Cardiorespiratory Effects of Yogic Versus Slow Breathing in Individuals with a Spinal Cord Injury: An Exploratory Cohort Study.

Background: An intricate physiological and pathophysiological connection exists between the heart and lungs, which is especially important in individuals with spinal cord injury (SCI). While an exercise intervention may seem the best approach to leverage this relationship, the prior work has shown that, despite numerous health benefits, regular exercise training does not improve cardiorespiratory control in individuals with SCI. Breath training presents an alternative intervention that is uniquely accessible, with yogic breathing directly engaging linked fluctuations in respiration and cardiovascular control. In addition, there is evidence across a range of populations that regular yogic breathing reduces cardiovascular disease risk. It is possible that the chronic decrease in breathing frequency associated with regular yogic breathing, rather than the specific yogic breathing techniques themselves, is the primary contributor to the observed risk reduction. Methods: Therefore, in 12 individuals with traumatic SCI from C4 to T8, the authors compared Unpaced and conventional 0.083 Hz (Slow) paced breathing with various yogic breathing techniques including: (1) inspiratory-expiratory breath holds (i.e., Kumbhaka or "Box Breathing"), (2) extended exhalation (1:2 duty cycle), and (3) expiratory resistance via throat constriction (i.e., Ujjayi). Beat-to-beat heart rate and blood pressure were measured as well as end-tidal CO2 and O2 saturation were measured. Statistical analysis was performed using a one-way repeated-measures analysis of variance with post hoc pairwise t tests corrected for multiple comparisons. Results: As expected, all slow breathing patterns markedly increased respiratory sinus arrhythmia (RSA) compared with Unpaced in all (n = 12) individuals. More importantly, Ujjayi breathing appeared to improve ventilatory efficiency over Unpaced breathing in individuals with SCI by increasing O2 saturation (97.6% vs. 96.1%; p = 0.042) and tended to decrease end-tidal CO2 (32 mmHg vs. 35 mmHg; p = 0.08). While other slow breathing patterns demonstrated similar effects, only Ujjayi improved RSA while increasing heart rate and improving ventilatory efficiency. Conclusions: Hence, slow breathing per se can result in important cardiorespiratory changes, but the yogic breathing practice of Ujjayi, with glottic throat resistance, may hold the greatest promise for improving cardiorespiratory control in individuals with SCI (CTR ID No. NCT05480618).

Nitric oxide-mediated vasodilation in human bone.

OBJECTIVE: Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone. METHODS: In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg. RESULTS: LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 µM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 µM) at 10 min (p = .01). CONCLUSIONS: In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.

Transcutaneous spinal cord stimulation and its impact on cardiovascular autonomic regulation after spinal cord injury.

Individuals with spinal cord injury (SCI) have significant dysfunction in cardiovascular autonomic regulation. Although recent findings postulate that spinal cord stimulation improves autonomic regulation, limited scope of past methods have tested only above level sympathetic activation, leaving significant uncertainty. To identify whether transcutaneous spinal cord stimulation improves cardiovascular autonomic regulation, two pairs of well-matched individuals with and without high thoracic, complete SCI were recruited. Baseline autonomic regulation was characterized with multiple tests of sympathoinhibition and above/below injury level sympathoexcitation. At three subsequent visits, testing was repeated with the addition submotor threshold transcutaneous spinal cord stimulation at three previously advocated frequencies. Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. As expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared with baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in cardiovascular autonomic regulation. Collectively, transcutaneous spinal cord stimulation demonstrates no improvements in autonomic regulation after SCI, and instead likely generates tonic sympathoexcitation which may lower the threshold for dangerous autonomic dysreflexia.NEW & NOTEWORTHY Spinal cord stimulation increases blood pressure after spinal cord injury, though it is unclear if this restores natural autonomic regulation or induces a potentially dangerous pathological reflex. We performed comprehensive autonomic testing batteries, with and without transcutaneous spinal cord stimulation at multiple frequencies. Across 96 independent tests, stimulation did not change uninjured control responses, though all frequencies facilitated pathological reflexes without improved autonomic regulation for those with spinal cord injuries.

The Impact of Transcutaneous Spinal Cord Stimulation on Autonomic Regulation after Spinal Cord Injury: A randomized crossover trial.

Importance: Individuals with spinal cord injury (SCI) have significant autonomic nervous system dysfunction. However, despite recent findings postulated to support that spinal cord stimulation improves dynamic autonomic regulation, limited scope of previous testing means the true effects remain unknown. Objective: To determine whether transcutaneous spinal cord stimulation improves dynamic autonomic regulation after SCI. Design: Single-blinded, randomized crossover trial with matched cohorts. Setting: Academic autonomic physiology laboratory. Participants: Two pairs of well-matched individuals with and without high-thoracic, complete SCI. Interventions: Sub-motor threshold transcutaneous spinal cord stimulation delivered at T10-T11 using 120Hz, 30Hz, and 30Hz with 5kHz carrier frequency at separate autonomic testing sessions. Main Outcomes and Measures: Baseline autonomic regulation was characterized with tests of above injury level sympathoexcitation (Valsalva's maneuver), sympathoinhibition (progressive doses of bolus intravenous phenylephrine), and below level sympathoexcitation (foot cold pressor test). At three subsequent visits, this testing battery was repeated with the addition of spinal cord stimulation at each frequency. Changes in autonomic regulation for each frequency were then analyzed relative to baseline testing for each individual and within matched cohorts. Results: Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. Contrasting this, and as expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared to baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in autonomic regulation. Conclusions and Relevance: Transcutaneous spinal cord stimulation does not improve autonomic regulation after SCI, and instead likely generates tonic, frequency-dependent sympathoexcitation which may lower the threshold for autonomic dysreflexia.

Dynamic effects of cholinergic blockade upon cerebral blood flow autoregulation in healthy adults.

Background: Cerebral flow autoregulation (CFA) is a homeostatic mechanism critical for survival. The autonomic nervous system (ANS) plays a key role in maintaining proper CFA function. More quantitative studies of how the ANS influences CFA are desirable. Objective: To discover and quantify the dynamic effects of cholinergic blockade upon CFA in response to changes of arterial blood pressure and blood CO2 tension in healthy adults. Methods: We analyzed time-series data of spontaneous beat-to-beat mean arterial blood pressure (ABP) and cerebral blood flow velocity in the middle cerebral arteries (CFV), as well as breath-to-breath end-tidal CO2 (CO2), collected in 9 adults before and after cholinergic blockade, in order to obtain subject-specific predictive input-output models of the dynamic effects of changes in ABP and CO2 (inputs) upon CFV (output). These models are defined in convolutional form using "kernel" functions (or, equivalently, Transfer Functions in the frequency domain) that are estimated via the robust method of Laguerre expansions. Results: Cholinergic blockade caused statistically significant changes in the obtained kernel estimates (and the corresponding Transfer Functions) that define the linear dynamics of the ABP-to-CFV and CO2-to-CFV causal relations. The kernel changes due to cholinergic blockade reflect the effects of the cholinergic mechanism and exhibited, in the frequency domain, resonant peaks at 0.22 Hz and 0.06 Hz for the ABP-to-CFV and CO2-to-CFV dynamics, respectively. Conclusion: Quantitative estimates of the dynamics of the cholinergic component in CFA are found as average changes of the ABP-to-CFV and CO2-to-CFV kernels, and corresponding Transfer Functions, before and after cholinergic blockade.

Methodologic implications for rehabilitation research: Differences in heart rate variability introduced by respiration.

BACKGROUND: Heart rate variability is a measure of autonomic activity that is growing in popularity as a research outcome. However, despite its increased use, the known effects of respiration on heart rate variability measures are rarely accounted for in rehabilitation medicine research, leading to potential misinterpretation. OBJECTIVE: To describe the effect that unpaced and paced breathing introduces to heart rate variability measures in a rehabilitation medicine relevant example of individuals with spinal cord injury. DESIGN: Cross-sectional comparison of heart rate variability during unpaced and paced breathing (0.25 Hz, 15 breaths per minute) within the same individuals during the same lab session. SETTING: Academic autonomic physiology laboratory. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mean low frequency (LF) and high frequency (HF) heart rate variability power, percentage of total power derived from the LF spectrum, LF:HF ratio. RESULTS: Fifty-nine individuals with spinal cord injury completed laboratory assessments using standardized protocols (NCT02139436). In repeated measures within individuals, mean LF power was significantly higher in unpaced breathing compared to paced breathing (1292 vs. 573 ms2 , p < .001). A Bland-Altman plot demonstrated significant positive proportional bias for LF power when comparing unpaced and paced breathing conditions (R2  = 0.39). Mean HF power was similar between unpaced and paced breathing conditions, although there were wide positive and negative differences between measures, leading to notable uncertainty when respiratory confounders were not accounted for. The percentages of total power derived from the LF spectrum and the mean LF:HF ratio were both significantly higher for unpaced breathing compared to paced breathing (64 vs. 42%, p < .001; and 3.2 vs. 1.1, p < .001, respectively). CONCLUSION: Respiration has a significant effect on heart rate variability following spinal cord injury, and not accounting for this has serious consequences for accurate interpretation of unpaced data. Future studies of heart rate variability in rehabilitation medicine should accordingly consider paced breathing.

Association of Hemodynamic and Cerebrovascular Responses to Exercise With Symptom Severity in Adolescents and Young Adults With Concussion.

BACKGROUND AND OBJECTIVES: Aerobic exercise has become a useful method to assist with postconcussion management. Exercise can exacerbate concussion symptoms even when symptoms are not apparent at rest. Few studies have examined the reasons for symptom exacerbation during exercise following a concussion. We had 2 primary objectives: (1) to delineate cardiopulmonary and cerebrovascular responses to exercise in adolescents and young adults with a concussion and healthy controls and (2) to determine the association between cerebrovascular responses and symptom burden. METHODS: We recruited participants with a recent concussion from a sport concussion clinic between September 1, 2018, and February 22, 2020. They were included if their concussion occurred <3 weeks before initial testing and if they were symptomatic at rest. Participants were excluded if they sustained a concussion in the past year (excluding index injury), reported history of neurologic disorders, or were using medications/devices that may alter neurologic function. Participants completed a progressive, symptom-limited, submaximal exercise protocol on a stationary bicycle. We assessed heart rate, blood pressure, fraction of end tidal CO2 (FETCO2), and middle cerebral artery blood flow velocity (CBF) and cerebrovascular function (vasoactivity and autoregulation) at seated rest and during exercise. RESULTS: We conducted 107 exercise tests (40 concussed, 37 healthy participants initially; 30 concussed at follow-up). Concussed participants were tested initially (mean 17.6 ± 2.2 [SD] years of age; 55% female; mean 12.5 ± 4.7 days postconcussion) and again 8 weeks later (mean 73.3 ± 9.5 days postconcussion). Control participants (mean 18.3 ± 2.4 years; 62% female) were tested once. FETCO2 increased throughout the exercise protocol as heart rate increased, reached a plateau, and declined at higher exercise intensities. CO2 explained >25% of the variation in resting CBF (R 2 > 0.25; p < 0.01) in most (73% individuals). Within the concussion group, resting symptom severity and the heart rate at which FETCO2 reached a plateau explained ∼2/3s of variation in exercise-induced symptom exacerbation (R 2 = 0.65; FETCO2 ß = -1.210 ± 0.517 [SE], p < 0.05). There was a moderate, statistically significant relationship between cerebrovascular responses to CO2 at rest (cerebral vasoactivity) and cerebrovascular responses to exercise-induced changes in FETCO2 (R 2 = 0.13, p = 0.01). DISCUSSION: The arterial CO2 response and symptom exacerbation relationship during postconcussion aerobic exercise may be mediated by increased sensitivity of cerebral vasculature to exercise-related increase in CO2.

Executive dysfunction after multiple concussions is not related to cerebrovascular dysfunction.

Objective.We investigated the relation between prior concussion history and working memory (WM), self-reported cognitive symptom burden, and cerebrovascular function in adolescents and young adults (14-21 years old).Approach.We recruited 59 participants, 34 clinically diagnosed with a sports-related concussion and 25 controls. Concussed subjects were studied at baseline (within 28 days of their injury) and eight weeks after, while control subjects only had one assessment. We assessed WM (n-back task up to four-back), and neurovascular coupling (cerebrovascular responses at middle cerebral artery duringn-back tasks) using a transcranial Doppler ultrasonograph.Main results.There was no significant difference in WM between controls and concussed participants (p = 0.402). However, WM capacity was lower in those who had sustained ≥3 concussions (7.1% with WM capacity of four) compared to those with their first ever concussion (33.3%) and controls (28.0%, overallp = 0.025). At the sub-acute point (n = 24), self-reported cognitive symptom burden was mostly resolved in all but two participants. Despite the resolution of symptoms, WM performance was not different eight weeks post injury (p = 0.706). Neurovascular coupling was not different between controls and concussed participants regardless of prior concussion history.Significance. Up to 20% of concussed individuals experience covert sequelae lasting beyond the resolution of self-reported overt symptoms. How a prior history of concussion impacts the potential for sequelae is not well established, and the underlying mechanisms are unknown. Despite no alterations in neurovascular coupling, a history of prior concussion was associated with significant deficits in WM capacity, and lasted beyond self-reported cognitive symptom resolution.

Cerebrovascular Neuroprotection after Acute Concussion in Adolescents.

OBJECTIVE: To assess acute cerebrovascular function in concussed adolescents (14-21 years of age), whether it is related to resting cerebral hemodynamics, and whether it recovers chronically. METHODS: Cerebral vasoreactivity and autoregulation, based on middle cerebral artery blood flow velocity, was assessed in 28 concussed participants (≤14 days of injury) and 29 matched controls. The participants in the concussion group returned for an 8-week follow-up assessment. Over the course of those 8-weeks, participants recorded aerobic exercise frequency and duration. RESULTS: Between groups, demographic, clinical, and hemodynamic variables were not significantly different. Vasoreactivity was significantly higher in the concussed group (p = 0.02). Within the concussed group, 60% of the variability in resting cerebral blood flow velocity was explained by vasoreactivity and two components of autoregulation - falling slope and effectiveness of autoregulation (adjusted R2  = 0.60, p < 0.001). Moreover, lower mean arterial pressure, lower responses to increases in arterial pressure, and lower vasoreactivity were significantly associated with larger symptom burden (adjusted R2  = 0.72, p < 0.01). By the 8-week timepoint, symptom burden, but not vasoreactivity, improved in all but four concussed participants (p < 0.01). 8-week change in vasoreactivity was positively associated with aerobic exercise volume (adjusted R2  = 0.19, p = 0.02). INTERPRETATION: Concussion resulted in changes in cerebrovascular regulatory mechanisms, which in turn explained the variability in resting cerebral blood flow velocity and acute symptom burden. Furthermore, these alterations persisted chronically despite symptom resolution, but was positively modified by aerobic exercise volume. These findings provide a mechanistic framework for further investigation into underlying cerebrovascular related symptomatology. ANN NEUROL 2021;90:43-51.

High-intensity, whole-body exercise improves blood pressure control in individuals with spinal cord injury: A prospective randomized controlled trial.

Blood pressure regulation following spinal cord injury (SCI) is often compromised due to impaired vascular sympathetic control, leading to increased reliance on cardiovagal baroreflex sensitivity to maintain pressure. Whole-body exercise improves cardiovagal baroreflex sensitivity in uninjured individuals, though has not been explored in those with SCI. Our objective was to determine changes in cardiovagal baroreflex sensitivity following 6 months of high-intensity, whole-body exercise in individuals with SCI compared to lower-intensity, arms only exercise, or waitlist. This randomized controlled trial recruited individuals with SCI aged 18-40 years old. Sixty-one individuals were randomized, with 38 completing at least one cardiovagal baroreflex sensitivity assessment. Whole-body exercise was performed with hybrid functional electrical stimulation rowing prescribed as two to three times per week, for 30-60 minutes with a target heart rate of >75% of maximum. The arms only exercise group performed upper body rowing exercise with the same prescription as whole-body exercise. Waitlist controls were not enrolled in any explicit training regimen. After 6 months, those in arms only exercise or waitlist crossed over to whole-body exercise. Cardiovagal baroreflex sensitivity was assessed via the neck suction technique at baseline and at three-month intervals thereafter. Intention to treat analysis with a structured equation model demonstrated no significant effect of waitlist control or arms only exercise on cardiovagal baroreflex sensitivity. Whole-body exercise significantly improved cardiovagal baroreflex sensitivity at 6 months for those initially randomized (p = 0.03), as well as those who crossed over from arms only exercise or waitlist control (p = 0.03 for each). However, amount of exercise performed and aerobic gains (VO2max) each poorly correlated with increases in cardiovagal baroreflex sensitivity (R2<0.15). In post-hoc analyses, individuals with paraplegia made significantly greater gains in baroreflex sensitivity compared to those with tetraplegia (p = 0.02), though gains within this group were again poorly correlated to gains in aerobic capacity. Clinicaltrials.gov number NCT02139436.

Digital Phenotyping to Quantify Psychosocial Well-Being Trajectories After Spinal Cord Injury.

OBJECTIVE: The aim of the study was to explore feasibility of smartphone-based digital phenotyping methods to examine depression and its relation to psychosocial well-being indicators after spinal cord injury. DESIGN: Smartphone research platform obtained smartphone sensor and survey data among community-living adult wheelchair users with spinal cord injury. Weekly measurements for 4 mos included Patient Health Questionnaire 8, Spinal Cord Injury-Quality of Life Satisfaction with and ability to participate in social roles and activities, global positioning system-derived community mobility metrics, health conditions, and physical activity. RESULTS: Forty-three individuals were enrolled. Study retention was higher among individuals offered financial incentives (78%) compared with participants enrolled before incentives (50%). Participants who dropped out more commonly had nontraumatic or acute spinal cord injury, were older, and had less satisfaction and lower participation in social roles and activities. Among 15 individuals with complete data, half had 1 wk or more of mild depression. Those with depression had frequent health issues, less satisfaction, and lower participation in social roles and activities. Those without depression experienced increased social engagement over time. Average community mobility was similar across depression groups. Relationships were typically in-phase but also varied by individual. CONCLUSIONS: Smartphone-based digital phenotyping of psychosocial well-being after spinal cord injury is feasible but not without attrition challenges. Individual differences in depression patterns highlight clinical utility of scaling these methods.

Relative contributions of systemic hemodynamic variables to cerebral autoregulation during orthostatic stress.

Postural changes impair the ability of the cerebrovasculature to buffer against dynamic pressure fluctuations, but the mechanisms underlying this impairment have not been elucidated. We hypothesized that autoregulatory impairment may reflect the impact of static central volume shifts on hemodynamic factors other than arterial pressure (AP). In 14 young volunteers, we assessed the relation of fluctuations in cerebral blood flow (CBF) to those in AP, cardiac output, and CO2, during oscillatory lower body pressure (LBP) (±20 mmHg at 0.01 and 0.06 Hz) at three static levels (-20, 0, and +20 mmHg). Static and dynamic changes in AP, cardiac output, and CO2 explained over 70% of the variation in CBF fluctuations. However, their contributions were different across frequencies and levels: dynamic AP changes explained a substantial proportion of the variation in faster CBF fluctuations (partial R2 = 0.75, standardized ß = 0.83, P < 0.01), whereas those in CO2 explained the largest portion of the variation in slow fluctuations (partial R2 = 0.43, ß = 0.51, P < 0.01). There was, however, a major contribution of slow dynamic AP changes during negative (ß = 0.43) but not neutral (ß = 0.05) or positive (ß = -0.07) LBP. This highlights the differences in contributions of systemic variables to dynamic and static autoregulation and has important implications for understanding orthostatic intolerance. NEW & NOTEWORTHY While fluctuations in blood pressure drive faster fluctuations in cerebral blood flow, overall level of CO2 and the magnitude of its fluctuations, along with cardiac output, determine the magnitude of slow ones. The effect of slow blood pressure fluctuations on cerebrovascular responses becomes apparent only during pronounced central volume shifts (such as when standing). This underlines distinct but interacting contributions of static and dynamic changes in systemic hemodynamic variables to the cerebrovascular regulation.

The Relationship between Cerebral Vasoreactivity and Post-Concussive Symptom Severity.

While pathophysiology underlying post-concussion symptom burden is unknown, data suggest that cerebrovascular dysfunction may be among the culprits. We sought to determine whether the degree of impairment in the ability of cerebrovasculature to buffer against changes in arterial gases (vasoreactivity) is associated with concussion symptoms. In 15 participants (19 ± 5 years, 1 week to 1 year post-injury) diagnosed with concussion, we assessed vasoreactivity from the slope of the linear relationship of beat-by-beat middle cerebral artery blood flow velocity (transcranial Doppler ultrasound) to end-tidal CO2 during progressive increases in end-tidal CO2 (air rebreathing). Symptom burden was assessed using the Post-Concussion Symptom Scale. Subsequently, we explored the relationship between vasoreactivity and the severity of post-concussion headache and cognitive difficulties by linear models. During rebreathing, CO2 increased from 32.6 ± 1.6 to 46.8 ± 1.8 mmHg and cerebrovascular conductance (i.e., flow velocity over pressure) increased from 0.48 ± 0.04 to 0.74 ± 0.06 cms-1 mmHg-1. There was a strong linear relationship between the increase in CO2 and in conductance (R2 = 0.81 ± 0.05; p < 0.05). On average, cerebral vasoreactivity was 0.018 ± 0.003 cm-1 s-1 mmHg CO2-1. Although vasoreactivity tended to be somewhat higher in the asymptotic participants (0.019 ± 0.003 vs. 0.015 ± 0.005 cm-1 s-1 mmHg CO2-1), this difference was not statistically significant (p = 0.48). Higher vasoreactivity was strongly associated with more severe headaches (R2 = 0.57; p < 0.01) and worse cognitive symptoms (R2 = 0.71; p < 0.01). Thus, cerebral vasoreactivity relates strongly to post-concussive headache and cognitive symptom burden. This has significant implications for understanding the pathophysiology underlying post-concussive symptom burden and for devising effective treatment options.

Alterations in sympathetic neurovascular transduction during acute hypoxia in humans.

Resting vascular sympathetic outflow is significantly increased during and beyond exposure to acute hypoxia without a parallel increase in either resistance or pressure. This uncoupling may indicate a reduction in the ability of sympathetic outflow to effect vascular responses (sympathetic transduction). However, the effect of hypoxia on sympathetic transduction has not been explored. We hypothesized that transduction would either remain unchanged or be reduced by isocapnic hypoxia. In 11 young healthy individuals, we measured beat-by-beat pressure, multiunit sympathetic nerve activity, and popliteal blood flow velocity at rest and during isometric handgrip exercise to fatigue, before and during isocapnic hypoxia (~80% SpO2), and derived sympathetic transduction for each subject via a transfer function that reflects Poiseuille's law of flow. During hypoxia, heart rate and sympathetic nerve activity increased, whereas pressure and flow remained unchanged. Both normoxic and hypoxic exercise elicited significant increases in heart rate, pressure, and sympathetic activity, although sympathetic responses to hypoxic exercise were blunted. Hypoxia slightly increased the gain relation between pressure and flow (0.062 ± 0.006 vs. 0.074 ± 0.004 cm·s(-1)·mmHg(-1); P = 0.04), but markedly increased sympathetic transduction (-0.024 ± 0.005 vs. -0.042 ± 0.007 cm·s(-1)·spike(-1); P < 0.01). The pressor response to isometric handgrip was similar during normoxic and hypoxic exercise due to the balance of interactions among the tachycardia, sympathoexcitation, and transduction. This indicates that the ability of sympathetic activity to affect vasoconstriction is enhanced during brief exposure to isocapnic hypoxia, and this appears to offset the potent vasodilatory stimulus of hypoxia.

Effect of systolic blood pressure and carotid stiffness on baroreflex gain in elderly subjects.

BACKGROUND: Aging is associated with diminished baroreflex sensitivity (gain), which predisposes elderly people to orthostatic hypotension, syncope, and cardiovascular morbidity. Aging is also associated with systolic blood pressure (SBP) elevation and carotid artery stiffness, which may both affect baroreflex gain. METHODS: We examined the relation between SBP, carotid artery stiffness, and baroreflex gain in 34 healthy elderly (71 +/- 4 years) and 10 healthy young (31 +/- 3 years) subjects. SBP (Finapres) and carotid artery stiffness (ultrasound measures of relative carotid artery diameter changes during each blood pressure pulse) were measured. The gain of the transfer function relating the R-R interval to SBP fluctuations at a frequency of 0.05-0.15 Hz was used to assess cardiovagal baroreflex gain. RESULTS: Elderly subjects had higher carotid artery stiffness (14.2 +/- 5.1 vs 6.6 +/- 1.8, p <.05), higher SBP (146 +/- 24 vs 125 +/- 8 mmHg, p =.012), and lower baroreflex gain (8.2 +/- 6.4 vs 16.3 +/- 7.4, p <.05) than young subjects. Among all subjects, SBP and carotid artery stiffness both correlated with baroreflex gain (r = -.39, p =.02 for both). Although SBP was related to stiffness across all subjects, this relation was not present among the elderly subjects. Within the elderly group, only SBP was independently related to baroreflex gain (R(2) =.51, p =.009). CONCLUSIONS: SBP elevation in elderly people may affect the neural or cardiac response to blood pressure fluctuations, independent of the mechanical properties of barosensory regions in the carotid artery. Future studies should examine the effect of pharmacologic treatment of hypertension on baroreflex gain in elderly people.