Craig D. Steinback

Objective Current guidelines suggest limiting physical activity in pregnant individuals carrying twins but this recommendation is not based on empirical evidence. We assessed maternal and fetal cardiovascular response to submaximal exercise testing in singleton versus twin pregnancies. Methods Females with a singleton (n=12, 26±5 weeks of gestation, 33±3 years of age) and twin (n=12, 26±5 weeks of gestation, 33±2 years of age) pregnancies were recruited. Maternal cardiac function (heart rate (HR); cardiac output (CO), stroke volume (SV) and ejection fraction (EF) via echocardiography) and mean arterial pressure (MAP; photoplethysmography) were measured at rest and during incremental cycling exercise to 70% HR reserve. Fetal HR and umbilical blood flow were measured pre-exercise and post-exercise. Results Compared to those with singleton pregnancies, women pregnant with twins had a higher resting HR (95±12 vs 83±6 bpm; p=0.003) and MAP (91±8 vs 82±9 mm Hg; p=0.013), but similar to SV, EF and CO. In response to a submaximal cycling exercise test, individuals with twins and singletons had similar changes in HR (Δ46±22 vs Δ56±11 bpm; p=0.16), CO (Δ6.2±3.9 vs Δ7.2±2.8 L/min; p=0.50), and ΔMAP (Δ14±7 vs Δ15±6 mm Hg; p=0.75). Fetal HR was unchanged in response to exercise at 70% HR reserve in both groups (singleton: Δ−1±4 vs twin: Δ0±4; p=0.53), with no incidence of fetal bradycardia or tachycardia. Umbilical blood flow was unchanged. Conclusion While resting haemodynamics were generally higher in individuals with twin compared with singleton pregnancies, the cardiovascular response to exercise was not different between groups and exercise did not impact fetal well-being.

High‐altitude hypoxia elicits several profound physiological responses, including substantial increases in muscle sympathetic nerve activity (MSNA); however, the association of this heightened MSNA with cardiovascular and cerebrovascular haemodynamics remains unclear in lowlanders and indigenous highlander populations. We hypothesized that at high altitude resting MSNA would be associated with resting cardiovascular and cerebrovascular haemodynamics in lowlanders ( n = 26), and Sherpa ( n = 8) and Andean ( n = 23) indigenous highlanders. Data were retrospectively analysed from two separate high‐altitude expeditions to Nepal (2016; 5050 m) and Peru (2018; 4300 m). We assessed resting MSNA via radial or peroneal microneurography, and measured , heart rate, mean arterial pressure, brachial artery blood flow and endothelial function, and internal carotid and vertebral artery diameter, velocity, and blood flow. Resting MSNA demonstrated limited, population‐specific associations with vascular haemodynamics. Lowlanders showed the most consistent relationships, including positive associations between MSNA and heart rate, vertebral artery diameter and blood flow, and internal carotid artery velocity, while Sherpa and Andean highlanders showed few systemic or cerebrovascular associations with MSNA. No relationship was observed between MSNA and , brachial artery blood flow or endothelial function across populations. Sensitivity analysis confirmed that most directional relationships were robust to the removal of influential participants, although some associations, including the negative relationship between MSNA and brachial artery blood flow in Sherpa, were attenuated. These data highlight that single time‐point, resting MSNA may have limited predictive value for cardiovascular and cerebrovascular haemodynamics at high altitude within these specific populations; however, these data should be interpreted with caution, given the small cross‐sectional sample sizes.

This study provides insight into the mechanisms involved in the sympathetic control of blood pressure at rest and in response to autonomic stress in different populations at high altitude. We demonstrate that resting blood pressure regulation is mediated primarily through α-adrenergic mechanisms in both lowlanders and Indigenous Andean highlanders at high altitude. However, pressor responses to apneic stress appear to be regulated by an alternative mechanism, particularly in highlanders who require less sympathetic activation.

Background: Cardiovascular disease is a primary driver of mortality in COPD. Elevated sympathetic nerve activity is a key proposed mechanism, but the magnitude of this autonomic overactivity has not been quantified in a pooled analysis. Objective: To determine if adults with COPD exhibit higher resting muscle sympathetic nerve activity (MSNA) than healthy controls, assess associated cardiorespiratory effects, and evaluate the short-term impact of COPD interventions on MSNA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight databases were searched from inception to 15 May 2025 to inform this systematic review and meta-analysis (PROSPERO CRD420251044931). Eligible studies included adults with spirometry-defined COPD in whom MSNA was measured by microneurography at rest. Primary outcomes were MSNA burst frequency (bursts·min ⁻¹ ) and incidence (bursts per 100 heartbeats). Secondary outcomes included resting heart rate and blood pressure. Results: A total of 11 studies (171 COPD participants, 105 controls) met inclusion criteria. Compared with controls, COPD was associated with markedly higher MSNA, burst frequency (+18.5, 95% CI 9.4–27.7 bursts·min ⁻¹ ) and burst incidence (+21.3, 95% CI 9.2–33.4 bursts per 100 heartbeats). Resting heart rate was also elevated (+10.7, 95% CI 6.1–15.3 beats·min ⁻¹ ), while blood pressure did not differ significantly. Three studies on noninvasive ventilation or inhaled β ₂ -agonists found no significant pooled changes in MSNA. Conclusions: Resting MSNA is significantly elevated in patients with COPD despite normal blood pressure. This chronic sympathetic excitation likely contributes to COPD-related cardiovascular morbidity and exercise intolerance, highlighting the importance of developing therapies that reduce sympathetic nerve activity.

This study examined how sex influences blood flow during exercise at altitude and relative contributions of adrenergic mechanisms. Thirteen participants (8 M/5F) were tested at low and high altitude (days 3–11). Participants performed rhythmic handgrip for 3 min at 25% maximal voluntary contraction during local infusions of saline, propranolol (β‐adrenergic blockade), and phentolamine with propranolol (α‐β‐adrenergic blockade). Doppler ultrasound was used to examine brachial artery blood flow (FBF) and calculate forearm vascular conductance (FVC). Resting FBF and FVC were higher in males compared to females across all conditions ( p = 0.024; p = 0.025, respectively). Blockade condition significantly altered FBF and FVC ( p < 0.001 for both) but there was no effect of altitude ( p = 0.330; p = 0.718, respectively). During exercise, ΔFBF was influenced by condition ( p < 0.001), but not by sex ( p = 0.696) or altitude ( p = 0.813). Similarly, ΔFVC was different across conditions (control: 9.4 ± 2.3 mL/min/mmHg/FAV; β‐blockade: 11.4 ± 12.8 mL/min/mmHg/FAV; α‐β‐blockade: 3.9 ± 1.1 mL/min/mmHg/FAV; p < 0.001), with no effect of sex ( p = 0.646) or altitude ( p = 0.889). These results suggest males and females do not respond differently to exercise at altitude, and light‐intensity exercise hyperemia may be preserved during early acclimatization. α‐adrenergic receptors appear important for exercising blood flow, but β‐adrenergic receptors may not be critical in this response.

Apneas performed during hypoxia cause pronounced bradycardia and cardiac arrhythmias. What remains unclear is the intraindividual consistency of these responses. Therefore, we assessed the within‐day and between‐day repeatability of responses to hypoxic apneas, including the genesis of arrhythmias or electrocardiogram (ECG) changes. Sixteen participants (8F/8M, 25 ± 3 years, BMI 23.7 ± 3.4 kg/m ² , mean ± SD) completed four hypoxic apneas per day on consecutive days, time‐matched to a maximal apnea on day 1 (39 ± 16 s). We quantified heart rate (HR) and mean arterial pressure (MAP) repeatability using within‐subject standard deviations (WSSD), [95%CI]. We hypothesized that WSSDs would be <5 bpm and <4 mmHg for HR and MAP. We also assessed the repeatability of arrhythmias or ECG changes. Within‐day, the HR WSSD was 4.4 bpm [3.7, 5.6], and the MAP WSSD was 4.1 mmHg [3.4, 5.1]. Between‐day comparisons had somewhat higher WSSDs: HR was 5.7 bpm [5.0, 6.5] and MAP was 5.0 mmHg [4.4, 5.8]. Arrhythmias or ECG changes occurred during 45% of apneas. These data indicate poor repeatability of electrical conduction changes during apneas. Conversely, our WSSD data indicate good within‐day and between‐day repeatability, albeit somewhat higher than hypothesized. These data therefore indicate that hypoxic apneas are a repeatable laboratory stressor for HR and MAP, but that researchers should exercise caution in interpreting individual‐level arrhythmia data.

Pregnant women who were exposed to 14-wk aerobic exercise training intervention have increased miR-21-3p levels in plasma accompanied by an attenuation in the increase of burst incidence across pregnancy.

Central command, muscle afferent feedback and arterial baroreceptors all contribute to sympathetic vasoconstrictor activity during moderate‐intensity dynamic exercise in humans; however, whether a causal link exists between pulmonary arterial mechanoreceptors and sympathetic outflow directed to inactive skeletal muscle (muscle sympathetic nerve activity, MSNA) remains to be explored. Twelve participants (28 ± 7 years, 2 females) performed two 6 min exercise bouts (heart rate ∼ 120∙beats∙min⁻¹) in hypoxia (FiO_2 = 12.5%) to elevate pulmonary artery pressure (PAP) above normal, whilst MSNA (microneurography), systemic blood pressure (photoplethysmography, BP), oxygen saturation (SpO₂) and minute ventilation (V_E) were measured continuously. Systolic PAP was estimated using Doppler echocardiography. In one trial nitric oxide was added to the inhaled air (iNO, 40 parts per million) to selectively dilate the pulmonary vasculature and reduce exercise PAP. MSNA burst frequency was supressed (30 ± 9 vs. 34 ± 9 bursts∙min⁻¹; p = 0.03) when exercise systolic PAP was lowered (36.8 vs. 42.9 ± 8 mmHg; p = 0.02). MSNA burst incidence (index of sympathetic baroreflex operating point) was reduced (25 ± 8 vs. 28 ± 9 bursts∙100 heartbeats⁻¹; p = 0.03) without any change in corresponding diastolic BP or spontaneous baroreflex gain. Mean BP, SpO₂ and V_E did not differ between trials. Together these data support a mechanistic link between pulmonary arterial mechanoreceptor activation and neurocirculatory control during hypoxic exercise. The effect of pulmonary arterial mechanoreceptor activity on exercise‐induced sympathetic activation and baroreflex resetting may have consequences for sympathetic vasomotor outflow (dys)regulation in health and disease where PAP is elevated. image Key points: Pulmonary arterial pressure increases proportionally to cardiac output during dynamic exercise; this pressure rise may contribute to excitation of sympathetic vasoconstrictor activity directed to skeletal muscle (muscle sympathetic nerve activity, MSNA) via stimulation of pulmonary arterial mechanoreceptors. In this study addition of nitric oxide to hypoxic inspired air (FiO₂ = 12.5%) reduced pulmonary arterial pressure during sub‐maximal cycling exercise; this coincided with reduced MSNA burst frequency (vasoconstrictor outflow) and burst incidence (operating point for baroreflex control of vasoconstrictor outflow). These findings demonstrate that a signal from pulmonary arterial mechanoreceptors is involved in sympathoexcitation during hypoxic exercise. Furthermore this mechanism could be relevant clinically in pulmonary and cardiac diseases associated with pulmonary hypertension and exaggerated sympathoexcitation during exercise.