults.

Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain unknown. Herein, we tested the hypothesis that a potentiation of GABAergic synaptic transmission by diazepam would acutely increase resting beat-to-beat blood pressure variability. In 40 (17 females) young, normotensive subjects, resting beat-to-beat blood pressure (finger photoplethysmography) was continuously measured for 5-10 min, 60 min after the oral administration of either diazepam (10 mg) or placebo. The experiments were conducted in a randomized, double-blinded, and placebo-controlled design. Stroke volume was estimated from the blood pressure waveform (ModelFlow) permitting the calculation of cardiac output and total peripheral resistance. Direct recordings of muscle sympathetic nerve activity (MSNA, microneurography) were obtained in a subset of subjects (n = 13), and spontaneous cardiac and sympathetic baroreflex sensitivity were calculated. Compared with placebo, diazepam significantly increased the standard deviation of systolic blood pressure (4.7 ± 1.4 vs. 5.7 ± 1.5 mmHg, P = 0.001), diastolic blood pressure (3.8 ± 1.2 vs. 4.5 ± 1.2 mmHg, P = 0.007), and mean blood pressure (3.8 ± 1.1 vs. 4.5 ± 1.1 mmHg, P = 0.002), as well as cardiac output (469 ± 149 vs. 626 ± 259 mL/min, P < 0.001) and total peripheral resistance (1.0 ± 0.3 vs. 1.4 ± 0.6 mmHg/L/min, P < 0.001). Similar results were found using different indices of variability. Furthermore, diazepam reduced MSNA (placebo: 22 ± 6 vs. diazepam: 18 ± 8 bursts/min, P = 0.025) without affecting the arterial baroreflex control of heart rate (placebo: 18.6 ± 6.7 vs. diazepam: 18.8 ± 7.0 ms/mmHg, P = 0.87) and MSNA (placebo: -3.6 ± 1.2 vs. diazepam: -3.4 ± 1.5 bursts/100 Hb/mmHg, P = 0.55). Importantly, these findings were not impacted by biological sex. We conclude that GABAA receptors modulate resting beat-to-beat blood pressure variability in young adults.

Influence of Family History of Hypertension on Spontaneous Cardiac Baroreflex Sensitivity in Young Non‐Hispanic Black and White Men

The prevalence of hypertension is higher in non-Hispanic Black (BK) adults compared to White (WH) adults. Studies suggest impairments in cardiac baroreflex sensitivity (cBRS) contribute to the future development of hypertension. Previous work investigating the impact of race on cBRS have reported equivocal results when comparing BK and WH individuals. Notably, these studies did not consider the potential presence of a family history of hypertension (FHH) in the participants, which is important because young otherwise healthy adults with a positive FHH (+FHH) have been shown to exhibit a reduced cBRS compared to those without a FHH (-FHH). Therefore, our objective was to investigate the impact of FHH on cBRS in young healthy BK and WH adult men. We tested the hypothesis that cBRS would be lower in young BK and WH men with a +FHH compared to those with a -FHH. Twenty-nine young BK (21 ± 1 years, +FHH n = 14) and thirty-one WH (22 ± 1 years, +FHH n = 16) adult men that were well-matched for age, physical activity, and body mass index were studied. Resting heart rate (electrocardiogram) and arterial blood pressure (BP; finger photoplethysmography and automated sphygmomanometer) were measured continuously during a 10 min quiet supine resting period. The Sequence Technique (Nevrokard) was used to estimate spontaneous cBRS separately for up sequences (increases in systolic BP: increases in R-R interval), down sequences (decreases in systolic BP: decreases in R-R interval), and for all sequences combined (overall cBRS). Resting heart rate and BP were not significantly different between groups (P > 0.05). Overall cBRS was greater in BK men compared to WH men (BK: 29.8 ± 2.2 ms/mmHg vs. WH: 22.1 ± 1.4 ms/mmHg; P < 0.01). However, there was no effect of FHH on overall cBRS in either group (BK +FHH: 32.4 ± 2.9 ms/mmHg vs. BK -FHH: 27.4 ± 3.2 ms/mmHg; WH +FHH: 23.2 ± 2.2 ms/mmHg vs. WH -FHH: 20.9 ± 1.9 ms/mmHg; race x FHH, P = 0.60). Similar results were observed for up (race x FHH, P = 0.98) and down sequences (race x FHH, P = 0.37). Notably, the number of sequences were similar between all groups. In summary, these preliminary findings suggest that +FHH does not influence cBRS in young healthy BK and WH men. Furthermore, young healthy BK men have greater overall cBRS compared to WH men; an effect that appears to be independent of FHH status.

Spontaneous cardiac baroreflex sensitivity is enhanced during post-exercise ischemia in men but not in women.

To investigate the effect of isolated muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity (cBRS), and to characterize the potential sex-related differences in this interaction in young healthy subjects. 40 volunteers (20 men and 20 women, age: 22 ± 0.4year) were recruited. After 5-min rest period, the subjects performed 90s of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 3min of post-exercise ischemia (PEI). Beat-to-beat heart rate and arterial blood pressure were continuously measured by finger photopletysmography. Spontaneous cBRS was assessed using the sequence technique and heart rate variability was measured in time (RMSSD-standard deviation of the RR intervals) and frequency domains (LF-low and HF-high frequency power). Resting cBRS was similar between men and women. During PEI, cBRS was increased in men (Δ3.0 ± 1.1msmmHg- 1, P = 0.03) but was unchanged in women (Δ-0.04 ± 1.0msmmHg- 1, P = 0.97). In addition, RMSSD and HF power of heart rate variability increased in women (Δ7.4 ± 2.6ms, P = 0.02; Δ373.4 ± 197.3ms2; P = 0.04, respectively) and further increased in men (Δ26.4 ± 7.1ms, P < 0.01; Δ1874.9 ± 756.2ms2; P = 0.02, respectively). Arterial blood pressure increased from rest during handgrip exercise and remained elevated during PEI in both groups, however, these responses were attenuated in women. These findings allow us to suggest a sex-related difference in spontaneous cBRS elicited by isolated muscle metaboreflex activation in healthy humans.

Sex Differences in Cardiac Baroreflex Sensitivity after Isometric Handgrip Exercise.

This study aimed to investigate potential sex-related differences on spontaneous cardiac baroreflex sensitivity (cBRS) after acute isometric handgrip (IHG) exercise. Twenty men (age, 23 ± 3 yr) and 20 women (age, 24 ± 4 yr) randomly performed four sets of 2-min IHG exercise (two sets for each limb) at 30% maximal voluntary contraction (experimental) or 3% maximal voluntary contraction (sham). Beat-to-beat heart rate (HR) and arterial blood pressure (BP) were monitored using finger photoplethysmography before and 10, 20, and 30 min after IHG. Spontaneous cBRS was assessed via the sequence technique and cardiac autonomic modulation via time- and frequency-domain HR variability. After IHG, spontaneous cBRS increased during 10 min of recovery in men (Δ13% ± 5%, P = 0.03 vs rest) and increased further in women (Δ23% ± 4%, P < 0.01 vs rest; P = 0.04 vs men). During 20 and 30 min of recovery, cBRS returned to baseline in men but remained elevated in women. HR decreased 10 min after IHG in men (10 min: Δ-2 ± 1 bpm, P < 0.01 vs rest; 20 min: Δ-1 ± 1 bpm, P = 0.39 vs rest; 30 min: Δ1 ± 1 bpm, P = 0.31 vs rest) and throughout recovery in women (10 min: Δ-5 ± 1 bpm, P < 0.01 vs rest; 20 min: Δ-3 ± 1 bpm, P < 0.01 vs rest; 30 min: Δ-2 ± 1 bpm, P < 0.01 vs rest). Systolic BP increased 10 min after IHG and remained elevated during 20 min and 30 min in men (P < 0.05). In women, systolic BP increased during 10 min (P < 0.01) and returned to baseline during 20 and 30 min of recovery. Time-domain HR variability (root mean square of successive differences) was increased during recovery in men and women (P < 0.05). Sham had no effect on any variables. Acute IHG exercise increases cBRS and cardiac vagal activity in healthy young subjects, but the magnitude and the time course of changes in cBRS differ between men and women.

Muscle Metaboreflex Modulation of Spontaneous Cardiac Baroreflex Sensitivity: Does Sex Matter?

It is well established that during exercise, the arterial baroreflex is reset to operate around the prevailing blood pressure in an exercise intensity‐dependent manner. This exercise‐induced modulation of baroreflex function is mediated by central signals and by afferent signals arising from working skeletal muscle that are composed of mechanically and metabolically sensitive afferents. Previous studies in humans examining the influence of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) on cardiac baroreflex sensitivity (cBRS) have found equivocal results reporting increases, decreases, or no change in sensitivity. The reason behind these discrepancies could be attributable to variation in the methods used to assess baroreflex function, exercise modality and intensity, size of exercising muscle mass, and, less discussed, but also relevant, the inclusion of both men and women. This becomes important given a plethora of studies indicating that sex plays a pivotal role when it comes to blood pressure regulation. Given this, the aim of the present study was to investigate the effect of isolated muscle metaboreflex activation on cBRS and the potential sex‐related differences in this interaction. Forty healthy and physically active volunteers (20 men), aged 18–30 years were recruited. All women were non‐oral contraceptives users and performed experiments in the early follicular phase of the menstrual cycle. After 10 minutes rest period, the subjects performed 90s of isometric handgrip (IHG) at 40% of maximal voluntary contraction followed by 3‐min of post exercise ischemia (PEI) to isolate the muscle metaboreflex. Beat‐to‐beat heart rate (HR ‐ electrocardiography) and arterial blood pressure (finger photopletysmography) were continuously measured. Spontaneous cBRS was assessed for all combined sequences (Gainall), and also separately upward (Gainup) and downward (Gaindown) using the sequence technique. HR variability was measured in time (RMSSD ‐ standard deviation of the RR intervals) and frequency domains (LF – low and HF – high frequency power). Resting MBP was lower in women than men (P &lt; 0.01). MBP increased from rest during IHG and remained elevated during PEI in both men and women. However, the magnitude of these responses was greater in men. Resting cBRS was similar between men and women. During PEI, men exhibited an increase in cBRS (Gainall: Δ3.0 ± 1.1 ms mmHg‐1, P = 0.03; Gainup: Δ4.4 ± 2.1 ms mmHg‐1, P = 0.04; and Gaindown: Δ3.3 ± 1.4 ms mmHg‐1, P = 0.03). In contrast, cBRS was unchanged during PEI in women (Gainall: Δ0.6 ± 0.7 ms mmHg‐1, P = 0.10; Gainup: Δ0.3 ± 0.7 ms mmHg‐1, P = 0.27; and Gaindown: Δ0.2 ± 1.1 ms mmHg‐1, P = 0.43). At rest, HF and LF power were lower in women compared with men, whereas RMSSD and LF/HF ratio were similar. During PEI, men exhibited a highest increase in RMSSD and HF compared to women, while LF power was unchanged in both groups. In addition, LF/HF ratio decreased in men and was unchanged in women. These findings indicate that the muscle metaboreflex activation modulates spontaneous cBRS in a sex dependent manner.Support or Funding InformationBrazilian National Council of Scientific and Technological Development (CNPq); Foundation for Research Support of Federal District (FAPDF); Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Daily inspiratory muscle training lowers blood pressure and vascular resistance in healthy men and women.

What is the central question of this study? What impact does inspiratory muscle training have on systemic vascular resistance, cardiac output and baroreflex sensitivity in adult men and women? What is the main finding and its importance? Inspiratory muscle training exerts favorable effects on blood pressure, vascular resistance and perception of stress. This exercise format is well-tolerated and equally effective whether implemented in men or women. Previous work has shown that inspiratory muscle training (IMT) lowers blood pressure after a mere 6weeks, identifying IMT as a potential therapeutic intervention to prevent or treat hypertension. Here, we explore the effects of IMT on respiratory muscle strength and select cardiovascular parameters in recreationally active men and women. Subjects were randomly assigned to IMT (n=12, 75% maximal inspiratory pressure) or sham training (n=13, 15% maximal inspiratory pressure) groups and underwent a 6-week intervention comprising 30breathsday-1 , 5daysweek-1 . Pre- and post-training measures included maximal inspiratory pressure and resting measures of blood pressure, cardiac output, heart rate, spontaneous cardiac baroreflex sensitivity and systemic vascular resistance. We evaluated psychological and sleep status via administration of the Cohen-Hoberman inventory of physical symptoms and the Epworth sleepiness scale. Male and female subjects in the IMT group showed declines in systolic/diastolic blood pressures (-4.3/-3.9mmHg, P<0.025) and systemic vascular resistance (-3.5mmHgminl-1 , P=0.008) at week 6. There was no effect of IMT on cardiac output (P=0.722), heart rate (P=0.795) or spontaneous cardiac baroreflex sensitivity (P=0.776). The IMT subjects also reported fewer stress-related symptoms (pre- versus post-training, 12.5±8.5 versus 7.2±9.7, P=0.025). Based on these results, we suggest that a short course of IMT confers significant respiratory and cardiovascular improvements and parallel (modest) psychological benefits in healthy men and women.

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial

BackgroundDespite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. ObjectiveTo test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. MethodsThirteen healthy men (23±1yrs) were randomized across three experimental visits. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time-control visit was performed with the electrodes placed on tragus, but no current was applied (sham-T). Additionally, to avoid a placebo effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus – tLS). Beat-to-beat heart rate (HR) and blood pressure (BP) were monitored at rest, during stimulation (active, sham-T and tLS) and recovery. cBRS was measured via sequence technique. Both HR (HRV) and BP variability (BPV) were also measured. ResultsArterial BP and BPV were not affected by any active or sham protocols (P > 0.05). Resting HR and LF/HF ratio of HRV decreased (Δ–3.4 ± 1% and Δ–15 ± 12%, P < 0.05, respectively) and cBRS increased (Δ24 ± 8%, P < 0.05) during active tVNS, but were unchanged during both sham protocols. ConclusiontVNS acutely improves cBRS and autonomic modulation in healthy young men.

Epinephrine Does Not Influence Baroreflex Sensitivity During Lower Body Negative Pressure to Physiological Tolerance

BackgroundThe baroreflex plays an integral role in blood pressure maintenance by altering heart rate and sympathetic activity in response to changes in arterial pressure. Baroreflex sensitivity (BRS) has been shown to decrease linearly during progressive exposure to central hypovolemia as induced by lower body negative pressure (LBNP), and can be used as an index of decompensation status during hemorrhage. Circulating epinephrine is significantly elevated during high stress situations such as hemorrhage; however, it is unclear whether epinephrine influences BRS during progressive exposure to central hypovolemia. Based on previous work, we hypothesized epinephrine would attenuate any reduction in spontaneous cardiac baroreflex sensitivity during LBNP.MethodsTen young (35±3 yrs), healthy (BMI 24±1 kg/m2) men and women (6M/4F) underwent LBNP protocols on 2 separate days consisting of a 10‐min pre‐infusion baseline, 15‐min infusion period (randomized to saline or epinephrine, 0.1 μg/kg/min), 10‐min post‐infusion baseline, and 5 minutes of LBNP at −15, −30, −45, −60, −70, and −80 mmHg until the onset of presyncope (range= −30 to −80 mmHg). Presyncope was defined as a rapid decrease in systolic blood pressure greater than 15 mmHg, systolic blood pressure less than 80 mmHg, bradycardia, or voluntary termination due to presyncopal symptoms. Heart rate (HR; electrocardiogram) and blood pressure (BP; radial arterial catheter) were recorded continuously. Spontaneous cardiac BRS was determined using the sequence method (WinCPRS). Data are reported from both 10‐min baselines and from 1 minute at 20, 40, 60, 80, and 100 percent of each individual's total LBNP exposure time.ResultsWe observed no significant differences in total exposure time (1475±150 vs. 1415±79s; p=0.69) or cumulative stress index (820±135 vs. 699±69 min*mmHg; p=0.37) between saline and epinephrine visits, respectively. Baroreflex sensitivity did not change during post‐infusion baselines (ΔDown‐Down =−2±1 vs. −2±2 ms/mmHg; saline vs. epinephrine, respectively; p=0.09). Baroreflex sensitivity was significantly reduced with LBNP (p&lt;0.01 main effect of LBNP). There was no difference between the change in baroreflex sensitivity during LBNP with saline or epinephrine infusion (ΔDown‐Down =−14±4 vs. −8±4 ms/mmHg, p=0.17).ConclusionsConsistent with previous work, spontaneous cardiac baroreflex sensitivity fell during LBNP. Contrary to our hypothesis, epinephrine infusion did not attenuate the fall in spontaneous cardiac baroreflex sensitivity observed during simulated blood loss. Because epinephrine did not alter the effect of LBNP on BRS, these data suggest that BRS may accurately reflect decompensation status during traumatic hemorrhage independent of elevated circulating epinephrine.Support or Funding InformationUS Army Medical Research and Materiel Command Contract W81XWH‐13‐2‐0038

Non‐invasive Vagus Nerve Stimulation Acutely Improves Blood Pressure Control in a Placebo Controlled Study

BackgroundDespite positive outcomes across a variety of disease states, invasive vagus nerve stimulation (VNS) has been associated with adverse side‐effects. Given this, non‐invasive VNS (tVNS) via the auricular branch of the vagus nerve (ABVN) has been proposed as an alternative approach. However, the mechanisms underlying these positive outcomes remain unclear. Therefore, we controlled the sensory effects (placebo) to investigate if tVNS acutely improves blood pressure (BP) control.MethodsThirteen healthy men (23±1yrs) were randomized across three experimental visits in a random order. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time‐ control visit was performed with the electrodes placed on tragus, but no current was applied (sham‐T). Additionally, to avoid a confounding sensory effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus – sham‐L). Before interventions were applied, we inform to subjects that both active tVNS and sham‐L would not cause any harm. Beat‐to‐beat heart rate (HR) and BP were monitored at rest, during tVNS (active, sham‐T and sham‐L) and recovery. Spontaneous cardiac baroreflex sensitivity (cBRS) was measured via sequence technique. Both HR (LF/HF) and BP variability (BPV) were also measured.ResultsArterial BP and BPV were not affected by any active or sham protocols (P&gt;0.05). HR and LF/HF ratio decreased (Δ–3.4±1% and Δ–17±10%, P&lt;0.05, respectively) and cBRS increased (Δ20±7%, P&lt;0.05) only during active tVNS, but were unchanged during both sham protocols (P&gt;0.05).ConclusionThe results of the present study provide evidence that tVNS acutely improves neural control of BP in healthy young men. These findings allow us to suggest that spontaneous cBRS and cardiac sympathovagal balance could play a role in the mechanisms involved in previously reported beneficial outcomes caused by tVNS. Future studies are needed to confirm these findings in older and diseased populations.Support or Funding InformationJ.L.S., A.L.T., P.M.M. have been supported by scholarships from Coordination for the Improvement of Higher Education Personnel (CAPES).

Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naïve Type 2 Diabetes following Equivalent Weight Loss.

Background and Purpose: Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss.Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n = 15), impaired glucose tolerant (IGT, n = 24), and newly-diagnosed T2D (n = 15) consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate) for 4-months. The three groups were matched for baseline age (56 ± 1 years), body mass index (BMI, 32.9 ± 0.7 kg/m2), and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography), spontaneous cardiac baroreflex sensitivity (BRS), and oral glucose tolerance test.Results: Weight loss averaged −7.5 ± 0.8, −8.1 ± 0.5, and −8.0 ± 0.9% of body weight in NGT, IGT, and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0−120) compared to NGT and IGT (group effect, P <0.001). Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group × time, P = 0.04). The magnitude of reduction in MSNA (−7 ± 3, −8 ± 4, −15 ± 4 burst/100 hb, respectively) and whole-body norepinephrine spillover rate (−28 ± 8, −18 ± 6, and −25 ± 7%, respectively), time effect both P <0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0−120 was independently associated with reduction in arterial norepinephrine concentration, whilst Δ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA.Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance. Attenuation of hyperinsulinemia and hyperlipidemia, rather than glycemic indices, is associated with reduction in SNS activity following weight loss intervention.

Abstract 081: Obesity-related Reductions in Cardiac Baroreflex Sensitivity and Higher 24-hour Blood Pressure Variability Are Not Related to Carotid Artery and Aortic Stiffness in Young And Middle-aged Adults

Alterations in cardiac baroreflex sensitivity (BRS) and 24-hr blood pressure variability (24-hr BPV) are independent predictors of increased cardiovascular disease (CVD) risk, and occur in individuals with obesity. Obese humans are also likely to have a higher large elastic artery stiffness compared with normal-weight individuals. While an increase in stiffness of carotid and aortic arteries, the anatomical sites where baroreceptors reside, may likely be responsible in part for the decline in cardiac BRS with advancing age in adults, it remains unclear whether 1) elevated carotid and aortic stiffness are also directly associated with obesity-associated reductions in cardiac BRS in young/middle-aged individuals, and 2) if reduced BRS with obesity is associated with elevated 24hr BPV. We tested the hypothesis that lower BRS would be associated with higher carotid and aortic stiffness and 24hr BPV in young and middle-aged individuals with obesity. In a cross-sectional design, 22 normal-weight (body mass index, BMI 24.5 ± 0.6 kg/m 2 ; age 35±2 yrs; 8M/14F) and 22 obese (BMI 34.2 ± 1.1 kg/m 2 ; age 39 ± 2 yrs; 8M/14F) individuals underwent measures of spontaneous cardiac BRS (sequence technique), carotid artery β-stiffness (carotid tonometry and B-mode ultrasound of common carotid artery), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), and 24-hr-systolic BPV (24 hr ambulatory BP monitoring). A significant relation between cardiac BRS and 24-hr systolic BPV (r=-0.42, P&lt;0.01) was corroborated by lower cardiac BRS (11.7±1.2 vs. 16.8±1.7 ms/mmHg, P&lt;0.05) and higher 24-hr BPV (12.4±0.6 vs. 10.1±0.4 mmHg SD, P&lt;0.05) among obese compared with normal-weight subjects. In contrast, carotid β-stiffness (7.8±0.6 vs. 6.9±0.4 U, P&gt;0.05) and CFPWV (745±71 vs. 611±19 cm/s, P=0.07) were not significantly different between groups despite greater average 24-hr systolic BP in the obese vs. normal weight subjects (127±2 vs. 118±1 mmHg, P&lt;0.05). These preliminary data suggest that an increase in carotid artery and aortic stiffness may not precede the decline in cardiac BRS and increase in 24hr BPV in young and middle-aged obese individuals, suggesting non-arterial stiffness related mechanisms for obesity-related reductions in cardiac BRS.

Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans.

The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low‐dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5‐min normoxia (~99% SpO2), followed by 5‐min hypoxia (~84% SpO2). Blood pressure (intra‐arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P < 0.01). Using the spectrum analysis approach, the fall in scBRS with hypoxia was attenuated with infusion of low‐dose dopamine (P < 0.01). The decrease in baroreflex sensitivity to rising pressures (scBRS “up‐up”) was also attenuated with low‐dose dopamine (P < 0.05). However, dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS “down‐down”; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low‐dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes.

Dynamic Modulation of Spontaneous Cardiac Baroreflex Sensitivity to Changes in Workloads in Humans

The arterial baroreflex plays important role in cardiovascular regulations during exercise. Previous studies showed that the spontaneous sensitivity of the cardiac component of arterial baroreflex (SBRS) is progressively attenuated with increasing workloads of dynamic exercise. However, dynamic modulation of SBRS to changes in workloads is unknown. PURPOSE: We aimed to investigate the amplitude response and phase response of SBRS during cycling exercise with sinusoidally-varying workload. METHODS: We studied 8 healthy male volunteers. After 5 minutes of resting measurements, the subjects performed cycling exercise at 50 W for 5 minutes. Then the workload was changed in a sinusoidal pattern between 30 W to 70 W for 32 minutes. The periods of sinusoidal workload were set to 4, 8 and 16 minutes. Subjects performed each of those three sinusoidal load exercise on separate days in random order. SBRS was evaluated as the slopes of the linear relations between R-R interval and systolic arterial blood pressure (SAP) during spontaneous sequences of at least three consecutive beats when SAP and R-R interval changed in the same directions. SBRS for all sequences were superimposed every periods of sinusoidal load and fitted to a sine model using the least-squares error approach to calculate amplitude response and phase response. RESULTS: During sinusoidal exercise, SBRS changed sinusoidally with the change of workload. The amplitude response of SBRS for 4, 8 and 16 minutes periods were 1.4 ± 0.3, 1.4 ± 0.2, and 1.2 ± 0.3 msec/mmHg, respectively and were not significantly different (p > 0.05). The phase lag of the SBRS from the sinusoidally-varying workload for 4, 8 and 16 minutes periods were 20.4 ± 4.2, 17.4 ± 4.3, and 3.6 ± 4.2 degrees, respectively. The phase lag of the SBRS in 16 minutes period was significantly smaller compared to 4 minutes period (p < 0.05). CONCLUSIONS: We conclude that the arterial baroreflex control of heart periods is modulated continuously in response to changes in workload. When workload changes fast, the modulation of SBRS delays from the changes in workloads. However, SBRS is modulated with almost no delay in response to relatively slow changes in workloads. We suggest that the dynamic modulation of the SBRS is one of the mechanisms to regulate cardiovascular responses in accordance with changes in workloads.

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, P<0.001). The 8 week exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=−0.65, P=0.044, adjusted for changes in MAP). Age- and endurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.