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.

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.

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.

Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults.

We and others have previously shown that COVID-19 results in vascular and autonomic impairments in young adults. However, the newest variant of COVID-19 (Omicron) appears to have less severe complications. Therefore, we investigated whether recent breakthrough infection with COVID-19 during the Omicron wave impacts cardiovascular health in young adults. We hypothesized that measures of vascular health and indices of cardiac autonomic function would be impaired in those who had the Omicron variant of COVID-19 when compared with controls who never had COVID-19. We studied 23 vaccinated adults who had COVID-19 after December 25, 2021 (Omicron; age, 23 ± 3 yr; 14 females) within 6 wk of diagnosis compared with 13 vaccinated adults who never had COVID-19 (age, 26 ± 4 yr; 7 females). Macro- and microvascular function were assessed using flow-mediated dilation (FMD) and reactive hyperemia, respectively. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx). Heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) were assessed as indices of cardiac autonomic function. FMD was not different between control (5.9 ± 2.8%) and Omicron (6.1 ± 2.3%; P = 0.544). Similarly, reactive hyperemia (P = 0.884) and arterial stiffness were not different between groups (e.g., cfPWV; control, 5.9 ± 0.6 m/s and Omicron, 5.7 ± 0.8 m/s; P = 0.367). Finally, measures of HR variability and cardiac BRS were not different between groups (all, P > 0.05). Collectively, these data suggest preserved vascular health and cardiac autonomic function in young, otherwise healthy adults who had breakthrough cases of COVID-19 during the Omicron wave.NEW & NOTEWORTHY We show for the first time that breakthrough cases of COVID-19 during the Omicron wave does not impact vascular health and cardiac autonomic function in young adults. These are promising results considering earlier research showing impaired vascular and autonomic function following previous variants of COVID-19. Collectively, these data demonstrate that the recent Omicron variant is not detrimental to cardiovascular health in young, otherwise healthy, vaccinated adults.

The impact of age, sex, cardio-respiratory fitness, and cardiovascular disease risk on dynamic cerebral autoregulation and baroreflex sensitivity.

BACKGROUND: Humans display an age-related decline in cerebral blood flow and increase in blood pressure (BP), but changes in the underlying control mechanisms across the lifespan are less well understood. We aimed to; (1) examine the impact of age, sex, cardiovascular disease (CVD) risk, and cardio-respiratory fitness on dynamic cerebral autoregulation and cardiac baroreflex sensitivity, and (2) explore the relationships between dynamic cerebral autoregulation (dCA) and cardiac baroreflex sensitivity (cBRS). METHODS: 206 participants aged 18-70 years were stratified into age categories. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound. Repeated squat-stand manoeuvres were performed (0.10 Hz), and transfer function analysis was used to assess dCA and cBRS. Multivariable linear regression was used to examine the influence of age, sex, CVD risk, and cardio-respiratory fitness on dCA and cBRS. Linear models determined the relationship between dCA and cBRS. RESULTS: Age, sex, CVD risk, and cardio-respiratory fitness did not impact dCA normalised gain, phase, or coherence with minimal change in all models (P > 0.05). cBRS gain was attenuated with age when adjusted for sex and CVD risk (young-older; ß = - 2.86 P < 0.001) along with cBRS phase (young-older; ß = - 0.44, P < 0.001). There was no correlation between dCA normalised gain and phase with either parameter of cBRS. CONCLUSION: Ageing was associated with a decreased cBRS, but dCA appears to remain unchanged. Additionally, our data suggest that sex, CVD risk, and cardio-respiratory fitness have little effect.

Post-exercise cardiac autonomic and cardiovascular responses to heart rate-matched and work rate-matched hypoxic exercise.

PURPOSE: This study investigated the effect of performing hypoxic exercise at the same heart rate (HR) or work rate (WR) as normoxic exercise on post-exercise autonomic and cardiovascular responses. METHODS: Thirteen men performed three interval-type exercise sessions (5 × 5-min; 1-min recovery): normoxic exercise at 80% of the WR at the first ventilatory threshold (N), hypoxic exercise (FiO2 = 14.2%) at the same WR as N (H-WR) and hypoxic exercise at the same HR as N (H-HR). Autonomic and cardiovascular assessments were conducted before and after exercise, both at rest and during active squat-stand manoeuvres (SS). RESULTS: Compared to N, H-WR elicited a higher HR response (≈ 83% vs ≈ 75%HRmax, p < 0.001) and H-HR a reduced exercise WR (- 21.1 ± 9.3%, p < 0.001). Cardiac parasympathetic indices were reduced 15 min after exercise and recovered within 60 min in N and H-HR, but not after H-WR (p < 0.05). H-WR altered cardiac baroreflex sensitivity (cBRS) both at rest and during SS (specifically in the control of blood pressure fall during standing phases) in the first 60 min after the exercise bout (p < 0.05). Post-exercise hypotension (PEH) did not occur in H-HR (p > 0.05) but lasted longer in H-WR than in N (p < 0.05). CONCLUSIONS: Moderate HR-matched hypoxic exercise mimicked post-exercise autonomic responses of normoxic exercise without resulting in significant PEH. This may relate to the reduced WR and the limited associated mechanical/metabolic strain. Conversely, WR-matched hypoxic exercise impacted upon post-exercise autonomic and cardiovascular responses, delaying cardiac autonomic recovery, temporarily decreasing cBRS and evoking prolonged PEH.

The impact of 2 years of high-intensity exercise training on a model of integrated cardiovascular regulation.

KEY POINTS: Heart rate variability, a common and easily measured index of cardiovascular dynamics, is the output variable of complicated cardiovascular and respiratory control systems. Both neural and non-neural control mechanisms may contribute to changes in heart rate variability. We previously developed an innovative method using transfer function analysis to assess the effect of prolonged exercise training on integrated cardiovascular regulation. In the present study, we modified and applied this to investigate the effect of 2 years of high-intensity training on circulatory components to tease out the primary effects of training. Our method incorporated the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. The dynamic Starling mechanism gain and arterial-cardiac baroreflex gain were significantly increased in the exercise group. These parameters remained unchanged in the controls. Conversely, neither group experienced a change in dynamic arterial elastance. The integrated cardiovascular regulation gain in the exercise group was 1.34-fold larger than that in the control group after the intervention. In these previously sedentary, otherwise healthy, middle-aged adults, 2 years of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity. ABSTRACT: Assessing the effects of exercise training on cardiovascular variability is challenging because of the complexity of multiple mechanisms. In a prospective, parallel-group, randomized controlled study, we examined the effect of 2 years of high-intensity exercise training on integrated cardiovascular function, which incorporates the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. Sixty-one healthy participants (48% male, aged 53 years, range 52-54 years) were randomized to either 2 years of exercise training (exercise group: n = 34) or control/yoga group (controls: n = 27). Before and after 2 years, subjects underwent a 6 min recording of beat-by-beat pulmonary artery diastolic pressure (PAD), stroke volume index (SV index), systolic blood pressure (sBP) and RR interval measurements with controlled respiration at 0.2 Hz. The dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function were calculated by transfer function gain between PAD and SV index; SV index and sBP; and sBP and RR interval, respectively. Fifty-three participants (controls: n = 25; exercise group: n = 28) completed the intervention. After 2 years, the dynamic Starling mechanism gain (Group × Time interaction: P = 0.008) and the arterial-cardiac baroreflex gain (P = 0.005) were significantly increased in the exercise group but remained unchanged in the controls. There was no change in dynamic arterial elastance in either of the two groups. The integrated cardiovascular function gain in the exercise group increased 1.34-fold, whereas there was no change in the controls (P = 0.02). In these previously sedentary, otherwise healthy middle-aged adults, a 2 year programme of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity, without changing dynamic arterial elastance.

Influence of age and gender on the phase and strength of the relation between heart period and systolic blood pressure spontaneous fluctuations.

Aging affects baroreflex regulation. The effect of senescence on baroreflex control was assessed from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) through the HP-SAP gain, while the HP-SAP phase and strength are usually disregarded. This study checks whether the HP-SAP phase and strength, as estimated, respectively, via the phase of the HP-SAP cross spectrum (PhHP-SAP) and squared coherence function (K2HP-SAP), vary with age in healthy individuals and trends are gender-dependent. We evaluated 110 healthy volunteers (55 males) divided into five age subgroups (21-30, 31-40, 41-50, 51-60, and 61-70 yr). Each subgroup was formed by 22 subjects (11 males). HP series was extracted from electrocardiogram and SAP from finger arterial pressure at supine resting (REST) and during active standing (STAND). PhHP-SAP and K2HP-SAP functions were sampled in low-frequency (LF, from 0.04 to 0.15 Hz) and in high-frequency (HF, above 0.15 Hz) bands. Both at REST and during STAND PhHP-SAP(LF) showed a negative correlation with age regardless of gender even though values were more negative in women. This trend was shown to be compatible with a progressive increase of the baroreflex latency with age. At REST K2HP-SAP(LF) decreased with age regardless of gender, but during STAND the high values of K2HP-SAP(LF) were more preserved in men than women. At REST and during STAND the association of PhHP-SAP(HF) and K2HP-SAP(HF) with age was absent. The findings points to a greater instability of baroreflex control with age that seems to affect to a greater extent women than men. NEW & NOTEWORTHY Aging increases cardiac baroreflex latency and decreases the degree of cardiac baroreflex involvement in regulating cardiovascular variables. These trends are gender independent but lead to longer delays and asmaller degree of cardiac baroreflex involvement in women than in men, especially during active standing, with important implications on the tolerance to an orthostatic stressor.

Stimulation of the mesencephalic ventral tegmental area blunts the sensitivity of cardiac baroreflex in decerebrate cats.

We have examined for the first time whether electrical stimulation of the mesencephalic ventral tegmental area (VTA) or the substantia nigra (SN) was capable of suppressing cardiac baroreflex sensitivity in decerebrate cats. After decerebration was performed by electrocoagulation at the precollicular-premammillary level and inhalation anesthesia was stopped, the animals were able to show spontaneous motor activity intermittently. Electrical stimulations of the mesencephalic areas (the VTA and SN) for 30s were conducted with a monopolar tungsten microelectrode (current intensity of pulse trains, 50-100 µA; frequency, 40-50 Hz; pulse duration, 0.5-1.0 ms), without producing tibial motor discharge. Stimulation of the VTA evoked the significant increases in heart rate (HR, 12 ± 2 beats/min) and mean arterial blood pressure (MAP, 12 ± 3 mm Hg). When the baroreflex bradycardia and the slope of the cardiac baroreflex curve were examined using a pressor response with brief occlusion of the abdominal aorta, the VTA stimulation blunted both the baroreflex bradycardia and the maximal slope of the baroreflex MAP-HR curve by 63-74% in the same manner as spontaneously-evoked motor activity. In contrast, stimulation of the SN elicited no modulation of cardiac baroreflex. It is likely that stimulation of the mesencephalic VTA suppresses cardiac baroreflex sensitivity and has the similar features of the effects on the cardiac baroreflex function as those during spontaneously-evoked motor activity.

Sustained mild hypergravity reduces spontaneous cardiac baroreflex sensitivity.

Head-to-foot gravitational force >1G (+Gz hypergravity) augments venous pooling in the lower body and reduces central blood volume during exposure, compared with 1Gz. Central hypovolemia has been reported to reduce spontaneous cardiac baroreflex sensitivity. However, no investigations have examined spontaneous cardiac baroreflex sensitivity during exposure to sustained mild +Gz hypergravity. We therefore hypothesized that mild +Gz hypergravity would reduce spontaneous cardiac baroreflex sensitivity, compared with 1Gz. To test this hypothesis, we examined spontaneous cardiac baroreflex sensitivity in 16 healthy men during exposure to mild +Gz hypergravity using a short-arm centrifuge. Beat-to-beat arterial blood pressure (tonometry) and R-R interval (electrocardiography) were obtained during 1Gz and 1.5Gz exposures. Spontaneous cardiac baroreflex sensitivity was assessed by sequence slope and transfer function gain. Stroke volume was calculated from the arterial pressure waveform using a three-element model. All indices of spontaneous cardiac baroreflex sensitivity decreased significantly (up slope: 18.6±2.3→12.7±1.6ms/mmHg, P<0.001; down slope: 19.0±2.5→13.2±1.3ms/mmHg, P=0.002; transfer function gain in low frequency: 14.4±2.2→10.1±1.1ms/mmHg, P=0.004; transfer function gain in high frequency: 22.2±7.5→12.4±3.5ms/mmHg, P<0.001). Stroke volume decreased significantly (88±5→80±6ml, P=0.025). Moreover, although systolic arterial pressure variability increased, R-R interval variability did not increase. These results suggest that even mild +Gz hypergravity reduces spontaneous cardiac baroreflex sensitivity, increasing the risk of cardiovascular disturbance during the exposure.

Impaired cardiac baroreflex sensitivity predicts response to renal sympathetic denervation in patients with resistant hypertension.

OBJECTIVES: This study sought to evaluate cardiac baroreflex sensitivity (BRS) as a predictor of response to renal sympathetic denervation (RDN). BACKGROUND: Catheter-based RDN is a novel treatment option for patients with resistant arterial hypertension. It is assumed that RDN reduces efferent renal and central sympathetic activity. METHODS: Fifty patients (age 60.3 ± 13.8 years [mean ± SD mean systolic blood pressure (BP) on ambulatory blood pressure monitoring (ABPM) 157 ± 22 mm Hg, despite medication with 5.4 ± 1.4 antihypertensive drugs) underwent RDN. Prior to RDN, a 30-min recording of continuous arterial BP (Finapres; TNO-TPD Biomedical Instrumentation, Amsterdam, the Netherlands) and high-resolution electrocardiography (1.6 kHz in orthogonal XYZ leads) was performed in all patients under standardized conditions. Cardiac BRS was assessed by phase-rectified signal averaging (BRSPRSA) according to previously published technologies. Response to RDN was defined as a reduction of mean systolic BP on ABPM by 10 mm Hg or more at 6 months after RDN. RESULTS: Six months after RDN, mean systolic BP on ABPM was significantly reduced from 157 ± 22 mm Hg to 149 ± 20 mm Hg (p = 0.003). Twenty-six of the 50 patients (52%) were classified as responders. BRSPRSA was significantly lower in responders than nonresponders (0.16 ± 0.75 ms/mm Hg vs. 1.54 ± 1.73 ms/mm Hg; p < 0.001). Receiver-operator characteristics analysis revealed an area under the curve for prediction of response to RDN by BRSPRSA of 81.2% (95% confidence interval: 70.0% to 90.1%; p < 0.001). On multivariable logistic regression analysis, reduced BRSPRSA was the strongest predictor of response to RDN, which was independent of all other variables tested. CONCLUSIONS: Impaired cardiac BRS identifies patients with resistant hypertension who respond to RDN.