Cardiac Baroreflex Sensitivity Research Articles

Does a single oral administration of amiloride affect spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults?

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: 1) after 3 h of oral administration of placebo (PLA, 10 mg of methylcellulose within a gelatin capsule) and 2) after 3 h of oral administration of AMD (10 mg). Visits were separated for at least 48 h. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared with PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults.NEW & NOTEWORTHY Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults.

Cerebral homeostasis and orthostatic responses in residents of the highest city in the world

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. Healthy male participants living at sea-level (LL; n = 15), 3800 m (HL3800m; n = 13) and 5100 m (HL5100m; n = 17), respectively, and CMS highlanders living at 5100 m (n = 31) were recruited. Middle cerebral artery mean blood flow velocity (MCAv), cerebral oxygen delivery (CDO2), mean blood pressure (MAP), heart rate variability and spontaneuous cardiac baroreflex sensitivity (cBRS) were assessed while sitting, initial 30 s and after 3 min of standing. Cerebral autoregulation index (ARI) was estimated (ΔMCAv%baseline)/ΔMAP%baseline) in response to the orthostatic challenge. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MCAv and LFpower negatively correlated with altitude but were not affected by CMS. CDO2 remained preserved. BRS was comparable across all altitudes, but lower with CMS. Within initial 30 s of standing, altitude and CMS correlated with a lesser ΔMAP while ARI remained unaffected. After 3 min standing, MCAv, CDO2 and cBRS remained preserved across altitudes. The LF/HF ratio increased in HL5100m compared to LL and HL3800m from sitting to standing. In contrary, CMS showed blunted autonomic nervous activation in responses to standing. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis remained overall preserved.

Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

The change in Baroreflex Regulation of Heart Rhythm after “Dry” Immersion Appears during Orthostasis, but not Lower Body Negative Pressure Test

The ratio of low-frequency (LF, ~0.1 Hz) waves of RR interval duration (RRI) and systolic blood pressure (SAP) reflects the cardiac baroreflex sensitivity (BRS). Gravitational unloading (GU) may alter BRS during the passive orthostatic test (HUT) and lower body negative pressure (LBNP) test. Both effects cause blood redistribution to the lower body, but HUT is accompanied by greater unloading of sinocarotid baroreceptors than LBNP and activation of the vestibulosympathetic reflex but GU effects on BRS in these tests have not been directly compared previously. In this study we tested the hypothesis that the effect of “dry” immersion (DI, on-ground model of GU) on BRS in the same subjects will be more pronounced during HUT than during LBNP, which causes a comparable decrease in stroke volume. Nine healthy men participated in two test sessions (before and after 7-day DI) consisting of five 3-min HUT (65°) and five 3-min LBNP (–35 mmHg) with averaging the parameters in each test. Wavelet analysis was used to determine the amplitude of the RRI and SAP waves in the range of 0.05–0.13 Hz. The amplitude of LF waves of SAP increased in both tests, after DI - more significantly in HUT. The amplitude of LF RRI waves decreased in the two tests; the degree of decrease did not differ between tests and did not change under the influence of DI. The α-coefficient (the ratio of the amplitudes of RRI and SAP LF waves) decreased equally in the two tests before DI, but after DI, the degree of α-coefficient reduction increased in HUT test but did not change in LBNP test. Thus, the effect of DI on BRS is evident in HUT, but not in LBNP, which may be explained by the more pronounced influence of HUT on the mechanisms of neural control of heart rhythm.

Sex difference in cardiac autonomic function in African American adults

African American (AA) individuals in the United States have the highest prevalence of hypertension, with an age-adjusted prevalence of 55.8% in AA men and 56.9% in women. Compared to other racial groups, the AA population also has a two- to three-fold higher mortality rate resulting from hypertension-related causes. Furthermore, AA men exhibit a higher mortality rate than AA women. Previous studies have demonstrated sex differences in some biological mechanisms linked to the increased cardiovascular disease risk in the AA population —such as impaired vascular function and elevated oxidative stress. However, it is unknown whether sex differences are present in baroreflex sensitivity (BRS) and heart rate variability (HRV), which are key mechanisms that may contribute to the pathogenesis and clinical outcomes of hypertension. Herein, we tested the hypothesis that young AA men exhibit impaired cardiac autonomic function (spontaneous BRS and HRV) compared to AA women. We studied 26 young normotensive AA adults (13 women) [Age (men: 22 ± 3; and women: 19 ± 1yr; mean ± SD, p = 0.03); BMI (men: 24 ± 3; and women: 24 ± 2 kg/m2; p = 0.92)]. Heart rate (HR; ECG) and beat-to-beat blood pressure (BP; finger plethysmography) were continuously recorded during 10 min of rest to assess HRV and cardiac BRS. Resting HR (men, 61 ± 8; and women: 65 ± 9 bpm; p = 0.18), diastolic BP (men, 66 ± 6; and women: 65 ± 5 mmHg; p = 0.48) and respiratory rate (men, 17 ± 3; and women, 17 ± 3 bpm; p = 0.97) were similar between the groups. Mean BP and systolic BP were higher in AA men, though within the normotensive range for both groups [mean BP (men: 84 ± 5; and women: 76 ± 5 mmHg; p = 0.001); SBP (men: 119 ± 4; and women: 103 ± 7 mmHg; p < 0.001)]. HRV [root mean square of successive differences between normal heartbeats (RMSSD); men, 113 ± 78; and women, 79 ± 43 ms; p = 0.18] and cardiac BRS (overall gain; men, 25 ± 13; and women, 28 ± 12 ms/mmHg; p = 0.66) were not different between groups. These results indicate that BRS and HRV, which are markers of cardiac autonomic regulation, do not differ based on sex among young normotensive African American individuals. Supported by: Kinesiology and Health Education UT Austin Start-up Account 19-2635-91; and TACSM 2023 Student Research Development Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiac autonomic function is preserved in young adults with major depressive disorder.

The prevalence of major depressive disorder (MDD) is highest in young adults and contributes to an increased risk of developing future cardiovascular disease (CVD). However, the underlying mechanisms remain unclear. The studies examining cardiac autonomic function that have included young unmedicated adults with MDD report equivocal findings, and few have considered the potential influence of disease severity or duration. We hypothesized that heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) would be reduced in young unmedicated adults with MDD (18-30 yr old) compared with healthy nondepressed young adults (HA). We further hypothesized that greater symptom severity would be related to poorer cardiac autonomic function in young adults with MDD. Heart rate and beat-to-beat blood pressure were continuously recorded during 10 min of supine rest to assess HRV and cardiac BRS in 28 HA (17 female, 22 ± 3 yr old) and 37 adults with MDD experiencing current symptoms of mild-to-moderate severity (unmedicated; 28 female, 20 ± 3 yr old). Neither HRV [root mean square of successive differences between normal heartbeats (RMSSD): 63 ± 34 HA vs. 79 ± 36 ms MDD; P = 0.14] nor cardiac BRS (overall gain, 21 ± 10 HA vs. 23 ± 7 ms/mmHg MDD; P = 0.59) were different between groups. In young adults with MDD, there was no association between current depressive symptom severity and either HRV (RMSSD, R2 = 0.004, P = 0.73) or cardiac BRS (overall gain, R2 = 0.02, P = 0.85). Taken together, these data suggest that cardiac autonomic dysfunction may not contribute to elevated cardiovascular risk factor profiles in young unmedicated adults with MDD of mild-to-moderate severity.NEW & NOTEWORTHY This study investigated cardiac autonomic function in young unmedicated adults with major depressive disorder (MDD). The results demonstrated that both heart rate variability and cardiac baroreflex sensitivity were preserved in young unmedicated adults with MDD compared with healthy nondepressed young adults. Furthermore, in young adults with MDD, current depressive symptom severity was not associated with any indices of cardiac autonomic function.

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.

Role of the autonomic nervous system in young, middle-aged, and older individuals with essential hypertension and sleep-related changes in neurocardiac regulation

Essential hypertension involves complex cardiovascular regulation. The autonomic nervous system function fluctuates throughout the sleep–wake cycle and changes with advancing age. However, the precise role of the autonomic nervous system in the development of hypertension during aging remains unclear. In this study, we characterized autonomic function during the sleep–wake cycle in different age groups with essential hypertension. This study included 97 men (53 with and 44 without hypertension) aged 30–79 years. They were stratified by age into young (< 40 years), middle-aged (40–59 years), and older (60–79 years) groups. Polysomnography and blood pressure data were recorded for 2 min before and during an hour-long nap. Autonomic function was assessed by measuring heart rate variability and blood pressure variability. Data were analyzed using t tests, correlation analyses, and two-way analysis of variance. During nonrapid eye movement (nREM), a main effect of age was observed on cardiac parasympathetic measures and baroreflex sensitivity (BRS), with the highest and lowest levels noted in the younger and older groups, respectively. The coefficients of the correlations between these measures and age were lower in patients with hypertension than in normotensive controls. The BRS of young patients with hypertension was similar to that of their middle-aged and older counterparts. However, cardiac sympathetic activity was significantly higher (p = 0.023) and BRS was significantly lower (p = 0.022) in the hypertension group than in the control group. During wakefulness, the results were similar although some of the above findings were absent. Autonomic imbalance, particularly impaired baroreflex, plays a more significant role in younger patients with hypertension. The nREM stage may be suitable for gaining insights into the relevant mechanisms.

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.

Greater post-exercise hypotension in healthy young untrained men after exercising in a hot compared to a temperate environment

This research examined the effects of exercising in a hot compared to a temperate environment on post-exercise hemodynamics in untrained men. We hypothesized exercise in a hot compared to a temperate environment would elicit greater post-exercise hypotension, and this would be attributable to higher cutaneous vascular conductance and sweat loss, and lower heart rate variability (HRV) and cardiac baroreflex sensitivity (cBRS). In a randomized counterbalanced order, 12 untrained healthy men completed two trials involving 40-min leg-cycling exercise at either 23 °C (CON) or 35 °C (HOT). Post-exercise participants rested supine for 60 min at 23 °C whilst hemodynamic and thermoregulatory measurements were assessed. Post-exercise hypotension was greater after exercising in a hot than a temperate environment as indicated by a lower mean arterial pressure at 60 min recovery (CON 83 ± 5 mmHg, HOT 78 ± 5 mmHg, Mean difference [95% confidence interval], −5 [–8, −3] mmHg). Throughout recovery, cutaneous vascular conductance was higher, and cBRS and HRV were lower after exercising in a hot than in a temperate environment (P < 0.05). Sweat loss was greater on HOT than on CON (P < 0.001). Post-exercise hypotension after exercising in the hot environment was associated with sweat loss (r = 0.66, P = 0.02), and changes in cutaneous vascular conductance (r = 0.64, P = 0.03), and HRV (Root mean square of the successive difference in R-R interval [RMSSD]) r=0.75, P = 0.01 and and log high frequency [HF] r=0.66, P = 0.02), but not cBRS (all, r ≤ 0.2, P > 0.05). Post-exercise hypotension was greater after exercise in a hot compared to a temperate environment and may be partially explained by greater sweat loss and cutaneous vascular conductance, and lower HRV.

Cardiovascular autonomic regulation correlates with cognitive performance in patients with a history of traumatic brain injury

Background and objectiveTraumatic brain injury (TBI) may afflict brain areas contributing to both cardiovascular autonomic regulation and cognitive performance. To evaluate possible associations between both functions in patients with a history of TBI (post-TBI-patients), we determined correlations between cardiovascular autonomic regulation and cognitive function in post-TBI-patients.MethodsIn 86 post-TBI-patients (33.1 ± 10.8 years old, 22 women, 36.8 ± 28.9 months after injury), we monitored RR intervals (RRI), systolic and diastolic blood pressures (BPsys, BPdia), and respiration (RESP) at rest. We calculated parameters of total cardiovascular autonomic modulation (RRI-standard-deviation (RRI-SD), RRI-coefficient-of-variation (RRI-CV), RRI-total-powers), sympathetic (RRI-low-frequency-powers (RRI-LF), normalized (nu) RRI-LF-powers, BPsys-LF-powers) and parasympathetic modulation (root-mean-square-of-successive-RRI-differences (RMSSD), RRI-high-frequency-powers (RRI-HF), RRI-HFnu-powers), sympathetic-parasympathetic balance (RRI-LF/HF-ratios), and baroreflex sensitivity (BRS). We used the Mini-Mental State Examination and Clock Drawing Test (CDT) to screen the general global and visuospatial cognitive function, and applied the standardized Trail Making Test (TMT)-A assessing visuospatial abilities and TMT-B assessing executive function. We calculated correlations between autonomic and cognitive parameters (Spearman’s rank correlation test; significance: P < 0.05).ResultsCDT values positively correlated with age (P = 0.013). TMT-A values inversely correlated with RRI-HF-powers (P = 0.033) and BRS (P = 0.043), TMT-B values positively correlated with RRI-LFnu-powers (P = 0.015), RRI-LF/HF-ratios (P = 0.036), and BPsys-LF-powers (P = 0.030), but negatively with RRI-HFnu-powers (P = 0.015).ConclusionsIn patients with a history of TBI, there is an association between decreased visuospatial and executive cognitive performance and reduced parasympathetic cardiac modulation and baroreflex sensitivity with relatively increased sympathetic activity. Altered autonomic control bears an increased cardiovascular risk; cognitive impairment compromises quality of life and living conditions. Thus, both functions should be monitored in post-TBI-patients.

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.

Cardiovascular autonomic function and baroreflex sensitivity in drug-resistant temporal lobe epilepsy

ObjectiveTemporal lobe epilepsy (TLE) is often associated with autonomic manifestations. Sudden unexpected death in epilepsy (SUDEP) is a leading cause of mortality in epilepsy. Cardiac disturbances and autonomic dysfunction are the potential mechanisms behind SUDEP. Though heart rate variability (HRV) and autonomic function tests are well studied in drug-resistant temporal lobe epilepsy, there is a paucity of data on baroreflex sensitivity (BRS), a better marker of cardiac mortality in this population. We aimed to study the interictal cardiac autonomic function and BRS in people living with drug-resistant temporal lobe epilepsy compared to healthy controls. Materials and methodsThirty drug-resistant temporal lobe epilepsy (TLE) individuals and thirty healthy volunteers were recruited. Heart rate variability at rest, heart rate and blood pressure (BP) at rest, during deep breathing, postural change, BP response to isometric handgrip exercise, and baroreflex sensitivity were recorded in all study participants. The results were analyzed and compared between the two groups. ResultsCompared to controls, the resting heart rate, HRV, parasympathetic reactivity test, and BRS significantly differed in people living with drug-resistant TLE. Time-domain indices including SDNN (p < 0.001), RMSSD (p < 0.001), NN50 (p < 0.001), and pNN50 (p < 0.001) were significantly reduced in the patients compared to controls. In frequency-domain indices, the total power was reduced (p < 0.001) in drug-resistant TLE. The parasympathetic reactivity such as changes in heart rate during deep breathing (E: I) (p < 0.02) and postural change (30:15) (p < 0.005) were significantly reduced in the patients. Baroreflex sensitivity was also significantly reduced in the drug-resistant TLE group (p < 0.001). ConclusionThe present study findings are suggestive of parasympathetic dysfunction in drug-resistant TLE. Reduced HRV and BRS may increase the risk of SUDEP in people living with epilepsy.

Central command suppresses pressor-evoked bradycardia at the onset of voluntary standing up in conscious cats.

What is the central question of this study? Standing up can cause hypotension and tachycardia. Accumulated evidence poses the simple question, does the cardiac baroreflex operate at the onset of standing up? If the cardiac baroreflex is suppressed, what mechanism is responsible for baroreflex inhibition? What is the main finding and its importance? In cats, we found blunting of cardiac baroreflex sensitivity in the pressor range at the onset of voluntary hindlimb standing, but not of passive hindlimb standing. This finding suggests that central command suppresses pressor-evoked bradycardia at the onset of standing up, probably in advance, to prevent or buffer orthostatic hypotension. It remains unclear whether cardiac baroreflex function is preserved or suppressed at the onset of standing up. To answer the question and, if cardiac baroreflex is suppressed, to investigate the mechanism responsible for the suppression, we compared the sensitivity of the arterial cardiac baroreflex at the onset of voluntary and passive hindlimb standing in conscious cats. Cardiac baroreflex sensitivity was estimated from the maximal slope of the baroreflex curve between the responses of systolic arterial blood pressure and heart rate to a brief occlusion of the abdominal aorta. The systolic arterial blood pressure response to standing up without aortic occlusion was greater in the voluntary case than in the passive case. Cardiac baroreflex sensitivity was clearly decreased at the onset of voluntary standing up compared with rest (P=0.005) and the onset of passive standing up (P=0.007). The cardiac baroreflex sensitivity at the onset of passive standing up was similar to that at rest (P=0.909). The findings suggest that central command would transmit a modulatory signal to the cardiac baroreflex system during the voluntary initiation of standing up. Furthermore, the present data tempt speculation on a close relationship between central inhibition of the cardiac baroreflex and the centrally induced tachycardiac response to standing up.

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients’ response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes.

Impact of COVID-19 on cardiac autonomic function in healthy young adults: potential role of symptomatology and time since diagnosis.

Emerging evidence suggests that COVID-19 may affect cardiac autonomic function; however, the limited findings in young adults with COVID-19 have been equivocal. Notably, symptomology and time since diagnosis appear to influence vascular health following COVID-19, but this has not been explored in the context of cardiac autonomic regulation. Therefore, we hypothesized that young adults who had persistent symptoms following COVID-19 would have lower heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) compared with those who had COVID-19 but were asymptomatic at testing and controls who never had COVID-19. Furthermore, we hypothesized that there would be relationships between cardiac autonomic function measures and time since diagnosis. We studied 27 adults who had COVID-19 and were either asymptomatic (ASYM; n = 15, 6 females); 21 ± 4 yr; 8.4 ± 4.0 wk from diagnosis) or symptomatic (SYM; n = 12, 9 females); 24 ± 3 yr; 12.3 ± 6.2 wk from diagnosis) at testing, and 20 adults who reported never having COVID-19 (24 ± 4 yr, 11 females). Heart rate and beat-to-beat blood pressure were continuously recorded during 5 min of rest to assess HRV and cardiac BRS. HRV [root mean square of successive differences between normal heartbeats (RMSSD); control, 73 ± 50 ms; ASYM, 71 ± 47 ms; and SYM, 84 ± 45 ms; P = 0.774] and cardiac BRS (overall gain; control, 22.3 ± 10.1 ms/mmHg; ASYM, 22.7 ± 12.2 ms/mmHg; and SYM, 24.3 ± 10.8 ms/mmHg; P = 0.871) were not different between groups. However, we found correlations with time since diagnosis for HRV (e.g., RMSSD, r = 0.460, P = 0.016) and cardiac BRS (overall gain, r = 0.470, P = 0.014). These data suggest a transient impact of COVID-19 on cardiac autonomic function that appears mild and unrelated to persistent symptoms in young adults.NEW & NOTEWORTHY The potential role of persistent COVID-19 symptoms on cardiac autonomic function in young adults was investigated. We observed no differences in heart rate variability or cardiac baroreflex sensitivity between controls who never had COVID-19 and those who had COVID-19, regardless of symptomology. However, there were significant relationships between measures of cardiac autonomic function and time since diagnosis, suggesting that COVID-19-related changes in cardiac autonomic function are transient in young, otherwise healthy adults.

Hypobaric hypoxia and cardiac baroreflex sensitivity in young women.

We sought to determine the effects of prolonged moderate hypobaric hypoxia (HH) on cardiac baroreflex sensitivity (cBRS) in young women and whether these effects are a consequence of the reduced arterial oxygen (O2) tension and/or increased pulmonary ventilation in HH. We hypothesized that HH would reduce cBRS and that this effect would be counteracted by acute restoration of the inspiratory partial pressure of O2 ([Formula: see text]) and/or voluntary attenuation of pulmonary ventilation. Twelve healthy women (24.0 ± 4.2 yr) were studied before (day 0) and twice during a sojourn in a hypobaric chamber (∼8 h, day 1; 4 days, day 4) where barometric pressure corresponded to ∼3,500-m altitude. Minute ventilation (V̇e; pneumotachometer), heart rate (electrocardiogram), and arterial pressure (finger volume clamp method) were recorded. cBRS was calculated using transfer function analysis between systolic pressure and RR interval. Assessments were made during 1) spontaneous breathing and (in HH only), 2) controlled breathing (reducing V̇e by ∼1 to 2 L/min), and 3) breathing a hyperoxic gas mixture that normalized [Formula: see text]. During spontaneous breathing, HH decreased cBRS (12.5 ± 7.1, 8.9 ± 4.4, and 7.4 ± 3.0 ms/mmHg on days 0, 1, and 4, respectively; P = 0.018). The normalization of [Formula: see text] increased cBRS (10.6 ± 3.3 and 10.7 ± 6.1 ms/mmHg on days 1 and 4) in HH compared with values observed during spontaneous breathing (P < 0.001), whereas controlled breathing had no effect on cBRS (P = 0.708). These findings indicate that ongoing arterial chemoreflex activation by the reduced arterial O2 tension, independently of the hypoxic ventilatory response, reduces cBRS in young women exposed to extended HH.NEW & NOTEWORTHY We examined the effects of prolonged hypobaric hypoxia (corresponding to ∼3,500-m altitude) on cardiac baroreflex sensitivity (cBRS) in young women and investigated underlying mechanisms. We found that cBRS was reduced in hypoxia and that this reduction was attenuated by acute restoration of inspiratory oxygen partial pressure but not by volitional restraint of pulmonary ventilation. These findings help to elucidate the role of arterial chemoreflex mechanisms in the control of cBRS during hypobaric hypoxia in young women.

The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans.

A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n=51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R=-0.54, P<0.0001) and frequency (R=0.61, P<0.001) domains; there was a stronger relationship in the HT group (R=0.73) compared to the LT group (R=0.31) in the frequency domain (P=0.08), but no difference between groups in the time domain (HT: R=-0.73 vs. LT: R=-0.63; P=0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.