Influence of hypercapnia and hypercapnic hypoxia on the heart rate response to apnea.

We aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would cause greater bradycardia than normoxia, similar to the response seen with hypoxia, and that apneas with hypercapnic hypoxia would induce greater bradycardia than hypoxia or hypercapnia alone. Twenty-six healthy participants (12 females; 23 ± 2 years; BMI 24 ± 3 kg/m2) underwent three gas challenges: hypercapnia (+5 torr end tidal partial pressure of CO2 [PETCO2]), hypoxia (50 torr end tidal partial pressure of O2 [PETO2]), and hypercapnic hypoxia (combined hypercapnia and hypoxia), with each condition interspersed with normocapnic normoxia. Heart rate and rhythm, blood pressure, PETCO2, PETO2, and oxygen saturation were measured continuously. Hypercapnic hypoxic apneas induced larger bradycardia (-19 ± 16 bpm) than normocapnic normoxic apneas (-11 ± 15 bpm; p = 0.002), but had a comparable response to hypoxic (-19 ± 15 bpm; p = 0.999) and hypercapnic apneas (-14 ± 14 bpm; p = 0.059). Hypercapnic apneas were not different from normocapnic normoxic apneas (p = 0.134). After removal of the normocapnic normoxic heart rate response, the change in heart rate during hypercapnic hypoxia (-11 ± 16 bpm) was similar to the summed change during hypercapnia+hypoxia (-9 ± 10 bpm; p = 0.485). Only hypoxia contributed to this bradycardic response. Under apneic conditions, the cardiac response is driven by hypoxia.

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 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.

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.