Search

Background: Heart failure with reduced ejection fraction (HFrEF) is associated with reduced cardiac β-adrenergic signal transduction in response to chronic elevations in neurally released and circulating norepinephrine. Whether elevations in muscle sympathetic nerve activity (MSNA) are accompanied by attenuated α-adrenoceptor-mediated vasoconstriction remains unclear. Therefore, the objective of the current work was to compare transduction of sympathetic firing into blood pressure (BP) in treated patients with HFrEF and healthy controls.Methods: Twenty-three treated patients with HFrEF (4 females, left ventricular ejection fraction: 28±2%) and 22 healthy controls (6 females) underwent a 7-minute resting measurement of continuous beat-to-beat BP (finger photoplethysmography), heart rate (electrocardiography), and MSNA (microneurography). Sympathetic-BP transduction was quantified using both signal averaging, whereby the BP response to each MSNA burst was serially tracked over 15 cardiac cycles and averaged to derive the peak change in BP, and cross-spectral analysis of low-frequency (0.04-0.15 Hz) MSNA and BP oscillations.Results: Compared with controls, patients with HFrEF had less sympathetic-BP transduction (0.7±0.3 versus 0.2±0.3 mm Hg; P<0.01), and lower low-frequency oscillations in MSNA (120±56 versus 64±32 arbitrary units2; P<0.01) and BP (3.1±1.6 versus 2.0±1.7 mm Hg2; P<0.01). In subgroup analysis, resting sympathetic-BP transduction was lower in patients with HFrEF with normal resting MSNA compared to healthy controls (0.7±0.3 versus 0.4±0.3 mm Hg; P=0.01) and further attenuated (0.1±0.1 mm Hg; P=0.03) in patients with HFrEF with elevated resting MSNA.Conclusions: Treated HFrEF is associated with lower sympathetic-BP transduction, even when MSNA is not elevated, and diminishes further with disease progression. These adaptations may serve to limit the adverse consequences of oscillatory surges in sympathetic vasoconstrictor discharge on stroke volume. [ABSTRACT FROM AUTHOR]

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18-78 years [mean±SD]) and 260 female (age: 37±18; range: 18-81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min-1; P<1×10-19; 106±11/66±8 versus 116±7/68±9 mm Hg; P<0.01) but converged thereafter (38±11 versus 35±12 bursts·min-1; P=0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P>0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, -4 to 5) and 12 (95% CI, 6-16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women. [ABSTRACT FROM AUTHOR]

Background: Reflected arterial waves contribute to left ventricular (LV) afterload. Heart failure patients with reduced ejection fraction (HFrEF) are afterload sensitive and sympathetically activated. We tested the hypothesis that HFrEF patients exhibit a positive relationship between sympathetic vasoconstrictor discharge and aortic wave reflection.Methods: Sixteen treated patients with HFrEF (61 ± 9 years of age, left ventricular ejection fraction 30 ± 7%, 3 women) and 16 similar-aged healthy control subjects (57 ± 7 years of age, 4 women) underwent noninvasive measurements of radial pulse waveforms (applanation tonometry) to calculate central blood pressures and aortic wave reflection characteristics: augmentation pressure (AP), augmentation index (AIx), and AIx corrected to a heart rate of 75 beats/min (AIx@75). Muscle sympathetic nerve activity (MSNA) burst frequency was recorded from the fibular nerve (microneurography).Results: HFrEF patients had higher AIx (26 ± 9 vs 17 ± 15%; P < .05) and MSNA burst frequency (48 ± 7 vs 39 ± 11 bursts/min; P < .05) and lower central diastolic pressure than control subjects (64 ± 8 vs 70 ± 9 mm Hg; P = 0.05). There were no between-group differences in heart rate, other measures of blood pressure (brachial and central; P > .05), AP (11 ± 5 vs 7 ± 8 mm Hg; P = 0.11), or AIx@75 (19 ± 9 vs 13 ± 11%,-P = 0.14). MSNA correlated positively with AP (r = 0.50; P < .05), AIx (r = 0.51; P < .05), and AIx@75 (r = 0.54; P < .05) in HFrEF patients but not in control subjects (r = 0.002-0.18; P > 0.49).Conclusions: In patients with HFrEF, but not similarly aged healthy subjects, indices of aortic wave reflection correlate positively with MSNA. By increasing LV afterload, such neurovascular coupling could impair LV performance and worsen heart failure symptoms. Therapies that attenuate neurogenic vasoconstriction may benefit HFrEF patients by diminishing arterial wave reflection. [ABSTRACT FROM AUTHOR]

Prior studies demonstrating clinical significance of noninvasive estimates of central blood pressure (BP) and pulse wave reflection have relied primarily on discrete resting measures. The aim of this study was to compare central BP and pulse wave reflection measures sampled during a single resting laboratory visit against those obtained under ambulatory conditions. The secondary aim was to investigate the reproducibility of ambulatory central BP and pulse wave reflection measurements. Forty healthy participants (21 males; 24 ± 3 years) completed three measurements of brachial artery pulse wave analysis (Oscar 2 with SphygmoCor Inside) in the laboratory followed by 24 hours of ambulatory monitoring. Seventeen participants repeated the 24-hour ambulatory monitoring visit after at least 1 week. Ambulatory measures were divided into daytime (9 AM–9 PM), nighttime (1 AM–6 AM), and 24-hour periods. Compared with laboratory measurements, central systolic BP, augmentation pressure, and augmentation index (with and without heart rate normalization) were higher (all P < .01) during daytime and 24-hour periods but lower during the nighttime period (all P < .001). The drop in nighttime brachial systolic BP was larger than central systolic pressure (Δ −20 ± 6 vs. −15 ± 6 mm Hg; P < .0001). Repeat ambulatory measurements of central BP and pulse wave reflection displayed good-to-excellent intraclass correlation coefficients (r = 0.58–0.86; all P < .01), although measures of pulse wave reflection had higher coefficients of variation (14%–41%). The results highlight absolute differences in central BP and pulse wave reflection between discrete laboratory and ambulatory conditions. The use of ambulatory measures of central BP and pulse wave reflection warrant further investigation for clinical prognostic value. [ABSTRACT FROM AUTHOR]

Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity. Polysomnography identified 24 as having either no or mild obstructive sleep apnea (apnea-hypopnea index <15 events/h) and 24 with moderate-to-severe obstructive sleep apnea (apnea-hypopnea index >15 events/h). Burst incidence correlated significantly with arousal index (r=0.53; P<0.001), minimum oxygen saturation (r=-0.43; P=0.002), apnea-hypopnea index (r=0.41; P=0.004), age (r=0.36; P=0.013), and body mass index (r=0.33; P=0.022) but not with oxygen desaturation index (r=0.28; P=0.056). Arousal index was the single strongest predictor of muscle sympathetic nerve activity burst incidence, present in all best subsets regression models. The model with the highest adjusted R2 (0.456) incorporated arousal index, minimum oxygen saturation, age, body mass index, and oxygen desaturation index but not apnea-hypopnea index. An apnea- and hypoxia-independent effect of sleep fragmentation on sympathetic discharge during wakefulness could contribute to intersubject variability, age-related increases in muscle sympathetic nerve activity, associations between sleep deprivation and insulin resistance or insomnia and future cardiovascular events, and residual adrenergic risk with persistence of hypertension should therapy eliminate obstructive apneas but not arousals. [ABSTRACT FROM AUTHOR]