Oscillatory Pattern of Sympathetic Nerve Bursts Is Associated With Baroreflex Function in Heart Failure Patients With Reduced Ejection Fraction

Sympathetic hyperactivation and baroreflex dysfunction are hallmarks of heart failure with reduced ejection fraction (HFrEF). However, it is unknown whether the progressive loss of phasic activity of sympathetic nerve bursts is associated with baroreflex dysfunction in HFrEF patients. Therefore, we investigated the association between the oscillatory pattern of muscle sympathetic nerve activity (LFMSNA/HFMSNA) and the gain and coupling of the sympathetic baroreflex function in HFrEF patients. In a sample of 139 HFrEF patients, two groups were selected according to the level of LFMSNA/HFMSNA index: (1) Lower LFMSNA/HFMSNA (lower terciles, n = 46, aged 53 ± 1 y) and (2) Higher LFMSNA/HFMSNA (upper terciles, n = 47, aged 52 ± 2 y). Heart rate (ECG), arterial pressure (oscillometric method), and muscle sympathetic nerve activity (microneurography) were recorded for 10 min in patients while resting. Spectral analysis of muscle sympathetic nerve activity was conducted to assess the LFMSNA/HFMSNA, and cross-spectral analysis between diastolic arterial pressure, and muscle sympathetic nerve activity was conducted to assess the sympathetic baroreflex function. HFrEF patients with lower LFMSNA/HFMSNA had reduced left ventricular ejection fraction (26 ± 1 vs. 29 ± 1%, P = 0.03), gain (0.15 ± 0.03 vs. 0.30 ± 0.04 a.u./mmHg, P < 0.001) and coupling of sympathetic baroreflex function (0.26 ± 0.03 vs. 0.56 ± 0.04%, P < 0.001) and increased muscle sympathetic nerve activity (48 ± 2 vs. 41 ± 2 bursts/min, P < 0.01) and heart rate (71 ± 2 vs. 61 ± 2 bpm, P < 0.001) compared with HFrEF patients with higher LFMSNA/HFMSNA. Further analysis showed an association between the LFMSNA/HFMSNA with coupling of sympathetic baroreflex function (R = 0.56, P < 0.001) and left ventricular ejection fraction (R = 0.23, P = 0.02). In conclusion, there is a direct association between LFMSNA/HFMSNA and sympathetic baroreflex function and muscle sympathetic nerve activity in HFrEF patients. This finding has clinical implications, because left ventricular ejection fraction is less in the HFrEF patients with lower LFMSNA/HFMSNA.

Evening Binge Alcohol Disrupts Cardiovagal Tone and Baroreflex Function During Polysomnographic Sleep

Study Objectives Binge alcohol consumption is associated with increased cardiovascular risk. The effects of evening binge alcohol consumption (i.e., 4-5 beverages within two hours) on the vagal components of HRV and cardiovagal baroreflex sensitivity (cvBRS) during sleep remain largely equivocal. The present study examined the effects of evening binge alcohol consumption on nocturnal cardiac vagal tone and baroreflex sensitivity during stage N2, slow wave (SWS), and rapid eye movement (REM) sleep. We hypothesized that evening binge drinking would reduce HRV and cvBRS in each sleep stage. Methods Following a familiarization night within the laboratory, twenty-three participants were examined following a night of binge alcohol consumption and a fluid control (randomized, crossover design). A quality nocturnal beat-to-beat blood pressure signal was obtained in both conditions in 16 participants (7 men, 9 women; 25±1 years). Results Binge drinking reduced both the high frequency (HF) and time-domain components (i.e., pNN50 and RMSSD) of HRV in stage N2 sleep, SWS, and REM. In addition, cvBRS up-up (vagal activation) was reduced following binge alcohol consumption in stage N2 (21±3 vs. 15±3 ms/mmHg, P=0.035) and REM (15[11-28] vs. 11[9-18] ms/mmHg, P=0.009). Binge alcohol consumption reduced cvBRS down-down (vagal withdrawal) in stage N2 (23±2 vs. 14±2 ms/mmHg, P<0.001), SWS (20[14-30] vs. 14[9-17] ms/mmHg, P=0.022), and REM (14[11-24] vs. 10[7-15] ms/mmHg, P=0.006). Conclusions Evening binge alcohol consumption disrupts cardiac vagal tone and baroreflex function during nearly all sleep stages. These findings provide mechanistic insight into the potential role of binge drinking and alcohol abuse on cardiovascular risk.

Baroreflex dysfunction in Parkinson's disease: Integration of central and peripheral mechanisms

The incidence of Parkinson's disease (PD) is increasing worldwide. Although the PD hallmark is the motor impairments, non-motor dysfunctions are now becoming more recognized. Recently, studies have suggested that baroreflex dysfunction is one of the underlying mechanisms of cardiovascular dysregulation observed in patients with PD. However, the large body of literature on baroreflex function in PD is unclear. The baroreflex system plays a major role in the autonomic, and ultimately blood pressure and heart rate, adjustments that accompany acute cardiovascular stressors on a daily basis. Therefore, impaired baroreflex function (i.e., decreased sensitivity or gain) can lead to altered neural cardiovascular responses. Since PD affects parasympathetic and sympathetic branches of the autonomic nervous system and both are orchestrated by the baroreflex system, the understanding of this crucial mechanism in PD is necessary. In the present review, we summarize the potential altered central and peripheral mechanisms affecting the feedback controlled loops that comprise the reflex arc in patients with PD. Major factors including arterial stiffness, reduced number of C1 and activation of non-C1 neurons, presence of centrally α-synuclein aggregation, cardiac sympathetic denervation, attenuated muscle sympathetic nerve activity, and lower norepinephrine release could compromise baroreflex function in PD. Results from patients with PD and from animal models of PD will provide the reader a clearer picture on baroreflex function in this clinical condition. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this research area.

Intranasal Oxytocin has sympathoexcitatory effects on vascular tone in healthy males

Objective: Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides like oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. Methods: In a balanced, double-blind cross-over design oxytocin or placebo was administered intranasally to 12 lean healthy males (age 25±4 years). MSNA was assessed microneurographically before (pre), 30-45 (post-I) and 105-120 minutes (post-II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5h fasting period. Results: After oxytocin, resting MSNA (burst rate and total activity) showed significant net-increases from pre to post-II compared to placebo (∆-increase: +4.3±1.2 (oxytocin) vs. +2.2±1.4 burst/min (placebo), ANOVA p<0.05; total activity 184±11.5% (oxytocin) vs. 121±14.3% (placebo), ANOVA; p=0.01). This was combined with a small but significant net-increase in resting diastolic BP, while systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Conclusion: Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex setpoint at centers superordinate to the mere baroreflex-feedback-loop.

Baroreflex function in Parkinson's disease: insights from the modified-Oxford technique

Attenuated baroreflex gain may contribute to adverse cardiovascular outcomes, including orthostatic intolerance symptoms typically observed in patients with Parkinson's disease. We found that the baroreflex gain (assessed by the modified-Oxford technique) is attenuated and accompanied by an increased operating range in patients with Parkinson's disease. These findings highlight that cardiovascular perturbations are required to detect baroreflex impairments and that spontaneous indices do not reveal cardiovagal-baroreflex dysfunction in a middle-aged group of patients with Parkinson's disease.