The Impact of Exercise Training on Muscle Sympathetic Nerve Activity: A Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis was to examine the effects of exercise training on muscle sympathetic nerve activity (MSNA) in humans. Studies included exercise interventions (randomized controlled trials [RCTs], non-randomized controlled trials [non-RCTs] or pre-to-post intervention) that reported on adults (>18 years) where MSNA was directly assessed using microneurography, and relevant outcomes were assessed (MSNA [total activity, burst frequency, burst incidence, amplitude], heart rate, blood pressure [systolic blood pressure, diastolic blood pressure, or mean blood pressure], and aerobic capacity [maximal or peak oxygen consumption]). 40 intervention studies (n=1,253 individuals) were included. RCTs of exercise compared to no exercise illustrated that those randomized to the exercise intervention had a significant reduction in MSNA burst frequency and incidence compared to controls. This reduction in burst frequency was not different between individuals with cardiovascular disease compared to those without. However, the reduction in burst incidence was greater in those with cardiovascular disease (9 RCTs studies, n = 234, MD -21.08 bursts/100 hbs; 95% CI -16.51, -25.66; I2 = 63%) compared to those without (6 RCTs, n = 192, MD -10.92 bursts/100 hbs; 95% CI -4.12, -17.73; I2 = 76%). Meta-regression analyses demonstrated a dose-response relationship where individuals with higher burst frequency and incidence pre-intervention had a greater reduction in values post-intervention. These findings suggest that exercise training reduces muscle sympathetic nerve activity, which may be valuable for improving cardiovascular health.

The effect of hyperoxia on muscle sympathetic nerve activity: a systematic review and meta-analysis.

PURPOSE: We conducted a meta-analysis to determine the effect of hyperoxia on muscle sympathetic nerve activity in healthy individuals and those with cardio-metabolic diseases. METHODS: A comprehensive search of electronic databases was performed until August 2022. All study designs (except reviews) were included: population (humans; apparently healthy or with at least one chronic disease); exposures (muscle sympathetic nerve activity during hyperoxia or hyperbaria); comparators (hyperoxia or hyperbaria vs. normoxia); and outcomes (muscle sympathetic nerve activity, heart rate, blood pressure, minute ventilation). Forty-nine studies were ultimately included in the meta-analysis. RESULTS: In healthy individuals, hyperoxia had no effect on sympathetic burst frequency (mean difference [MD] - 1.07 bursts/min; 95% confidence interval [CI] - 2.17, 0.04bursts/min; P = 0.06), burst incidence (MD 0.27 bursts/100 heartbeats [hb]; 95% CI - 2.10, 2.64 bursts/100 hb; P = 0.82), burst amplitude (P = 0.85), or total activity (P = 0.31). In those with chronic diseases, hyperoxia decreased burst frequency (MD - 5.57 bursts/min; 95% CI - 7.48, - 3.67 bursts/min; P < 0.001) and burst incidence (MD - 4.44 bursts/100 hb; 95% CI - 7.94, - 0.94 bursts/100 hb; P = 0.01), but had no effect on burst amplitude (P = 0.36) or total activity (P = 0.90). Our meta-regression analyses identified an inverse relationship between normoxic burst frequency and change in burst frequency with hyperoxia. In both groups, hyperoxia decreased heart rate but had no effect on any measure of blood pressure. CONCLUSION: Hyperoxia does not change sympathetic activity in healthy humans. Conversely, in those with chronic diseases, hyperoxia decreases sympathetic activity. Regardless of disease status, resting sympathetic burst frequency predicts the degree of change in burst frequency, with larger decreases for those with higher resting activity.

The effect of hypoxemia on muscle sympathetic nerve activity and cardiovascular function: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to determine the effect of acute poikilocapnic, high-altitude, and acute isocapnia hypoxemia on muscle sympathetic nerve activity (MSNA) and cardiovascular function. A comprehensive search across electronic databases was performed until June 2021. All observational designs were included: population (healthy individuals); exposures (MSNA during hypoxemia); comparators (hypoxemia severity and duration); outcomes (MSNA; heart rate, HR; and mean arterial pressure, MAP). Sixty-one studies were included in the meta-analysis. MSNA burst frequency increased by a greater extent during high-altitude hypoxemia [P < 0.001; mean difference (MD), +22.5 bursts/min; confidence interval (CI) = -19.20 to 25.84] compared with acute poikilocapnic hypoxemia (P < 0.001; MD, +5.63 bursts/min; CI = -4.09 to 7.17) and isocapnic hypoxemia (P < 0.001; MD, +4.72 bursts/min; CI = -3.37 to 6.07). MSNA burst amplitude was only elevated during acute isocapnic hypoxemia (P = 0.03; standard MD, +0.46 au; CI = -0.03 to 0.90), and MSNA burst incidence was only elevated during high-altitude hypoxemia [P < 0.001; MD, 33.05 bursts/100 heartbeats; CI = -28.59 to 37.51]. Meta-regression analysis indicated a strong relationship between MSNA burst frequency and hypoxemia severity for acute isocapnic studies (P < 0.001) but not acute poikilocapnia (P = 0.098). HR increased by the same extent across each type of hypoxemia [P < 0.001; MD +13.81 heartbeats/min; 95% CI = 12.59-15.03]. MAP increased during high-altitude hypoxemia (P < 0.001; MD, +5.06 mmHg; CI = 3.14-6.99), and acute isocapnic hypoxemia (P < 0.001; MD, +1.91 mmHg; CI = 0.84-2.97), but not during acute poikilocapnic hypoxemia (P = 0.95). Both hypoxemia type and severity influenced sympathetic nerve and cardiovascular function. These data are important for the better understanding of healthy human adaptation to hypoxemia.

Increased stiffness of omental arteries from late pregnant women at advanced maternal age.

Advanced maternal age (≥35 years) is a risk factor for poor pregnancy outcomes. Pregnancy requires extensive maternal vascular adaptations, and with age, our blood vessels become stiffer and change in structure (collagen and elastin). However, the effect of advanced maternal age on the structure of human resistance arteries during pregnancy is unknown. As omental resistance arteries contribute to blood pressure regulation, assessing their structure in pregnancy may inform on the causal mechanisms underlying pregnancy complications in women of advanced maternal age. Omental fat biopsies were obtained from younger (<35 years) or advanced maternal age (≥35 years) women during caesarean delivery (n = 7-9/group). Arteries (200-300 µm) were isolated and passive mechanical properties (circumferential stress and strain) assessed with pressure myography. Collagen (Masson's Trichrome) and elastin (Verhoff) were visualized histologically and % positively-stained area was assessed. Median maternal age was 32 years (range 25-34) for younger, and 38 years (range 35-42) for women of advanced maternal age. Circumferential strain was lower in arteries from advanced maternal age versus younger women but circumferential stress was not different. Omental artery collagen levels were similar, while elastin levels were lower with advanced maternal age versus younger pregnancies. The collagen:elastin ratio was greater in arteries from advanced maternal age versus younger women. In conclusion, omental arteries from women of advanced maternal age were less compliant with less elastin compared with arteries of younger controls, which may affect how vascular stressors are tolerated during pregnancy. Understanding how vascular aging affects pregnancy adaptations may contribute to better pregnancy outcomes.

Increased respiratory modulation of cardiovascular control reflects improved blood pressure regulation in pregnancy.

Hypertensive pregnancy disorders put the maternal-fetal dyad at risk and are one of the leading causes of morbidity and mortality during pregnancy. Multiple efforts have been made to understand the physiological mechanisms behind changes in blood pressure. Still, to date, no study has focused on analyzing the dynamics of the interactions between the systems involved in blood pressure control. In this work, we aim to address this question by evaluating the phase coherence between different signals using wavelet phase coherence. Electrocardiogram, continuous blood pressure, electrocardiogram-derived respiration, and muscle sympathetic nerve activity signals were obtained from ten normotensive pregnant women, ten normotensive non-pregnant women, and ten pregnant women with preeclampsia during rest and cold pressor test. At rest, normotensive pregnant women showed higher phase coherence in the high-frequency band (0.15-0.4 Hz) between muscle sympathetic nerve activity and the RR interval, blood pressure, and respiration compared to non-pregnant normotensive women. Although normotensive pregnant women showed no phase coherence differences with respect to hypertensive pregnant women at rest, higher phase coherence between the same pairs of variables was found during the cold pressor test. These results suggest that, in addition to the increased sympathetic tone of normotensive pregnant women widely described in the existing literature, there is an increase in cardiac parasympathetic modulation and respiratory-driven modulation of muscle sympathetic nerve activity and blood pressure that could compensate sympathetic increase and make blood pressure control more efficient to maintain it in normal ranges. Moreover, blunted modulation could prevent its buffer effect and produce an increase in blood pressure levels, as observed in the hypertensive women in this study. This initial exploration of cardiorespiratory coupling in pregnancy opens the opportunity to follow up on more in-depth analyses and determine causal influences.

Muscle sympathetic nerve activity during pregnancy: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to quantify the impact of healthy and complex pregnancy on muscle sympathetic nerve activity (MSNA) at rest, and in response to stress. Structured searches of electronic databases were performed until February 23, 2022. All study designs (except reviews) were included: population (pregnant individuals); exposures (healthy and complicated pregnancy with direct measures of MSNA); comparator (individuals who were not pregnant, or with uncomplicated pregnancy); and outcomes (MSNA, BP, and heart rate). Twenty-seven studies (N = 807) were included. MSNA burst frequency was higher in pregnancy (n = 201) versus non-pregnant controls (n = 194) (Mean Differences [MD], MD: 10.6 bursts/min; 95% CI: 7.2, 14.0; I2  = 72%). Accounting for the normative increase in heart rate with gestation, burst incidence was also higher during pregnancy (Pregnant N = 189, non-pregnant N = 173; MD: 11 bpm; 95% CI: 8, 13 bpm; I2  = 47%; p < 0.0001). Meta-regression analyses confirmed that although sympathetic burst frequency and incidence are augmented during pregnancy, this was not significantly associated with gestational age. Compared to uncomplicated pregnancy, individuals with obesity, obstructive sleep apnea, and gestational hypertension exhibited sympathetic hyperactivity, while individuals with gestational diabetes mellitus or preeclampsia did not. Uncomplicated pregnancies exhibited a lesser response to head-up tilt, but an exaggerated sympathetic responsiveness to cold pressor stress compared to non-pregnant individuals. MSNA is higher in pregnant individuals and further increased with some, but not all pregnancy complications. PROSPERO registration number: CRD42022311590.

Prenatal Exercise and Cardiovascular Health (PEACH) study: impact of meal timing and pre-exercise blood glucose values on glycemic responses to acute exercise in pregnancy.

We retrospectively analyzed data from 28 participants engaging in moderate-intensity aerobic exercise (265 sessions; 25-40 min) between 18-34 weeks gestation (NCT02948439). The mean change in blood glucose (BG) from pre- to post-acute exercise session was -1.0 ± 1.2 mmol/L. Pre-exercise BG significantly predicted the change in BG (p < 0.001), even when controlling for meal timing, exercise duration, and gestational age. Hypoglycemia only occurred in 3% of sessions. Therefore, in healthy pregnancy the change in BG during exercise is small and primarily related to pre-exercise BG values.

The influence of training status and parasympathetic blockade on the cardiac rate, rhythm, and functional response to autonomic stress.

Apnea (breath-holding) elicits co-activation of sympathetic and parasympathetic nervous systems, affecting cardiac control. In situations of autonomic co-activation (e.g., cold water immersion), cardiac arrhythmias are observed during apnea. Chronic endurance training reduces resting heart rate in part via elevation in parasympathetic tone, and has been identified as a risk factor for development of arrhythmias. However, few studies have investigated autonomic control of the heart in trained athletes during stress. Therefore, we determined whether heightened vagal tone resulting from endurance training promotes a higher incidence of arrhythmia during apnea. We assessed the heart rate, rhythm (ECG lead II), and cardiac inotropic (speckle-tracking echocardiography) response to apnea in 10 endurance trained and 7 untrained participants. Participants performed an apnea at rest and following sympathetic activation using post-exercise circulatory occlusion (PECO). All apneas were performed prior to control (CON) and following vagal block using glycopyrrolate (GLY). Trained participants had lower heart rates at rest (p = 0.03) and during apneas (p = 0.009) under CON. At rest, 3 trained participants exhibited instances of junctional rhythm and 4 trained participants developed ectopy during CON apneas, whereas 3 untrained participants developed ectopic beats only with concurrent sympathetic activation (PECO). Following GLY, no arrhythmias were noted in either group. Vagal block also revealed increased cardiac chronotropy (heart rate) and inotropy (strain rate) during apnea, demonstrating a greater sympathetic influence in the absence of parasympathetic drive. Our results highlight that endurance athletes may be more susceptible to ectopy via elevated vagal tone, whereas untrained participants may only develop ectopy through autonomic conflict.

The sympathetic nervous system in healthy and hypertensive pregnancies: physiology or pathology?

NEW FINDINGS: What is the topic of this review? Sympathoexcitation in both healthy and hypertensive pregnancies, and concurrent adaptations along the neurovascular cascade. What advances does it highlight? Known and plausible adaptations along the neurovascular cascade which may offset elevated MSNA in normotensive pregnancy while also highlighting knowledge gaps regarding understudied pathways. ABSTRACT: The progression from conception through to the postpartum period represents an extraordinary period of physiological adaptation in the mother to support the growth and development of the fetus. Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and sympathetic nerve activity, yet normal or reduced blood pressure; it represents a unique period of apparent healthy sympathetic hyperactivity. However, how this normal blood pressure is achieved in the face of sympathoexcitation, and the mechanisms responsible for this increased activity are unclear. Importantly, sympathetic activation has been implicated in hypertensive pregnancy disorders - the leading causes of maternal-fetal morbidity and mortality in the developed world. An understudied link between pregnancy and the development of maternal hypertension may lie in the sympathetic nervous system regulation of blood pressure. This brief review presents the latest data on sympathoexcitation in both healthy and hypertensive pregnancies, and concurrent adaptations along the neurovascular cascade.

Prenatal Exercise and Cardiovascular Health (PEACH) Study: impact of pregnancy and exercise on rating of perceived exertion during non-weight-bearing exercise.

The purpose of this study was to determine if rating of perceived exertion (RPE) during non-weight-bearing exercise is influenced by gestational age and exercise training. We conducted a randomized controlled trial to examine the influence of gestational age and exercise training (three to four times per week for 25-40 minutes at 50%-70% of heart rate reserve) on RPE during an exhaustive cycling exercise test. We observed no influence of gestational age, or exercise training status on RPE responses to non-weight-bearing exercise during pregnancy. Trial registration number: NCT02948439. Novelty: Gestational age and/or exercise training does not influence rate of perceived exertion during non-weight-bearing exercise.

Influence of Obstructive Sleep Apnea Severity on Muscle Sympathetic Nerve Activity and Blood Pressure: a Systematic Review and Meta-Analysis.

BACKGROUND: We conducted meta-analyses to identify relationships between obstructive sleep apnea (OSA) severity, muscle sympathetic nerve activity (MSNA), and blood pressure (BP). We quantified the effect of OSA treatment on MSNA. METHODS: Structured searches of electronic databases were performed until June 2021. All observational designs (except reviews) were included: population (individuals with OSA); exposures (OSA diagnosis and direct measures of MSNA); comparator (individuals without OSA or different severity of OSA); outcomes (MSNA, BP, and heart rate). RESULTS: Fifty-six studies (N=1872) were included. MSNA burst frequency was higher in OSA (27 studies; n=542) versus controls (n=488; mean differences [MDs], +15.95 bursts/min [95% CI, 12.6-17.6 bursts/min]; I2=86%). As was burst incidence (20 studies; n=357 OSA, n=312 Controls; MD, +22.23 bursts/100 hbs [95% CI, 18.49-25.97 bursts/100 hbs]; I2=67%). Meta-regressions indicated relationships between MSNA and OSA severity (burst frequency, R2=0.489; P<0.001; burst incidence, R2=0.573; P<0.001). MSNA burst frequency was related to systolic pressure (R2=0.308; P=0.016). OSA treatment with continuous positive airway pressure reduced MSNA burst frequency (MD, 11.91 bursts/min [95% CI, 9.36-14.47 bursts/min] I2=15%) and systolic (n=49; MD, 10.3 mm Hg [95% CI, 3.5-17.2 mm Hg]; I2=42%) and diastolic (MD, 6.9 mm Hg [95% CI, 2.3-11.6 mm Hg]; I2=37%) BP. CONCLUSIONS: MSNA is higher in individuals with OSA and related to severity. This sympathoexcitation is also related to BP in patients with OSA. Treatment effectively reduces MSNA and BP, but limited data prevents an assessment of the link between these reductions. These data are clinically important for understanding cardiovascular disease risk in patients with OSA. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42021285159.

Cerebrovascular and blood pressure responses during voluntary apneas are larger than rebreathing.

Both voluntary rebreathing (RB) of expired air and voluntary apneas (VA) elicit changes in arterial carbon dioxide and oxygen (CO2 and O2) chemostimuli. These chemostimuli elicit synergistic increases in cerebral blood flow (CBF) and sympathetic nervous system activation, with the latter increasing systemic blood pressure. The extent that simultaneous and inverse changes in arterial CO2 and O2 and associated increases in blood pressure affect the CBF responses during RB versus VAs are unclear. We instrumented 21 healthy participants with a finometer (beat-by-beat mean arterial blood pressure; MAP), transcranial Doppler ultrasound (middle and posterior cerebral artery velocity; MCAv, PCAv) and a mouthpiece with sample line attached to a dual gas analyzer to assess pressure of end-tidal (PET)CO2 and PETO2. Participants performed two protocols: RB and a maximal end-inspiratory VA. A second-by-second stimulus index (SI) was calculated as PETCO2/PETO2 during RB. For VA, where PETCO2 and PETO2 could not be measured throughout, SI values were calculated using interpolated end-tidal gas values before and at the end of the apneas. MAP reactivity (MAPR) was calculated as the slope of the MAP/SI, and cerebrovascular reactivity (CVR) was calculated as the slope of MCAv or PCAv/SI. We found that compared to RB, VA elicited ~ fourfold increases in MAPR slope (P < 0.001), translating to larger anterior and posterior CVR (P ≤ 0.01). However, cerebrovascular conductance (MCAv or PCAv/MAP) was unchanged between interventions (P ≥ 0.2). MAP responses during VAs are larger than those during RB across similar chemostimuli, and differential CVR may be driven by increases in perfusion pressure.

Acid-base balance at high altitude in lowlanders and indigenous highlanders.

High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH (pHa) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations-where the latter are thought to be fully adapted to high altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders and Andean and Sherpa highlanders at various altitudes (∼3,800, ∼4,300, and ∼5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n = 7) had elevated pHa compared with Sherpas (n = 12; P < 0.01), but not to lowlanders (n = 16; 9 days acclimatized; P = 0.09); 2) at 4,300 m, lowlanders (n = 16; 21 days acclimatized) had elevated pHa compared with Andeans (n = 32) and Sherpas (n = 11; both P < 0.01), and Andeans had elevated pHa compared with Sherpas (P = 0.01); and 3) at 5,000 m, lowlanders (n = 16; 14 days acclimatized) had higher pHa compared with both Andeans (n = 66) and Sherpas (n = 18; P < 0.01, and P = 0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P = 0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.NEW & NOTEWORTHY Lowlander, Andean, and Sherpa arterial blood data were combined across five independent high-altitude expeditions in the United States, Nepal, and Peru to assess acid-base status at ∼3,800, ∼4,300, and ∼5,000 m. The main finding was that Andean and Sherpa highlander populations have more acidic arterial blood, due to elevated arterial carbon dioxide and similar arterial bicarbonate compared with acclimatizing lowlanders at altitudes ≥4,300 m.

The effects of physical activity on arterial stiffness during pregnancy: an observational study.

The objective of the present study was to investigate the relationship between moderate-to-vigorous physical activity (MVPA) and arterial stiffness in pregnancy. Thirty-nine women participated in this study, resulting in 68 measurements in non-pregnant (NP; n = 21), first (TM1; n = 8), second (TM2; n = 20), and third trimesters (TM3; n = 19). Compliance, distensibility, elasticity, ß-stiffness, and carotid to femoral (central) and carotid to finger (peripheral) pulse wave velocity (PWV) were assessed. MVPA was measured using accelerometry. Multilevel linear regressions adjusted for multiple tests per participant using random effects to generate ß coefficients and 95% confidence intervals (CIs) were performed. Distensibility, elasticity, ß-stiffness, and central- and peripheral-PWV did not differ between pregnant and non-pregnant assessments. Carotid artery compliance was higher in TM2 compared with NP. Central PWV (ß coefficient: -0.14, 95% CI: -0.27, -0.02) decreased from early to mid-pregnancy and increased in late pregnancy. Meeting the MVPA guidelines was significantly associated with central-PWV (adjusted ß coefficient: -0.34, 95% CI: -0.62, -0.06, p = 0.016), peripheral-PWV (adjusted ß coefficient: -0.54, 95% CI: -0.91, -0.16, p = 0.005), and distensibility (adjusted ß coefficient: -0.001, 95% CI: -0.002, -0.0001, p = 0.018), in pregnancy. These results suggest that MVPA may be associated with improved (i.e., reduced) arterial stiffness in pregnancy. Novelty: Central PWV, distensibility, compliance, elasticity, and ß-stiffness, but not peripheral PWV, exhibited curvilinear relationships with gestational age Central and peripheral PWV were lower in pregnant women who met the physical activity guidelines of 150 minutes of moderate-to-vigorous physical activity per week.

Prenatal exercise and cardiovascular health (PEACH) study: impact of acute and chronic exercise on cerebrovascular hemodynamics and dynamic cerebral autoregulation.

We performed a randomized controlled trial measuring dynamic cerebral autoregulation (dCA) using a sit-to-stand maneuver before (SS1) and following (SS2) an acute exercise test at 16-20 wk gestation (trimester 2, TM2) and then again at 34-37 wk gestation (third trimester, TM3). Following the first assessment, women were randomized into exercise training or control (standard care) groups; women in the exercise training group were prescribed moderate intensity aerobic exercise for 25-40 min on 3-4 days per week for 14 ± 1 wk. Resting seated mean blood velocity in the middle cerebral artery (MCAvmean) was lower in TM3 than in TM2 but not impacted by exercise training intervention. No metric of dCA was impacted by gestational age or exercise training during SS1. During SS2, there were greater absolute and relative decreases in mean arterial blood pressure (MAP) and MCAvmean, but this was not impacted by the intervention. There was also no difference in the relationship between the decrease in MCAvmean compared with the decrease in MAP (%/%) or the onset of the regulatory response with respect to acute exercise, gestational age, or intervention; however, rate of regulation was faster in women in the exercise group following acute exercise (interaction effect, P = 0.048). These data highlight the resilience of the cerebral circulation in that dCA was well maintained or improved in healthy pregnant women between TM2 and TM3. However, future work addressing the impact of acute and chronic exercise on dCA in women who are at risk for cardiovascular complications during pregnancy is needed.NEW & NOTEWORTHY These data represent the first assessments of dynamic cerebral autoregulation in pregnancy using a sit-to-stand. We used a randomized controlled trial to show dynamic cerebral autoregulation is not impacted by gestational age or by chronic exercise. However, there are larger decreases in blood pressure and cerebral blood velocity following sit-to-stand after acute exercise without adverse events. These data highlight the adaptability of the cerebral circulation during pregnancy to accommodate large changes in the cardiovascular system.

Duration at high altitude influences the onset of arrhythmogenesis during apnea.

PURPOSE: Autonomic control of the heart is balanced by sympathetic and parasympathetic inputs. Excitation of both sympathetic and parasympathetic systems occurs concurrently during certain perturbations such as hypoxia, which stimulate carotid chemoreflex to drive ventilation. It is well established that the chemoreflex becomes sensitized throughout hypoxic exposure; however, whether progressive sensitization alters cardiac autonomic activity remains unknown. We sought to determine the duration of hypoxic exposure at high altitude necessary to unmask cardiac arrhythmias during instances of voluntary apnea. METHODS: Measurements of steady-state chemoreflex drive (SS-CD), continuous electrocardiogram (ECG) and SpO2 (pulse oximetry) were collected in 22 participants on 1 day at low altitude (1045 m) and over eight consecutive days at high-altitude (3800 m). SS-CD was quantified as ventilation (L/min) over stimulus index (PETCO2/SpO2). RESULTS: Bradycardia during apnea was greater at high altitude compared to low altitude for all days (p < 0.001). Cardiac arrhythmias occurred during apnea each day but became most prevalent (> 50%) following Day 5 at high altitude. Changes in saturation during apnea and apnea duration did not affect the magnitude of bradycardia during apnea (ANCOVA; saturation, p = 0.15 and apnea duration, p = 0.988). Interestingly, the magnitude of bradycardia was correlated with the incidence of arrhythmia per day (r = 0.8; p = 0.004). CONCLUSION: Our findings suggest that persistent hypoxia gradually increases vagal tone with time, indicated by augmented bradycardia during apnea and progressively increased the incidence of arrhythmia at high altitude.

Sympathetic neurovascular transduction following acute hypoxia.

PURPOSE: Following an acute exposure to hypoxia, sympathetic nerve activity remains elevated. However, this elevated sympathetic nerve activity does not elicit a parallel increase in vascular resistance suggesting a blunted sympathetic signaling [i.e. blunted sympathetic neurovascular transduction (sNVT)]. Therefore, we sought to quantify spontaneous sympathetic bursts and related changes in total peripheral resistance following hypoxic exposure. We hypothesized that following hypoxia sNVT would be blunted. METHODS: Nine healthy participants (n = 6 men; mean age 25 ± 2 years) were recruited. We collected data on muscle sympathetic nerve activity (MSNA) using microneurography and beat-by-beat total peripheral resistance (TPR) via finger photoplethysmography at baseline, during acute hypoxia and during two periods of recovery (recovery period 1, 0-10 min post hypoxia; recovery period 2, 10-20 min post hypoxia). MSNA burst sequences (i.e. singlets, doublets, triplets and quads+) were identified and coupled to changes in TPR over 15 cardiac cycles as an index of sNVT for burst sequences. A sNVT slope for each participant was calculated from the slope of the relationship between TPR plotted against normalized burst amplitude. RESULTS: The sNVT slope was blunted during hypoxia [Δ 0.0044 ± 0.0014 (mmHg/L/min)/(a.u.)], but unchanged following termination of hypoxia [recovery 1, Δ 0.031 ± 0.0019 (mmHg/L/min)/(a.u.); recovery 2, Δ 0.0038 ± 0.0014 (mmHg/L/min)/(a.u.) compared to baseline (Δ 0.038 ± 0.0015 (L/min/mmHg)/(a.u.)] (main effect of group p = 0.012). CONCLUSIONS: Contrary to our hypothesis, we have demonstrated that systemic sNVT is unchanged following hypoxia in young healthy adults.

The 9-Month Stress Test: Pregnancy and Exercise-Similarities and Interactions.

Of all physiological systems, the cardiovascular system takes on the most profound adaptation in pregnancy to support fetal growth and development. The adaptations that arise are systemic and involve structural and functional changes that can be observed at the cerebral, central, peripheral, and microvascular beds. This includes, although is not limited to, increased heart rate, stroke volume, and cardiac output with negligible change to blood pressure, reductions in vascular resistance, and cerebral blood flow velocity, systemic artery enlargement, and enhanced endothelial function. All of this takes place to accommodate blood volume expansion and ensure adequate fetal and maternal oxygen delivery. In some instances, the demand placed on the vasculature can manifest as cardiovascular maladaptation and thus, cardiovascular complications can arise. Exercise is recommended in pregnancy because of its powerful ability to reduce the incidence and severity of cardiovascular complications in pregnancy. However, the mechanism by which it acts is poorly understood. The first of our aims in this review was to describe the systemic adaptations that take place in pregnancy. Our second aim was to describe the influence of exercise on these systemic adaptations. It is anticipated that this review can comprehensively capture the extent of knowledge in this area while identifying areas that warrant further investigation.