Digital Interventions for Social Participation in Adults with Long-term Physical Conditions: A Systematic Review.

This review aims to identify and evaluate digital interventions for social participation in the growing population of adults with long-term physical conditions. Articles were sourced from MEDLINE, EMBASE, CINAHL and PsycINFO databases using subject headings and keywords related to "social participation" and "digital technology". Studies that adopted digital technology interventions to improve social participation in adults with long-term physical conditions were included. Data on study methodology, participant and digital intervention characteristics, and findings related to social participation were extracted. The search yielded a total of 4646 articles and 14 articles met criteria for final review with five randomized controlled trials, two non-randomized clinical trials and seven one-group pretest-posttest clinical trials. Studies were organized based on the digital intervention strategy implemented to improve social participation: group support (n = 4), individual skill training or counseling (n = 6), education and support (n = 3), and mixed intervention (n = 1). The group support interventions developed a social network among participants through videoconference, app, or virtual reality platform. Three studies reported positive improvements in different aspects of social participation. Individual skill training or counseling mainly utilized phone calls to help participants cope with activity participation and interpersonal relationship issues. Only two studies demonstrated benefits for social participation. The education and support intervention, which used messages and website information to increase participants' knowledge and provide support, showed positive findings in three studies. This review suggests digital interventions for improving social participation in adults with long-term physical conditions are feasible and the effectiveness of different strategies may vary.Registration: This review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registry number: CRD42021254105).

Regulation of cerebrovascular compliance compared with forearm vascular compliance in humans: a pharmacological study.

Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (Ci) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased Ci similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular Ci (72 ± 61%) and forearm vascular Ci (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased Ci but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm.NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain.

Hybrid Functional Electrical Stimulation Improves Anaerobic Threshold in First Three Years after Spinal Cord Injury.

The purpose of the present investigation was to assess the effects of whole-body exercise on the anaerobic threshold in individuals with spinal cord injury (SCI). Maximal oxygen uptake (VO2max) and oxygen uptake at anaerobic threshold (AT) were measured before and after six months of hybrid functional electrical stimulation row training in 47 participants with SCI aged 19-63, neurological levels of injury C4-L1, American Spinal Injury Association Impairment Scale grades A-D, and time since injury at enrollment from three months to 40 years. Changes in VO2max differed with time since injury, with greater increases earlier post-injury. The early chronic group (<3 years since injury; n = 31) increased VO2max from 1.65 ± 0.54 L/min at baseline to 1.83 ± 0.66 L/min at six months (p < 0.05), while the late chronic group (>3 years since injury; n = 16) did not change (1.42 ± 0.44 at baseline to 1.47 ± 0.41 L/min at six months, p = 0.36). Consistent with VO2max changes, AT increased in the early chronic group (1.03 ± 0.31 to 1.20 ± 0.40 L/min, p < 0.05) and did not change in the late chronic group (0.99 ± 0.31 to 0.99 ± 0.26 L/min, p = 0.92). Cumulative duration of exercise training was positively correlated to change in VO2max (r = 0.475, p < 0.05) but not to change in AT. Hybrid functional electrical stimulation row training is effective for increasing aerobic capacity and anaerobic threshold in individuals with SCI; however, these fitness benefits are only significant in individuals initiating the exercise intervention within three years of injury.

Clinical Reasoning: A Young Man With Daily Episodes of Altered Awareness.

Stretch syncope is a distinct entity characterized by transient alteration in awareness (TAA) induced by neck hyperextension during stretching. Few cases of stretch syncope have been reported in the literature. Nevertheless, this is a highly relevant diagnosis as it can be easily mistaken for epilepsy for a number of reasons. These include stereotypical motor activity associated with the events, development of ictal tachycardia, and the presence of rhythmic/semirhythmic slowing on EEG in the context of transient cerebral hypoperfusion.We present the case of a young man who was referred to our comprehensive epilepsy center for frequent episodes of TAA. After careful evaluation, the episodes were initially considered to be epileptic. Given that he had negligible clinical response to antiseizure medications, he underwent an experimental protocol at a cardiovascular research laboratory that ultimately confirmed the diagnosis of stretch syncope. The present article describes an approach to the evaluation of TAA and illustrates a typical case of stretch syncope. The importance of considering stretch syncope in the differential diagnosis of TAA is exemplified. Finally, our analyses help elucidate the pathophysiology of this rare entity.

Linear Mixed Effect Models for Rehabilitation Research.

ABSTRACT: The growing emphasis on evidence-based methods in rehabilitation medicine calls for increase in the sophistication of study design and analytic methods across the discipline. To properly evaluate new treatment options, a physiatrist needs to be able to separate treatment effects from parallel changes that occur over time and variations that may be due to subject demographics. Simple t tests may not be appropriate where observations may vary randomly across different institutions participating in a multicenter trial, or the same rehabilitation course may lead to different outcomes because of various factors. In the analysis of any rehabilitation program, these random variations must be accounted for to receive accurate results. In this short review, we focus in one of the most common approaches that are appropriate to account for these variations, namely, linear mixed effect models.

The effect of heart rate variability on blood pressure is augmented in spinal cord injury and is unaltered by exercise training.

PURPOSE: To define differences in heart rate and blood pressure variability (HRV/BPV) after spinal cord injury (SCI) compared with uninjured controls, and to determine whether variabilities are impacted by whole-body exercise after SCI. METHODS: Individuals with SCI (n = 40), aged 18-40, and uninjured age/sex-matched controls (n = 22) had HRV and BPV determined during supine paced (0.25 Hz) breathing. Spectral and cross-spectral values were derived for fluctuations at low (LF 0.05-0.15 Hz) and high (HF 0.20-0.30 Hz) frequencies. Thirty-two individuals with SCI further underwent either 6 months of whole-body exercise training (n = 17) or a control intervention (n = 15). RESULTS: Individuals with SCI had injuries graded A-C in severity, neurological levels of injury C1-T10. LF and HF HRV and LF BPV were significantly lower in individuals with SCI (p = 0.008-0.002), though HF BPV was similar. The LF cross-spectrum demonstrated similar phase and gain relationships between groups. The HF phase relationship between pressure and heart rate differed markedly: individuals with SCI demonstrated a -11.7 ± 3.4° phase lag (241 ± 70 ms feedback mechanism of pressure into heart rate), whereas uninjured controls demonstrated a +21.5 ± 10.8° phase lead (443 ± 224 ms feedforward mechanism of heart rate into pressure, p = 0.007). Whole-body exercise increased mean VO2peak by 2.09 ml/kg, whereas HRV, BPV, and their cross-spectral relationships were not significantly altered relative to the control intervention after SCI. CONCLUSION: After SCI, marked frequency-specific differences exist in the relationship between heart rate and blood pressure variabilities. The high-frequency cross-spectral relationship indicates that a feedback mechanism of blood pressure into heart rate may predominate in this range.

Effect of 6-Month Exercise Training on Neurovascular Function in Spinal Cord Injury.

INTRODUCTION: Although previous data show exacerbated incidence of cognitive impairment after spinal cord injury (SCI), the physiology that underlies this postinjury cognitive decline is unknown. One potential culprit is impairment in the ability of cerebral vasculature to alter regional flow to sustain neural metabolism (i.e., "neurovascular coupling"). We hypothesized that cerebrovascular responses to a working memory task are impaired in individuals with SCI and can be improved by aerobic exercise training. METHODS: We assessed the effect of injury and 6-month full-body aerobic exercise training on the cerebral blood flow response to cognitive demand (i.e., neurovascular coupling) in 24 individuals with SCI and 16 controls. Cognitive demand was introduced in a graded fashion using a working memory task. RESULTS: Reaction time tended to be higher in individuals with SCI, especially those with high-level (≥T4) injuries, possibly due to upper motor impairments. Neurovascular coupling was graded across task difficulty (P < 0.01) and followed cognitive demand, and injury itself did not have a significant effect (group effect P = 0.99, interaction P = 0.70). Individuals with low-level injuries (

Revisiting human cerebral blood flow responses to augmented blood pressure oscillations.

KEY POINTS: Cerebral autoregulation is most effective in buffering against pressure fluctuations slower than 0.03 Hz (∼30 s). This suggests that frequency bands for characterizing cerebral autoregulation should be redefined Low cross-spectral coherence below 0.03 Hz highlights the limitations of transfer function approaches Haemodynamic changes induced by lower body pressure could not fully explain the differences in autoregulation estimated from spontaneous vs. augmented fluctuations, and thus, observations of spontaneous fluctuations should not be relied on whenever possible. ABSTRACT: There is currently little empirical basis for time scales that are considered to be most significant in cerebrovascular counter-regulation of changes in arterial pressure. Although it is well established that cerebral autoregulation behaves as a 'high-pass' filter, recommended frequency bands have been largely arbitrarily determined. To test effectiveness of cerebral autoregulation, we refined oscillatory lower body pressure (LBP) to augment resting pressure fluctuations below 0.1 Hz by a factor of two in 13 young male volunteers, and thoroughly characterized the time and frequency responses of cerebral autoregulation. We observed that despite a threefold increase in arterial pressure power <0.03 Hz with oscillatory LBP, there was no change in cerebral blood flow power, indicating near perfect counter-regulation. By contrast, in the range 0.03-0.10 Hz, both cerebral blood flow and arterial pressure power more than doubled. Our data demonstrate that cerebral autoregulation is most effective in buffering against pressure fluctuations slower than 0.03 Hz (∼30 s). This suggests that frequency bands of interest should be redefined and recording length should be increased considerably to account for this. Furthermore, low cross-spectral coherence below 0.03 Hz, even when pressure fluctuations were augmented, highlights the uncertainty in transfer function approaches and the need to either report precision or use non-linear approaches. Finally, haemodynamic changes induced by LBP could not fully explain the differences in autoregulation estimated from spontaneous vs. augmented fluctuations, and thus, observations of spontaneous fluctuations should not be relied on whenever possible.

Transcranial direct current stimulation (tDCS) and the cardiovascular responses to acute pain in humans.

OBJECTIVE: To determine if transcranial direct current stimulation (tDCS) reduces both acute pain perception and the resultant cardiovascular responses. METHODS: Data were acquired on 15 healthy subjects at rest and in response to three cold pressor tests: 0, 7, and 14 °C. Subsequently, single sessions of sham and active anodal tDCS (2.0 mA for 40 min) were delivered to the left primary motor cortex (M1). RESULTS: Perceived pain was reduced only after active tDCS with the 14 °C cold pressor test. This was accompanied by tendency for lesser increases in heart rate (~2 beats/min, p=0.09) and blood pressure (~3 mmHg, p=0.06). The effect size of tDCS on peak heart rate and blood pressure responses at 14 °C was 0.47 and 0.54, respectively. On the other hand, baseline heart rate, blood pressure, leg blood flow, and leg vascular resistance were unaffected by tDCS. No other responses were affected. CONCLUSIONS: Our results demonstrate that M1 anodal tDCS has no effect on basal hemodynamics or cardiovascular autonomic outflow and has only modest effects on the responses to acute pain in healthy humans. SIGNIFICANCE: Application of tDCS shifts the pain perception threshold in healthy individuals but does not significantly modulate efferent cardiovascular control at rest or in response to pain.

Assessing cerebral autoregulation via oscillatory lower body negative pressure and projection pursuit regression.

The process by which cerebral perfusion is maintained constant over a wide range of systemic pressures is known as "cerebral autoregulation." Effective dampening of flow against pressure changes occurs over periods as short as ~15 sec and becomes progressively greater over longer time periods. Thus, slower changes in blood pressure are effectively blunted and faster changes or fluctuations pass through to cerebral blood flow relatively unaffected. The primary difficulty in characterizing the frequency dependence of cerebral autoregulation is the lack of prominent spontaneous fluctuations in arterial pressure around the frequencies of interest (less than ~0.07 Hz or ~15 sec). Oscillatory lower body negative pressure (OLBNP) can be employed to generate oscillations in central venous return that result in arterial pressure fluctuations at the frequency of OLBNP. Moreover, Projection Pursuit Regression (PPR) provides a nonparametric method to characterize nonlinear relations inherent in the system without a priori assumptions and reveals the characteristic non-linearity of cerebral autoregulation. OLBNP generates larger fluctuations in arterial pressure as the frequency of negative pressure oscillations become slower; however, fluctuations in cerebral blood flow become progressively lesser. Hence, the PPR shows an increasingly more prominent autoregulatory region at OLBNP frequencies of 0.05 Hz and below (20 sec cycles). The goal of this approach it to allow laboratory-based determination of the characteristic nonlinear relationship between pressure and cerebral flow and could provide unique insight to integrated cerebrovascular control as well as to physiological alterations underlying impaired cerebral autoregulation (e.g., after traumatic brain injury, stroke, etc.).

Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation.

BACKGROUND AND PURPOSE: Prior work aimed at improving our understanding of human cerebral autoregulation has explored individual physiological mechanisms of autoregulation in isolation, but none has attempted to consolidate the individual roles of these mechanisms into a comprehensive model of the overall cerebral pressure-flow relationship. METHODS: We retrospectively analyzed this relationship before and after pharmacological blockade of α-adrenergic-, muscarinic-, and calcium channel-mediated mechanisms in 43 healthy volunteers to determine the relative contributions of the sympathetic, cholinergic, and myogenic controllers to cerebral autoregulation. Projection pursuit regression was used to assess the effect of pharmacological blockade on the cerebral pressure-flow relationship. Subsequently, ANCOVA decomposition was used to determine the cumulative effect of these 3 mechanisms on cerebral autoregulation and whether they can fully explain it. RESULTS: Sympathetic, cholinergic, and myogenic mechanisms together accounted for 62% of the cerebral pressure-flow relationship (P<0.05), with significant and distinct contributions from each of the 3 effectors. ANCOVA decomposition demonstrated that myogenic effectors were the largest determinant of the cerebral pressure-flow relationship, but their effect was outside of the autoregulatory region where neurogenic control appeared prepotent. CONCLUSIONS: Our results suggest that myogenic effects occur outside the active region of autoregulation, whereas neurogenic influences are largely responsible for cerebral blood flow control within it. However, our model of cerebral autoregulation left 38% of the cerebral pressure-flow relationship unexplained, suggesting that there are other physiological mechanisms that contribute to cerebral autoregulation.

The role of myogenic mechanisms in human cerebrovascular regulation.

Although myogenic mechanisms have been hypothesized to play a role in cerebrovascular regulation, previous data from both animals and humans have not provided an unequivocal answer. However, cerebral autoregulation is explicitly non-linear and most prior work relied on simple linear approaches for assessment, potentially missing important changes in autoregulatory characteristics. Therefore, we examined cerebral blood flow responses to augmented arterial pressure oscillations with and without calcium channel blockade (nicardipine) during blood pressure fluctuations (oscillatory lower body negative pressure, OLBNP) across a range of frequencies in 16 healthy subjects. Autoregulation was characterized via a robust non-linear method (projection pursuit regression, PPR). Blockade resulted in significant tachycardia, a modest but significant elevation in mean arterial pressure, and reductions in mean cerebral blood flow and end-tidal CO2 during OLBNP. The reductions in flow were directly related to the reductions in CO2 (r = 0.57). While linear cross-spectral analysis showed that the relationship between pressure-flow fluctuations was preserved after blockade, PPR showed that blockade significantly altered the non-linearity between pressure and flow, particularly at the slowest fluctuations. At 0.03 Hz, blockade reduced the range of pressure fluctuations that can be buffered (7.5 ± 1.0 vs. 3.7 ± 0.8 mmHg) while increasing the autoregulatory slope (0.10 ± 0.05 vs. 0.24 ± 0.08 cm s(-1) mmHg(-1)). Furthermore, the same rate of change in pressure elicited a change in flow more than twice as large as at baseline. Thus, our results show that myogenic mechanisms play a significant role in cerebrovascular regulation but this may not be appreciated without adequately characterizing the non-linearities inherent in cerebrovascular regulation.

Characterizing sympathetic neurovascular transduction in humans.

Despite its critical role for cardiovascular homeostasis in humans, only a few studies have directly probed the transduction of sympathetic nerve activity to regional vascular responses--sympathetic neurovascular transduction. Those that have variably relied on either vascular resistance or vascular conductance to quantify the responses. However, it remains unclear which approach would better reflect the physiology. We assessed the utility of both of these as well as an alternative approach in 21 healthy men. We recorded arterial pressure (Finapres), peroneal sympathetic nerve activity (microneurography), and popliteal blood flow (Doppler) during isometric handgrip exercise to fatigue. We quantified and compared transduction via the relation of sympathetic activity to resistance and to conductance and via an adaptation of Poiseuille's relation including pressure, sympathetic activity, and flow. The average relationship between sympathetic activity and resistance (or conductance) was good when assessed over 30-second averages (mean R(2) = 0.49±0.07) but lesser when incorporating beat-by-beat time lags (R(2) = 0.37±0.06). However, in a third of the subjects, these relations provided relatively weak estimates (R(2)<0.33). In contrast, the Poiseuille relation reflected vascular responses more accurately (R(2) = 0.77±0.03, >0.50 in 20 of 21 individuals), and provided reproducible estimates of transduction. The gain derived from the relation of resistance (but not conductance) was inversely related to transduction (R(2) = 0.37, p<0.05), but with a proportional bias. Thus, vascular resistance and conductance may not always be reliable surrogates for regional sympathetic neurovascular transduction, and assessment from a Poiseuille relation between pressure, sympathetic nerve activity, and flow may provide a better foundation to further explore differences in transduction in humans.

Cholinergic control of the cerebral vasculature in humans.

Despite growing evidence of autonomic nervous system involvement in the regulation of cerebral blood flow, the specific contribution of cholinergic vasodilatation to cerebral autoregulation remains unknown. We examined cerebral and forearm blood flow responses to augmented arterial pressure oscillations with and without cholinergic blockade. Oscillatory lower body negative pressure was applied at six frequencies from 0.03 to 0.08 Hz in nine healthy subjects with and without cholinergic blockade via glycopyrrolate. Cholinergic blockade increased cross-spectral coherence between arterial pressure and cerebral flow at all frequencies except 0.03 Hz and increased the transfer function gain at frequencies above 0.05 Hz. In contrast, gain between pressure and forearm flow increased only at frequencies below 0.06 Hz. These data demonstrate that the cholinergic system plays an active and unique role in cerebral autoregulation. The frequency region and magnitude of effect is very similar to what has been seen with sympathetic blockade, indicating a possible balance between the two reflexes to most effectively respond to rising and falling pressure. These findings might have implications for the role of dysfunction in autonomic control of the vasculature in cerebrovascular disease states.

Sympathetic control of the cerebral vasculature in humans.

BACKGROUND AND PURPOSE: The role of the sympathetic nervous system in cerebral autoregulation remains poorly characterized. We examined cerebral blood flow responses to augmented arterial pressure oscillations with and without sympathetic blockade and compared them with responses in the forearm circulation. METHODS: An oscillatory lower body negative pressure of 40 mm Hg was used at 6 frequencies from 0.03 to 0.08 Hz in 11 healthy subjects with and without alpha-adrenergic blockade by phentolamine. RESULTS: Sympathetic blockade resulted in unchanged mean pressure and cerebral flow. The transfer function relationship to arterial pressure at frequencies >0.05 Hz was significantly increased in both the cerebral and brachial circulations, but the coherence of the relation remained weak at the lowest frequencies in the cerebral circulation. CONCLUSIONS: Our data demonstrate a strong, frequency-dependent role for sympathetic regulation of blood flow in both cerebral and brachial circulations. However, marked differences in the response to blockade suggest the control of the cerebral circulation at longer time scales is characterized by important nonlinearities and relies on regulatory mechanisms other than the sympathetic system.

Spectral indices of human cerebral blood flow control: responses to augmented blood pressure oscillations.

We set out to fully examine the frequency domain relationship between arterial pressure and cerebral blood flow. Oscillatory lower body negative pressure (OLBNP) was used to create consistent blood pressure oscillations of varying frequency and amplitude to rigorously test for a frequency- and/or amplitude-dependent relationship between arterial pressure and cerebral flow. We also examined the predictions from OLBNP data for the cerebral flow response to the stepwise drop in pressure subsequent to deflation of ischaemic thigh cuffs. We measured spectral powers, cross-spectral coherence, and transfer function gains and phases in arterial pressure and cerebral flow during three amplitudes (0, 20, and 40 mmHg) and three frequencies (0.10, 0.05, and 0.03 Hz) of OLBNP in nine healthy young volunteers. Pressure fluctuations were directly related to OLBNP amplitude and inversely to OLBNP frequency. Although cerebral flow oscillations were increased, they did not demonstrate the same frequency dependence seen in pressure oscillations. The overall pattern of the pressure-flow relation was of decreasing coherence and gain and increasing phase with decreasing frequency, characteristic of a high-pass filter. Coherence between pressure and flow was increased at all frequencies by OLBNP, but was still significantly lower at frequencies below 0.07 Hz despite the augmented pressure input. In addition, predictions of thigh cuff data from spectral estimates were extremely inconsistent and highly variable, suggesting that cerebral autoregulation is a frequency-dependent mechanism that may not be fully characterized by linear methods.

Mental stress response, arterial stiffness, and baroreflex sensitivity in healthy aging.

This study examined the relationship of pressor responses during mental stress to arterial stiffness and baroreflex sensitivity. Hemodynamic responses of 24 healthy individuals (51-86 years old) to two mental stress tasks (math and speech) were compared with common carotid artery mechanical stiffness and autonomic nervous system regulation of blood pressure as measured by using the modified Oxford technique. At the ages studied, no effect of age on stress task responsiveness, carotid stiffness, or baroreflex sensitivity was observed. Carotid stiffness and baroreflex sensitivity demonstrated a strong inverse relation. Change in heart rate during the speech task was correlated with arterial stiffness, and the increase in mean arterial pressure was associated with carotid stiffness and was inversely correlated to baroreflex sensitivity. These associations suggest that acute hemodynamic reactions to mental stress among healthy adults are determined, in part, by structural properties of arterial vessels and sensitivity of arterial baroreflex. These observations may provide a mechanistic link between the physiology of cardiovascular reactivity to stress and risk of cardiovascular events in middle-aged and older individuals.

Automated quantification of sympathetic beat-by-beat activity, independent of signal quality.

Sympathetic nerve activity (SNA) can provide critical information on cardiovascular regulation; however, in a typical laboratory setting, adequate recordings require assiduous effort, and otherwise high-quality recordings may be clouded by frequent baseline shifts, noise spikes, and muscle twitches. Visually analyzing this type of signal can be a tedious and subjective evaluation, whereas objective analysis through signal averaging is impossible. We propose a new automated technique to identify bursts through objective detection criteria, eliminating artifacts and preserving a beat-by-beat SNA signal for a variety of subsequent analyses. The technique was evaluated during both steady-state conditions (17 subjects) and dynamic changes with rapid vasoactive drug infusion (14 recordings from 5 subjects) on SNA signals of widely varied quality. Automated measures of SNA were highly correlated to visual measures of steady-state activity (r = 0.903, P < 0.001), dynamic relation measures (r = 0.987, P < 0.001), and measures of burst-by-burst variability (r = 0.929, P < 0.001). This automated sympathetic neurogram analysis provides a viable alternative to tedious and subjective visual analyses while maximizing the usability of noisy nerve tracings.

Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women.

BACKGROUND: Menopausal estrogen loss has been associated with increased cardiovascular disease in postmenopausal women. However, the link between estrogen and cardiovascular disease remains unclear. Some data suggest estrogen mediates its effect through changes in arterial pressure and its regulation. However, the data available in older women are equivocal regarding estrogen's ability to reduce resting arterial pressure or to improve its regulation. METHODS AND RESULTS: We studied 11 healthy, postmenopausal women before and after 6 months of estrogen administration. Arterial pressure was measured by brachial auscultation and finger photoplethysmography. Vascular sympathetic nerve activity was measured in the peroneal nerve by microneurography, and the slope of the relations between changes in heart period, sympathetic activity, and arterial pressure caused by bolus infusions of nitroprusside and phenylephrine were used as an index of baroreflex gain. Estrogen therapy did not change systolic pressure (128+/-2 versus 123+/-2 mm Hg) or cardiac-vagal baroreflex gain (6.6+/-0.9 versus 6.7+/-0.7 ms/mm Hg). However, vascular sympathetic baroreflex gain was increased (-4.6+/-0.6 versus -7.4+/-1.0 arbitrary integrated units/mm Hg; P=0.02). CONCLUSION: These findings suggest long-term estrogen replacement therapy has effects on cardiovascular regulation that may not be reflected in resting arterial pressures.