Paradoxical Muscle Sympathetic Reflex Activation in Human Heart Failure

Millar, Philip J.; Murai, Hisayoshi; Floras, John S.

doi:10.1161/circulationaha.114.010765

Cited by 61 publications

(85 citation statements)

References 48 publications

(70 reference statements)

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“…We speculate that this could be the result of divergent effects of LBPP on mean blood pressure (distending) and pulse pressure (pulsatile) responses, or alternatively, that the small magnitude (≤4 mm Hg) changes in blood pressure are not sufficient to evoke detectable changes in PWV. With respect to sympathetic outflow, cardiopulmonary baroreceptor loading has been reported to elicit smaller reflex modulations in MSNA compared with cardiopulmonary unloading 34. Whether a similar hysteresis exists with respect to the interaction of peripheral sympathetic activity on PWV is unknown, but may explain prior null findings under ganglion blockade in young participants 29, 30.…”

Section: Discussionmentioning

confidence: 98%

“…Immediately following discrete brachial blood pressure measurements, cf‐PWV was measured at minute 7 and minute 9 during both baselines and at minute 9 and 11 during each pressure stimulus. In a subset of participants, continuous measures of MSNA were also collected over the entire duration of study to provide a direct marker of peripheral sympathetic activity 34, 35. To permit all variables to return to baseline levels, participants were given at least 8 minutes of quiet rest before repeating the protocol with the alternate pressure stimulus.…”

Section: Methodsmentioning

confidence: 99%

“…To confirm that the electrode site did not alter throughout the recording periods, the neural signal was monitored both audibly and visually. Custom semiautomated LabView software (National Instruments, Austin, TX) was used to quantify MSNA burst frequency (bursts/min), and total MSNA (AU/min) 34, 35. Total MSNA was calculated as the product of mean burst area × burst frequency; as each participant acted as their own control, we did not normalize the mean burst area data.…”

Section: Methodsmentioning

confidence: 99%

“…To address prior limitations, we utilized the application of low‐level LBNP and lower body positive pressure (LBPP) shown previously to alter cardiac filling pressure and cardiopulmonary baroreflex control of peripheral sympathetic outflow directed towards skeletal muscle (muscle sympathetic nerve activity; MSNA)31, 32 without changing stroke volume or arterial pressure 32, 33, 34. Based on these data, we hypothesize that (1) in response to non‐hypotensive LBNP (−7 mm Hg), sympathetic activation will increase arterial stiffness; and (2) in response to non‐hypertensive LBPP (+7 mm Hg), sympathetic outflow will decrease in parallel with arterial stiffness.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for Pressure‐Independent Sympathetic Modulation of Central Pulse Wave Velocity

Nardone

Incognito

Millar

2018

JAHA

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BackgroundWhether the sympathetic nervous system can directly alter central aortic stiffness remains controversial, mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure.Methods and ResultsTo address this limitation, we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation. Blood pressure and carotid‐femoral aortic pulse wave velocity (cf‐PWV) were measured in 32 healthy participants (24±2 years; women: n=15) before and during 12‐minute applications of low‐level lower body negative pressure; −7 mm Hg) and lower body positive pressure; +7 mm Hg), applied in a random order. Fibular nerve microneurography was used to collect muscle sympathetic nerve activity (MSNA) in a subset (n=8) to confirm peripheral sympathetic responses. During lower body negative pressure, heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05); MSNA burst frequency (+15%; P=0.007), total MSNA (+44%; P=0.006), and cf‐PWV (∆+0.3±0.2 m/s; P<0.001) increased. In total, 28 (88%) of participants observed an increase in cf‐PWV greater than the baseline typical error of measurement. During lower body positive pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05), though blood pressure increased (P<0.05) and pulse pressure decreased (P=0.01); MSNA burst frequency (−4%; P=0.37), total MSNA (−7%; P=0.89), and cf‐PWV (∆0.0±0.2 m/s; P=0.68) were not statistically different.ConclusionsThese findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV in young participants independent of a change in distending or pulsatile blood pressure or heart rate.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evidence for Pressure‐Independent Sympathetic Modulation of Central Pulse Wave Velocity

Nardone

Incognito

Millar

2018

JAHA

Self Cite

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“…44 In heart failure, individual units within the multiunit MSNA envelope can respond independently and oppositely to different afferent baroreceptor reflex stimuli. 46 Dempsey et al 10 have suggested, on the basis of functional imaging studies, that some brain cells may be hypoxia sensitive, whereas other neuronal tissue may be selectively sensitive to arousal or sleep disruption. 17,18 We speculate, on the basis of these present findings, that both OSA and arousal can induce selective independent changes in cortical or brain stem centers governing or augmenting the firing rate of individual postganglionic sympathetic fibers thus altering such single-unit firing properties.…”

Section: Discussionmentioning

confidence: 99%

Arousal From Sleep and Sympathetic Excitation During Wakefulness

et al. 2016

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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 R 2 (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.

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Sympathetic vasoconstrictor activity before and after left ventricular assist device implantation in patients with end‐stage heart failure

Heusser

Wittkoepper

Bara

et al. 2021

European J of Heart Fail

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Aims Sympathetic overactivity, which predicts poor outcome in patients with heart failure, normalizes following cardiac transplantation. We tested the hypothesis that haemodynamic improvement following left ventricular assist device (LVAD) implantation is also associated with reductions in centrally generated sympathetic activity. Methods and results In eight patients with heart failure (two women, six men, age 44–66 years), we continuously recorded electrocardiogram, beat‐to‐beat finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) before and after implantation of the continuous‐flow LVAD devices HeartWare HVAD (n = 4) and HeartMate II (n = 2), and the non‐continuous‐flow device HeartMate 3 (n = 2). LVAD implantation increased cardiac output by 1.29 ± 0.88 L/min (P = 0.060) and mean arterial pressure by 16.2 ± 7.9 mmHg (P < 0.001), while reducing pulse pressure by 25.3 ± 9.8 mmHg (P < 0.001). LVAD implantation did not change MSNA burst frequency (−1.3 ± 7.5 bursts/min, P = 0.636), total activity (+0.62 ± 1.83 au, P = 0.369), or normalized activity (+0.63 ± 4.23, P = 0.685). MSNA burst incidence was decreased (−7.8 ± 9.3 bursts/100 heart beats, P = 0.049). However, cardiac ectopy altered MSNA bursting patterns that could be mistaken for sympatholysis. Conclusion Implantation of current design LVAD does not consistently normalize sympathetic activity in patients with end‐stage heart failure despite haemodynamic improvement.

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Paradoxical Muscle Sympathetic Reflex Activation in Human Heart Failure

Abstract: Background-Muscle sympathetic activation in heart failure with reduced ejection fraction (HFrEF)

Cited by 61 publications

References 48 publications

Evidence for Pressure‐Independent Sympathetic Modulation of Central Pulse Wave Velocity

Evidence for Pressure‐Independent Sympathetic Modulation of Central Pulse Wave Velocity

Arousal From Sleep and Sympathetic Excitation During Wakefulness

Sympathetic vasoconstrictor activity before and after left ventricular assist device implantation in patients with end‐stage heart failure

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