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 S p O 2 , 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 S p O 2 , 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.

Hot-water immersion (HWI) has been shown to reduce 24 h ambulatory systolic blood pressure in hypertensive adults and might represent a preventative strategy for maintaining cardiovascular health in normotensive adults. The purpose of this study was to determine the time course of post-HWI hypotension and test the hypothesis that a single HWI reduces subsequent 24 h ambulatory blood pressure (ABP) in healthy adults. In a randomized, crossover design, 23 participants [7 female and 16 male; 26 (4) years of age] underwent blood pressure assessments before, during, immediately after and for 24 h following 60 min of immersion in 40.4°C hot water (HWI) and a thermoneutral (24.7°C) air control (CON). Thermal and cardiovascular variables were assessed during and for 60 min after the intervention, after which the participants were instrumented with an ABP monitor for 24 h. At min 60 of the interventions, body core temperature was higher [CON, 36.93 (0.28)°C; HWI, 38.83 (0.19)°C; P < 0.001] and diastolic (P < 0.001) and mean (P < 0.001) arterial blood pressure lower in HWI than CON. HWI increased the diastolic blood pressure nocturnal dip compared with CON [CON, 15.4 (7.2)%; HWI, 19.1 (7.4)%; P = 0.022]. No differences in ABP were observed for 24 h, daytime or nighttime systolic, diastolic or mean arterial blood pressures (all P > 0.05). In conclusion, HWI transiently decreased mean arterial blood pressure and diastolic blood pressure for ≤20 min post-heating and increased the subsequent nocturnal diastolic blood pressure dip in healthy adults.

Sympathetic nervous system activation is a hallmark of high-altitude hypoxia, yet the afferent mechanisms remain incompletely defined. We examined the relative contributions of pulmonary arterial mechanoreceptors and carotid chemoreceptors - two excitatory pathways co-activated by hypoxia - to sustained sympathoexcitation at altitude. Nine healthy lowlanders (27 ±  7 years, three female) were studied after 6-9 days at 3800 m under four conditions: (1) control, (2) inhaled nitric oxide (iNO, 40 ppm) to reduce pulmonary arterial pressure, (3) low-dose dopamine infusion (2 µg kg- 1 min- 1) to suppress the carotid chemoreflex, and (4) combined iNO and dopamine. End-tidal oxygen and carbon dioxide were kept constant throughout. We assessed muscle sympathetic nerve activity (MSNA), systemic haemodynamics, ventilation and pulmonary arterial systolic pressure. iNO reduced pulmonary arterial pressure and significantly decreased MSNA (condition 1: 25 ± 8 bursts min-1 vs. condition 2: 21 ± 7 bursts min-1; P = 0.0415), whereas dopamine infusion reduced ventilation (P < 0.001) without a consistent effect on MSNA (condition 1: 25 ± 8 bursts min-1 vs. condition 3: 28 ± 13 bursts min-1; P = 0.112). Combined intervention produced a small reduction in sympathetic nerve activity (condition 3: 28 ± 13 bursts min-1 vs. condition 4: 26 ± 13 bursts min-1; P = 0.0643), likely due to baroreflex engagement. These findings confirm that unloading pulmonary arterial pressure attenuates MSNA, reinforcing the role of pulmonary mechanoreceptors in high altitude sympathoexcitation. Attempts to isolate a carotid chemoreflex contribution were likely confounded by dopamine's haemodynamic effect, which introduced variability and limited the specificity of this intervention. Thus, interpretation of this component remains exploratory, highlighting the integrative complexity of reflex control of high altitude sympathoexcitation in humans.

The vascular sympathetic baroreflex is critical for stabilising blood pressure. A notable feature of this reflex is hysteresis, a directional asymmetry in responsiveness during rising versus falling pressure that is evident in young adults but attenuated in older age. Whether age-related reduction reflects altered mechanical transduction at baroreceptors or changes in neural processing remains unclear. We compared the mechanical and neural components of the sympathetic baroreflex, with specific focus on hysteresis, in healthy young (21-30 years old, n = 20) and middle-aged (50-63 years, n = 14) males. Continuous recordings of arterial pressure (photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography) and common carotid artery diameter (ultrasound) were obtained during 6 min of supine rest. Spontaneous baroreflex gain was quantified for mechanical (diastolic pressure into carotid diameter) and neural (carotid diameter into MSNA) components, and overall (diastolic pressure into MSNA), with rising and falling pressure sequences analysed separately. Young men exhibited clear hysteresis in the overall baroreflex loop, whereas this was absent in middle-aged men. Mechanical hysteresis was not observed in either age group. In contrast, young men displayed pronounced neural hysteresis (Falling: -0.302 ± 0.157 vs. Rising: -0.128 ± 0.88% bursts µm-1, P < 0.001; g = 1.37), whereas neural hysteresis was absent in middle-aged men (Falling: -0.345 ± 0.400 vs. Rising: -0.396 ± 0.368% burst µm-1, P = 0.348, g = 0.13). These findings suggest that age-related loss of spontaneous sympathetic baroreflex hysteresis is more apparent within the neural rather than the mechanical component.

Elevated muscle sympathetic nerve activity (MSNA) at high altitude is associated with blunted transduction of sympathetic signals to blood pressure in lowlanders and indigenous Andean highlanders. However, it is unclear whether this is due to reduced adrenergic communication or other factors (e.g., augmented dilatory signaling). Therefore, we quantified the contribution of α-adrenoreceptor activity to 1) resting systemic sympathetic transduction and 2) pressor responses to sympathoexcitation in acclimatizing lowlanders (9 M and 4 F) and Andean highlanders (15 M) at 4,300 m. MSNA (microneurography) and mean arterial pressure (MAP; finger photoplethysmography) were measured at rest, during maximal voluntary apnea, and with an α1-adrenergic agonist (phenylephrine) before and following partial α-adrenergic blockade (phentolamine). Sympathetic transduction was quantified as the slope of the relationship between MAP and total MSNA associated with sequences of sympathetic bursts. Transduction was attenuated in both lowlanders (0.0041 ± 0.0037 to 0.0017 ± 0.0017 mmHg·%-1, P = 0.026) and highlanders (0.0033 ± 0.0024 to 0.0008 ± 0.0007 mmHg·%-1, P = 0.005) under α-adrenergic blockade (main effect P < 0.001) and was not different between groups (main effect P = 0.276). However, pressor responses to apnea (lowlanders, +25 ± 5 mmHg and highlanders, +22 ± 7 mmHg) were unchanged following phentolamine (lowlanders, +25 ± 8 mmHg and highlanders, +20 ± 8 mmHg; main effect P = 0.174) despite unchanged MSNA responses between conditions (main effect P = 0.162). Highlanders exhibited reduced MSNA responses compared with lowlanders regardless of condition (main effect P = 0.014). Partial α-adrenergic blockade reduced sympathetic transduction similarly in both groups. Yet, apnea responsiveness was maintained, achieved through lesser sympathoexcitation in highlanders. This suggests that resting blood pressure control is modulated primarily through α-adrenergic receptors in both populations, but pressor responses to stress may result from alternative mechanisms.NEW & NOTEWORTHY 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.

High-altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) via activation of the arterial chemoreflex, pulmonary arterial baroreceptors and resetting of the sympathetic vascular baroreflex. However attempting to silence these mechanisms only partially normalises MSNA, implicating other contributory mechanisms. Increased oxidant production may modulate central sympathetic outflow, while potentially modifying chemosensitivity and vasomotor signalling to the peripheral and pulmonary vasculature. Therefore we tested the hypothesis that blunting oxidative stress would reduce MSNA at high altitude. MSNA (microneurography of the peroneal nerve), continuous arterial pressure (photoplethysmography), vascular tone (duplex ultrasound of the brachial artery), pulmonary artery systolic pressure (PASP, echocardiography) and carotid body tonic activity (1-min hyperoxia) were measured pre- and post-ascorbic acid infusion (200 mg/min for 15-min and then 40 mg/min) in healthy lowlanders (n = 15) after 3-7 days of high-altitude exposure (3800 m). Ascorbic acid infusion improved the redox environment, determined by an increase in whole cell nuclear factor erythroid 2-related factor 2 activity (P = 0.005). Post-infusion MSNA burst frequency (-2 ± 2 bursts/min, P = 0.007) and incidence (-5 ± 4 bursts/100 heartbeats (HB), P = 0.006) decreased. However the infusion increased mean arterial (9 ± 4 mmHg, P≤0.001), systolic (11 ± 8 mmHg, P ≤ 0.004) and diastolic pressure (7 ± 4 mmHg, P ≤ 0.001) and total peripheral resistance (P = 0.013) concomitantly with a reduction in brachial diameter (-0.12 ± 0.14 mm, P = 0.002). Carotid body tonic activity (P = 0.247) and PASP (P = 0.365) remained unchanged by ascorbic acid infusion. In conclusion improving the antioxidant environment lowered MSNA at high altitude; however the small reduction is likely a consequence of the increased blood pressure secondary to the blunting of hypoxic vasodilation rather than a direct effect on sympathetic outflow. KEY POINTS: High-altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) from sea level values. Pulmonary artery systolic pressure (PASP), peripheral arterial chemoreflex and high altitude-induced hypovolaemia are involved in the increase in MSNA; however current evidence indicates additional contributory mechanisms. Hypoxia associated with high altitude results in an increase in the production of reactive oxygen species (ROS), which may be sympathoexcitatory. Therefore we tested the hypothesis that improving the redox environment using an ascorbic acid infusion would lower sympathetic nerve activity. After the infusion, sympathetic nerve activity was reduced alongside an increase in vascular tone and elevation in blood pressure. The reduction in MSNA occurred independently of changes in PASP and chemoreflex activity. Our findings demonstrate that ROS elevates sympathetic nerve activity at high altitude; however this reduction is likely a result of the elevated blood pressure after the blunting of hypoxic vasodilation.

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 (FiO2 = 12.5%) to elevate pulmonary artery pressure (PAP) above normal, whilst MSNA (microneurography), systemic blood pressure (photoplethysmography, BP), oxygen saturation (SpO2) and minute ventilation (VE) 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 VE 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. 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.

To test the hypothesis that hot water immersion (HWI) improves cerebrovascular function via shear-mediated mechanisms, this study determined cerebrovascular reactivity to carbon dioxide ( CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_2}}}$ ) before and after 60 min of 39°C HWI and a 21°C air control (CON) in 15 healthy participants. Thermal and haemodynamic variables were assessed throughout the trials, and CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_2}}}$ was determined by a 4-min inhalation of hypercapnic gas (6% CO2, 21% O2, N2 balance) and the assessment of internal carotid artery (ICA) blood flow by duplex ultrasound before and 45 min after HWI and CON. At 60 min of the interventions, core body temperature (CON, 36.9 ± 0.3°C; HWI, 38.1 ± 0.3°C, P < 0.01), heart rate (P < 0.01) and ICA conductance (P < 0.01) were higher in HWI than CON, while, mean arterial blood pressure was lower (CON, 82 ± 9 mmHg; HWI 65 ± 8 mmHg, P < 0.01). No differences were observed for ICA diameter, ICA blood velocity, ICA shear rate and ICA blood flow between HWI and CON (all P > 0.05). ICA CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_2}}}$ did not change after either CON (pre: 13.9 ± 9.2 to post: 11.3 ± 6.1 mL min-1 mmHg-1) or HWI (pre: 14.6 ± 7.9 to post: 10.9 ± 5.4 mL min-1 mmHg-1; Interaction P = 0.65). In conclusion, HWI reduced blood pressure and increased ICA conductance (i.e. autoregulation) to maintain blood flow to the brain; however, HWI did not influence subsequent cerebrovascular function, as assessed by CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ .

Sympathoexcitation is a hallmark of hypoxic exposure, occurring acutely, as well as persisting in acclimatised lowland populations and with generational exposure in highland native populations of the Andean and Tibetan plateaus. The mechanisms mediating altitude sympathoexcitation are multifactorial, involving alterations in both peripheral autonomic reflexes and central neural pathways, and are dependent on the duration of exposure. Initially, hypoxia-induced sympathoexcitation appears to be an adaptive response, primarily mediated by regulatory reflex mechanisms concerned with preserving systemic and cerebral tissue O 2 delivery and maintaining arterial blood pressure. However, as exposure continues, sympathoexcitation is further augmented above that observed with acute exposure, despite acclimatisation processes that restore arterial oxygen content ( C a O 2 ${C_{{\mathrm{a}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Under these conditions, sympathoexcitation may become maladaptive, giving rise to reduced vascular reactivity and mildly elevated blood pressure. Importantly, current evidence indicates the peripheral chemoreflex does not play a significant role in the augmentation of sympathoexcitation during altitude acclimatisation, although methodological limitations may underestimate its true contribution. Instead, processes that provide no obvious survival benefit in hypoxia appear to contribute, including elevated pulmonary arterial pressure. Nocturnal periodic breathing is also a potential mechanism contributing to altitude sympathoexcitation, although experimental studies are required. Despite recent advancements within the field, several areas remain unexplored, including the mechanisms responsible for the apparent normalisation of muscle sympathetic nerve activity during intermediate hypoxic exposures, the mechanisms accounting for persistent sympathoexcitation following descent from altitude and consideration of whether there are sex-based differences in sympathetic regulation at altitude.

This review considers interoceptive signalling from the heart and coronary circulation. Vagal and cardiac sympathetic afferent sensory nerve endings are distributed throughout the atria, ventricles (mainly left), and coronary artery. A small proportion of cardiac receptors attached to thick myelinated vagal afferents are tonically active during the cardiac cycle. Dependent upon location, these mechanoreceptors detect fluctuations in atrial volume and coronary arterial perfusion. Atrial volume and coronary arterial signals contribute to beat-to-beat feedback control and physiological homeostasis. Most cardiac receptors are attached to thinly myelinated or nonmyelinated C fibres, many of which are unresponsive to the cardiac cycle. Of these, there are many chemically sensitive cardiac receptors which are activated during myocardial stress by locally released endogenous substances. In contrast, some tonically inactive receptors become activated by irregular ventricular wall mechanics or by distortion of the ischaemic myocardium. Furthermore, some are excited both by chemical mediators of ischaemia and wall abnormalities. Reflex responses arising from cardiac receptors attached to thinly myelinated or nonmyelinated are complex. Impulses that project centrally through vagal afferents elicit sympathoinhibition and hypotension, whereas impulses travelling in cardiac sympathetic afferents and spinal pathways elicit sympathoexcitation and hypertension. Two opposing cardiac reflexes may provide a mechanism for fine-tuning a composite haemodynamic response during myocardial stress. Sympathetic afferents provide the primary pathway for transmission of cardiac nociception to the central nervous system. However, activation of sympathetic afferents may increase susceptibility to life-threatening arrhythmias. Notably, the cardiac sympathetic afferent reflex predominates in pathophysiological states including hypertension and heart failure.

The impact of posture and sex on cardiovascular control during rhythmic handgrip (RHG) exercise is unknown. We show that increases in muscle sympathetic nerve activity (MSNA) during RHG are partly mediated by a reduction in sympathetic baroreflex gain. In addition, males demonstrate larger increases in total MSNA during upright RHG than females. These data indicate that the baroreflex partly mediates increases in MSNA during RHG and that males have a greater sympathetic vasoconstrictor reserve than females.

Objectives We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19.Study design Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date.Intervention Short exercise tests.Primary outcome measures Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability.Results Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19.Conclusions Further research is needed to aid clinical decision-making at discharge from hospital.

Central arterial stiffness can influence exercise blood pressure (BP) by increasing the rise in arterial pressure per unit increase in aortic inflow. Whether central arterial stiffness influences the pressor response to isometric handgrip exercise (HG) and post-exercise muscle ischemia (PEMI), two common laboratory tests to study sympathetic control of BP, is unknown. We studied 46 healthy non-hypertensive males (23 young and 23 middle-aged) during HG (which increases in cardiac output [Q̇c]) and isolated metaboreflex activation PEMI (no change or decreases in Q̇c). Aortic stiffness (aortic pulse wave velocity [aPWV]; applanation tonometry via SphygmoCor) was measured during supine rest and was correlated to the pressor responses to HG and PEMI. BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA) were continuously recorded at rest, during HG to fatigue (35 % maximal voluntary contraction) and 2-min of PEMI. aPWV was higher in middle-aged compared to young males (7.1 ± 0.9 vs 5.4 ± 0.7 m/s, P < 0.001). Middle-aged males also exhibited greater increases in systolic pressure (∆30 ± 11 vs 10 ± 8 mmHg) and MSNA (∆2313 ± 2006 vs 1387 ± 1482 %/min) compared to young males during HG (both, P < 0.03); with no difference in the Q̇c response (P = 0.090). Responses to PEMI were not different between groups. Sympathetic transduction during these stressors (MSNA-diastolic pressure slope) was not different between groups (P > 0.341). Middle-aged males displayed a greater increase in SBP per unit change of Q̇c during HG (∆SBP/∆Q̇c; 21 ± 18 vs 6 ± 10 mmHg/L/min, P = 0.004), with a strong and moderate relationship between the change in systolic (r = 0.53, P < 0.001) and diastolic pressure (r = 0.34, P = 0.023) and resting aPWV, respectively; with no correlation during PEMI. Central arterial stiffness can modulate pressor responses during stimuli associated with increases in cardiac output and sympathoexcitation in healthy males.

Abstract An age‐associated increase in arterial blood pressure is evident for apparently healthy humans. This is frequently attributed to stiffening of the central arteries and a concurrent increase in sympathetic outflow, potentially mediated by a reduced ability of the baroreceptive vessels to distend. This is supported, in part, by a reduced mechanical component of the vascular sympathetic baroreflex (i.e., a reduction in distension for a given pressure). Previous characterization of the mechanical component has assessed only carotid artery distension; however, evidence suggests that both the aortic and carotid baroreflexes are integral to blood pressure regulation. In addition, given that baroreceptors are located in the vessel wall, the change in wall tension, comprising diameter, pressure and vessel wall thickness, and the mechanics of this change might provide a better index of the baroreceptor stimulus than the previous method used to characterize the mechanical component that relies on diameter alone. This brief review summarizes the data using this new method of assessing barosensory vessel mechanics and their influence on the vascular sympathetic baroreflex across the lifespan.

Desaturation on exercise has been suggested as a predictive feature for deterioration in COVID-19. The objective of this paper was to determine the feasibility and validity for the 40-steps desaturation test.A prospective observational cohort study was undertaken in patients assessed in hospital prior to discharge. One-hundred and fifty-two participants were screened between November 2020 and February 2021, and 64 were recruited to perform a 40-steps desaturation test. Patients who were able to perform the test were younger and less frail. Four patients were readmitted to hospital and one patient deteriorated within 30 days but no patient died. The majority of patients showed little change in saturations during the test, even with pre-existing respiratory pathology. Change in saturations, respiratory rate, heart rate and breathlessness were not predictive of death or readmission to hospital within 30 days. Of 13 patients who had a desaturation of 3% or more during exercise, none was readmitted to hospital within 30 days. Not enough patients with COVID-19 could be recruited to the study to provide evidence for the safety of the test in this patient group. The 40-steps desaturation test requires further evaluation to assess clinical utility.

Distinct populations of stretch-sensitive mechanoreceptors attached to myelinated vagal afferents are found in the heart and adjoining coronary and pulmonary circulations. Receptors at atrio venous junctions appear to be involved in control of intravascular volume. These atrial receptors influence sympathetic control of the heart and kidney, but contribute little to reflex control of systemic vascular resistance. Baroreceptors at the origins of the coronary circulation elicit reflex vasodilatation, like feedback control from systemic arterial baroreceptors, as well as having characteristics that could contribute to regulation of mean pressure. In contrast, feedback from baroreceptors in the pulmonary artery and bifurcation is excitatory and elicits a pressor response. Elevation of pulmonary arterial pressure resets the vasomotor limb of the systemic arterial baroreflex, which could be relevant for control of sympathetic vasoconstrictor outflow during exercise and other states associated with elevated pulmonary arterial pressure. Ventricular receptors, situated mainly in the inferior posterior wall of the left ventricle, and attached to unmyelinated vagal afferents, are relatively inactive under basal conditions. However, a change to the biochemical environment of cardiac tissue surrounding these receptors elicits a depressor response. Some ventricular receptors respond, modestly, to mechanical distortion. Probably, ventricular receptors contribute little to tonic feedback control; however, reflex bradycardia and hypotension in response to chemical activation may decrease the work of the heart during myocardial ischaemia. Overall, greater awareness of heterogeneous reflex effects originating from cardiac, coronary and pulmonary artery mechanoreceptors is required for a better understanding of integrated neural control of circulatory function and arterial blood pressure.w

We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men. Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively. Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604). There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men.

Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.

Developing an exercise model that resembles a traditional form of aerobic exercise and facilitates a complete simultaneous assessment of multiple parameters within the oxygen cascade is critically for understanding exercise intolerances in diseased populations. Measurement of muscle blood flow is a crucial component of such a model and previous studies have used invasive procedures to determine blood flow kinetics; however, this may not be appropriate in certain populations. Furthermore, current models utilizing Doppler ultrasound use isolated limb exercise and while these studies have provided useful data, the exercise model does not mimic the whole‐body physiological response to continuous dynamic exercise. Therefore, we aimed to measure common femoral artery blood flow using Doppler ultrasound during continuous dynamic stepping exercise performed at three independent workloads to assess the within day and between‐day reliability for such an exercise modality. We report a within‐session coefficient of variation of 5.8% from three combined workloads and a between‐day coefficient of variation of 12.7%. These values demonstrate acceptable measurement accuracy and support our intention of utilizing this noninvasive exercise model for an integrative assessment of the whole‐body physiological response to exercise in a range of populations.