Creating your own line: reflections from early career scientists.

The changing landscape of academia can be difficult to navigate for anyone at any point throughout their career. One thing is certainly clear: effective mentorship is key to ensuring success, fueling scientific curiosity, and creating a sense of community. This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees; it is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.NEW & NOTEWORTHY This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees that is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.

Inhaled nitric oxide does not improve maximal oxygen consumption in endurance trained and untrained healthy individuals.

PURPOSE: Previous work suggests that endurance-trained athletes have superior pulmonary vasculature function as compared to untrained individuals, which may contribute to their greater maximal oxygen uptake ([Formula: see text]O2max). Inhaled nitric oxide (iNO) reduces pulmonary vascular resistance in healthy individuals, which could translate into greater cardiac output and improved [Formula: see text]O2max, particularly in untrained individuals. The purpose of the study was to examine whether iNO improved [Formula: see text]O2max in endurance trained and untrained individuals. METHODS: Sixteen endurance-trained and sixteen untrained individuals with normal lung function completed this randomized double-blind cross-over study over four sessions. Experimental cardiopulmonary exercise tests were completed while breathing either normoxia (placebo) or 40 ppm of iNO, on separate days (order randomized). On an additional day, echocardiography was used to determine pulmonary artery systolic pressure at rest and during sub-maximal exercise (60 Watts) while participants breathed normoxia or iNO. RESULTS: Right ventricular systolic pressure was significantly reduced by iNO during exercise (Placebo: 34 ± 7 vs. iNO: 32 ± 7; p = 0.04). [Formula: see text]O2max was greater in the endurance trained group (Untrained: 3.1 ± 0.7 vs. Endurance: 4.3 ± 0.9 L min-1; p < 0.01), however, there was no effect of condition (p = 0.79) and no group by condition interaction (p = 0.68). Peak cardiac output was also unchanged by iNO in either group. CONCLUSION: Despite a reduction in right ventricular systolic pressure, the lack of change in [Formula: see text]O2max with iNO suggests that the pulmonary vasculature does not limit [Formula: see text]O2max in young healthy individuals, regardless of fitness level.

HIIT'ing or MISS'ing the Optimal Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of High- Versus Moderate-Intensity Exercise Prescription.

Introduction: Polycystic Ovary syndrome (PCOS) is a metabolic disorder associated with increased cardiovascular disease risk. Exercise is an effective treatment strategy to manage symptoms and reduce long-term health risk. High-intensity interval training (HIIT) has been suggested as a more efficient exercise mode in PCOS; however, it is not clear whether HIIT is superior to moderate intensity steady state exercise (MISS). Methods: We synthesized available data through a systematic review and meta-analysis to compare the effectiveness of isolated HIIT and MISS exercise interventions. Our primary outcome measures were cardiorespiratory fitness and insulin resistance, measured using V ˙ O2max and HOMA-IR respectively. Results: A total of 16 studies were included. Moderate-quality evidence from 16 studies identified significant improvements in V ˙ O2max following MISS (Δ = 1.081 ml/kg/min, p < 0.001, n = 194), but not HIIT (Δ = 0.641 ml/kg/min, p = 0.128, n = 28). Neither HIIT nor MISS improved HOMA-IR [(Δ = -0.257, p = 0.374, n = 60) and (Δ = -0.341, p = 0.078, n = 159), respectively]. Discussion: A significant improvement in V ˙ O2max was evident following MISS, but not HIIT exercise in women with PCOS. This contrasts with previous literature in healthy and clinical cohorts that report superior benefits of HIIT. Therefore, based on available moderate-quality evidence, HIIT exercise does not provide superior outcomes in V ˙ O2max compared with MISS, although larger high-quality interventions are needed to fully address this. Additional dietary/pharmacological interventions may be required in conjunction with exercise to improve insulin sensitivity.

Global REACH 2018: volume regulation in high-altitude Andeans with and without chronic mountain sickness.

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed NH2-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP) in Andean males without (n = 14; age = 39 ± 11 yr) and with (n = 10; age = 40 ± 12 yr) CMS at 4,330 m (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8 ± 7.9 ng/mL vs. CMS: 8.7 ± 5.4 ng/mL; P = 0.025) and plasma aldosterone concentration (non-CMS: 77.5 ± 35.5 pg/mL vs. CMS: 54.2 ± 28.9 pg/mL; P = 0.018) were lower in highlanders with CMS compared with non-CMS, whereas NT pro-BNP was not different between groups (non-CMS: 1394.9 ± 214.3 pg/mL vs. CMS: 1451.1 ± 327.8 pg/mL; P = 0.15). Highlanders had similar total blood volume (non-CMS: 90 ± 15 mL·kg-1 vs. CMS: 103 ± 18 mL·kg-1; P = 0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46 ± 10 mL·kg-1 vs. CMS: 66 ± 14 mL·kg-1; P < 0.01) and smaller plasma volume (non-CMS: 43 ± 7 mL·kg-1 vs. CMS: 35 ± 5 mL·kg-1; P = 0.03) compared with non-CMS. There were no differences in ePASP between groups (non-CMS: 32 ± 9 mmHg vs. CMS: 31 ± 8 mmHg; P = 0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r = -0.66; P < 0.01; non-CMS: r = -0.60; P = 0.022; CMS: r = -0.63; P = 0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high altitude, causing potentially greater polycythemia and clinical symptoms.

Right Ventricular Function and Region-Specific Adaptation in Athletes Engaged in High-Dynamic Sports: A Meta-Analysis.

BACKGROUND: Structural remodeling of the right ventricle (RV) is widely documented in athletes. However, functional adaptation, including RV pressure generation and systolic free-wall longitudinal mechanics, remains equivocal. This meta-analysis compared RV pressure and function in athletes and controls. METHODS: A systematic review of online databases was conducted up to June 4, 2020. Meta-analyses were performed on RV systolic pressures, at rest and during exercise, tricuspid annular plane systolic displacement, myocardial velocity (S'), and global and regional longitudinal strain. Bias was assessed using Egger regression for asymmetry. Data were analyzed using random-effects models with weighted mean difference and 95% CI. RESULTS: Fifty-three studies were eligible for inclusion. RV systolic pressure was obtained from 21 studies at rest (n=1043:1651; controls:athletes) and 8 studies during exercise (n=240:495) and was significantly greater in athletes at rest (weighted mean difference, 2.9 mmHg [CI, 1.3-4.5 mmHg]; P=0.0005) and during exercise (11.0 [6.5-15.6 mm Hg]; P<0.0001) versus controls. Resting tricuspid annular plane systolic displacement (P<0.0001) and S' (P=0.001) were greater in athletes. In contrast, athletes had similar RV free-wall longitudinal strain (17 studies; n=450:605), compared with controls but showed greater longitudinal apical strain (16 studies; n=455:669; 0.9%, 0.1%-1.8%; P=0.03) and lower basal strain (-2.5% [-1.4 to -3.5%]; P<0.0001). CONCLUSIONS: Functional RV adaptation, characterized by increased tricuspid annular displacement and velocity and a greater base-to-apex strain gradient, is a normal feature of the athlete's heart, together with a slightly elevated RV systolic pressure. These findings contribute to our understanding of RV in athletes and highlight the importance of considering RV function in combination with structure in the clinical interpretation of the athlete's heart.

Physical Activity Behaviors and Barriers in Multifetal Pregnancy: What to Expect When You're Expecting More.

The health benefits of prenatal physical activity (PA) are established for singleton pregnancies. In contrast, individuals with multifetal pregnancies (twins, triplets or more) are recommended to restrict or cease PA. The objectives of the current study were to determine behaviors and barriers to PA in multifetal pregnancies. Between 29 May and 24 July 2020, individuals with multifetal pregnancies participated in an online survey. Of the 415 respondents, there were 366 (88%) twin, 45 (11%) triplet and 4 (1%) quadruplet pregnancies. Twenty-seven percent (n = 104/388) of respondents completed no PA at all during pregnancy, 57% (n = 220/388) completed PA below current recommendations, and 16% (n = 64/388) achieved current recommendations (150-min per week of moderate-intensity activity). Most respondents (n = 314/363 [87%]) perceived barriers to PA during multifetal pregnancy. The most prominent were physical symptoms (n = 204/363 [56%]) and concerns about risks to fetal wellbeing (n = 128/363 [35%]). Sixty percent (n = 92/153) felt that these barriers could be overcome but expressed the need for evidence-based information regarding PA in multifetal pregnancy. Individuals with multifetal pregnancies have low engagement with current PA recommendations but remain physically active in some capacity. There are physical and psychosocial barriers to PA in multifetal pregnancy and future research should focus on how these can be removed.

Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: A randomized-control cross-over trial.

KEY POINTS: Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO2 production ( V̇E / V̇CO2 ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on V̇E / V̇CO2 , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced V̇E / V̇CO2 and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD. ABSTRACT: Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO2 production ( V̇E / V̇CO2 ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower V̇E / V̇CO2 and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized-control cross-over study, 15 patients with mild COPD (FEV1  =  89 ± 11% predicted) and 15 healthy controls completed symptom-limited cardiopulmonary exercise tests while breathing normoxic gas or 40 ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80 ± 0.14 vs. 1.53 ± 0.10 L·min-1 , P < 0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60 W, iNO reduced V̇E / V̇CO2 by 3.8 ± 4.2 units (P = 0.002) and dyspnoea by 1.1 ± 1.2 Borg units (P < 0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced V̇E / V̇CO2 and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased V̇E / V̇CO2 , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.

Cardiovascular function during triplet pregnancy.

Pregnancy is recognized as a natural physiological stressor to the maternal cardiovascular system. Cardiovascular adaptation is markedly greater in twin pregnancy compared with singleton pregnancy; however, these changes are sparsely documented in triplet pregnancy. The aim of this case series was to compare maternal cardiac function, cardioautonomic regulation, and blood pressure reactivity in healthy singleton, twin, and triplet pregnancies. Resting cardiac structure and function (echocardiography), beat-by-beat blood pressure variability (BPV; photoplethysmography), and heart rate variability (HRV; electrocardiogram) were measured in two triplet, three twin, and three singleton pregnancies (matched for maternal age, prepregnancy body mass index, and gestational age). Hemodynamic responses to a 3-min cold pressor test were also recorded to assess blood pressure reactivity. Due to the small sample size of this case series, statistical comparisons were not made between groups. Compared with singleton and twin pregnancies, individuals pregnant with triplets had greater resting cardiac output but lower cardiac deformation (longitudinal strain, basal circumferential strain, and torsion), sympathetic dominance in cardioautonomic regulation (lower HRV and higher BPV), and elevated blood pressure reactivity in response to the cold pressor test. Taken together, these observations suggest that females with triplet pregnancies may have reduced cardiovascular function, which may contribute to the heightened risk of complications in multifetal pregnancies.NEW & NOTEWORTHY Individuals with healthy triplet pregnancies had greater resting cardiac output but lower left ventricular mechanics when compared with singleton and twin pregnancies matched for gestational age. In addition, triplet pregnancies had greater blood pressure variability and lower overall heart rate variability compared with singleton pregnancies, as well as greater blood pressure reactivity to the cold pressor test. Healthy triplet pregnancies may have reduced cardiovascular function as well as a greater sympathetic contribution to cardiac control.

Cardiac Responses to Prenatal Resistance Exercise with and without the Valsalva Maneuver.

PURPOSE: Exercise guidelines recommend incorporating resistance exercise (RE) into a regular aerobic training program during pregnancy. However, few women do so because of uncertainties about the safety of prenatal RE, particularly regarding the Valsalva maneuver (VM). The aim of this study was to determine the acute cardiovascular responses to prenatal RE at different intensities, with and without VM. METHODS: Healthy pregnant (n = 15; 22.9 ± 5.9 wk of gestation) and nonpregnant women (n = 15) were recruited. Maximal strength over 10 repetitions (10RM) for semireclined leg press was determined. Women underwent standardized assessments of cardiac structure, function and mechanics (echocardiography), heart rate (ECG), and blood pressure (photoplethysmography) at baseline, during RE at 20%, 40%, and 60% 10RM while free-breathing, and at 40% 10RM with VM. Significant differences were identified between subjects at baseline (independent t-tests), between and within subjects during free-breathing RE (general linear model, baseline as a covariate), and between and within subjects for 40% 10RM free-breathing versus VM (mixed-effects model). RESULTS: Resting cardiac output, heart rate, and stroke volume were greater in pregnant women, without differences in blood pressure, ejection fraction, or cardiac mechanics. During free-breathing RE, pregnant women had a greater ejection fraction compared with nonpregnant women; however, all other hemodynamic variables were not different between groups. Cardiac mechanics during free-breathing RE across all intensities were not different between groups, with the exception that pregnant women had a lower apical circumferential strain that did not affect global cardiac function. No differences were observed between groups during 40% 10RM RE with and without VM. CONCLUSIONS: Pregnant women have proportionate cardiac responses to light-moderate RE, both with and without the VM. These findings reinforce the safety of RE in healthy pregnancy.

The 2018 Global Research Expedition on Altitude Related Chronic Health (Global REACH) to Cerro de Pasco, Peru: an Experimental Overview.

NEW FINDINGS: What is the central question of this study? Herein, a methodological overview of our research team's (Global REACH) latest high altitude research expedition to Peru is provided. What is the main finding and its importance? The experimental objectives, expedition organization, measurements and key cohort data are discussed. The select data presented in this manuscript demonstrate the haematological differences between lowlanders and Andeans with and without excessive erythrocytosis. The data also demonstrate that exercise capacity was similar between study groups at high altitude. The forthcoming findings from our research expedition will contribute to our understanding of lowlander and indigenous highlander high altitude adaptation. ABSTRACT: In 2016, the international research team Global Research Expedition on Altitude Related Chronic Health (Global REACH) was established and executed a high altitude research expedition to Nepal. The team consists of ∼45 students, principal investigators and physicians with the common objective of conducting experiments focused on high altitude adaptation in lowlanders and in highlanders with lifelong exposure to high altitude. In 2018, Global REACH travelled to Peru, where we performed a series of experiments in the Andean highlanders. The experimental objectives, organization and characteristics, and key cohort data from Global REACH's latest research expedition are outlined herein. Fifteen major studies are described that aimed to elucidate the physiological differences in high altitude acclimatization between lowlanders (n = 30) and Andean-born highlanders with (n = 22) and without (n = 45) excessive erythrocytosis. After baseline testing in Kelowna, BC, Canada (344 m), Global REACH travelled to Lima, Peru (∼80 m) and then ascended by automobile to Cerro de Pasco, Peru (∼4300 m), where experiments were conducted over 25 days. The core studies focused on elucidating the mechanism(s) governing cerebral and peripheral vascular function, cardiopulmonary regulation, exercise performance and autonomic control. Despite encountering serious logistical challenges, each of the proposed studies was completed at both sea level and high altitude, amounting to ∼780 study sessions and >3000 h of experimental testing. Participant demographics and data relating to acid-base balance and exercise capacity are presented. The collective findings will contribute to our understanding of how lowlanders and Andean highlanders have adapted under high altitude stress.

Global REACH 2018: Andean highlanders, chronic mountain sickness and the integrative regulation of resting blood pressure.

NEW FINDINGS: What is the central question of this study? Does chronic mountain sickness (CMS) alter sympathetic neural control and arterial baroreflex regulation of blood pressure in Andean (Quechua) highlanders? What is the main finding and its importance? Compared to healthy Andean highlanders, basal sympathetic vasomotor outflow is lower, baroreflex control of muscle sympathetic nerve activity is similar, supine heart rate is lower and cardiovagal baroreflex gain is greater in mild CMS. Taken together, these findings reflect flexibility in integrative regulation of blood pressure that may be important when blood viscosity and blood volume are elevated in CMS. ABSTRACT: The high-altitude maladaptation syndrome chronic mountain sickness (CMS) is characterized by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, during the 2018 Global REACH expedition to Cerro de Pasco, Peru (4383 m), we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in eight Andean natives with CMS ([Hb] 22.6 ± 0.9 g·dL-1 ) and seven healthy highlanders ([Hb] 19.3 ± 0.8 g·dL-1 ). R-R interval (RRI, electrocardiogram), beat-by-beat BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest and during pharmacologically induced changes in BP (modified Oxford test). Although [Hb] and blood viscosity (7.8 ± 0.7 vs. 6.6 ± 0.7 cP; d = 1.7, P = 0.01) were elevated in CMS compared to healthy highlanders, cardiac output, total peripheral resistance and mean BP were similar between groups. The vascular sympathetic baroreflex MSNA set-point (i.e. MSNA burst incidence) and reflex gain (i.e. responsiveness) were also similar between groups (MSNA set-point, d = 0.75, P = 0.16; gain, d = 0.2, P = 0.69). In contrast, in CMS the cardiovagal baroreflex operated around a longer RRI (960 ± 159 vs. 817 ± 50 ms; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs. 8.8 ± 2.6 ms·mmHg-1 ; d = 1.8, P = 0.01) versus healthy highlanders. Basal sympathetic vasomotor activity was also lower compared to healthy highlanders (33 ± 11 vs. 45 ± 13 bursts·min-1 ; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate compensate for the haemodynamic consequences of excessive erythrocyte volume and contribute to integrative blood pressure regulation in Andean highlanders with mild CMS.

Cardiac Responses to Submaximal Isometric Contraction and Aerobic Exercise in Healthy Pregnancy.

PURPOSE: The increased physiological demand of pregnancy results in the profound adaptation of the maternal cardiovascular system, reflected by greater resting cardiac output and left ventricular (LV) deformation. Whether the increased resting demand alters acute cardiac responses to exercise in healthy pregnant women is not well understood. METHODS: Healthy nonpregnant (n = 18), pregnant (n = 14, 22-26 wk gestation), and postpartum women (n = 13, 12-16 wk postdelivery) underwent assessments of cardiac function and LV mechanics at rest, during a sustained isometric forearm contraction (30% maximum), and during low-intensity (LOW) and moderate-intensity (MOD) dynamic cycling exercise (25% and 50% peak power output). Significant differences (α = 0.05) were determined using ANCOVA and general linear model (resting value included as covariate). RESULTS: When accounting for higher resting cardiac output in pregnant women, pregnant women had greater cardiac output during isometric contraction (2.0 ± 0.3 L·min-1·m-1.83; nonpregnant, 1.3 ± 0.2 L·min-1·m-1.83; postpartum, 1.5 ± 0.5 L·min-1·m-1.83; P = 0.02) but similar values during dynamic cycling exercise (pregnant, LOW = 2.8 ± 0.4 L·min-1·m-1.83, MOD = 3.4 ± 0.7 L·min-1·m-1.83; nonpregnant, LOW = 2.4 ± 0.3 L·min-1·m-1.83, MOD = 3.0 ± 0.3 L·min-1·m-1.83; postpartum, LOW = 2.3 ± 0.4 L·min-1·m-1.83, MOD = 3.0 ± 0.5 L·min-1·m-1.83; P = 0.96). Basal circumferential strain was higher in pregnant women at rest, during the sustained isometric forearm contraction (-23.5% ± 1.2%; nonpregnant, -14.6% ± 1.4%; P = 0.001), and during dynamic cycling exercise (LOW = -27.0% ± 4.9%, MOD = -27.4% ± 4.6%; nonpregnant, LOW = -15.8% ± 4.5%, MOD = -15.2% ± 6.7%; P = 0.012); however, other parameters of LV mechanics were not different between groups. CONCLUSION: The results support that the maternal heart can appropriately respond to additional cardiac demand and altered loading experienced during acute isometric and dynamic exercise, although subtle differences in responses to these challenges were observed. In addition, the LV mechanics that underpin global cardiac function are greater in pregnant women during exercise, leading to the speculation that the hormonal milieu of pregnancy influences regional deformation.

Cardioautonomic control in healthy singleton and twin pregnancies.

In conjunction with significant cardiovascular adaptation, changes in cardioautonomic balance, specifically greater sympathetic activation and vagal withdrawal, are considered normal adaptations to healthy singleton pregnancy. Cardiovascular adaptation to twin pregnancy is more profound than that of singleton pregnancies; however, the changes in cardioautonomic control during multifetal gestation are unknown. To address this gap, beat-by-beat blood pressure (photoplethysmography) and heart rate (lead II electrocardiogram) were measured continuously in 25 twin pregnancies and 25 singleton pregnancies (matched for age, prepregnancy body mass index, and gestational age) during 10 min of rest. Data extracted from a 3- to 5-min period were used to analyze heart rate variability (HRV), blood pressure variability (BPV), cardiovagal baroreflex gain, and cardiac intervals as indicators of cardioautonomic control. Independent t tests were used to determine statistical differences between groups (α = 0.05), and the false rate discovery was determined to adjust for multiple comparisons. Resting heart rate was greater in twin compared with singleton pregnancies (91 ± 10 vs. 81 ± 10 beats/min; P = 0.001), but blood pressure was not different. Individuals with twin pregnancies had lower HRV, evidenced by lower standard deviation of R-R intervals (32 ± 11 vs. 47 ± 18 ms; P = 0.001), total power (1,035 ± 810 vs. 1,945 ± 1,570 ms2; P = 0.004), and high frequency power (224 ± 262 vs. 810 ± 806 ms2; P < 0.001) compared with singleton pregnancies. There were no differences in cardiac intervals, BPV, and cardiovagal baroreflex gain between groups. Our findings suggest that individuals with twin pregnancies have greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control is impacted during twin compared with singleton pregnancy.NEW & NOTEWORTHY Individuals with healthy twin pregnancies had lower overall heart rate variability compared with those with singleton pregnancies at similar gestational ages. These results suggest a greater sympathetic and reduced parasympathetic contribution to cardiac control in twin pregnancies. Baseline heart rate was elevated, while arterial pressure and spontaneous cardiovagal baroreflex gain were not different between groups. This was result of the upward resetting of the cardiovagal baroreflex during healthy twin pregnancy, thus maintaining arterial pressure.

Global REACH 2018: renal oxygen delivery is maintained during early acclimatization to 4,330 m.

Early acclimatization to high altitude is characterized by various respiratory, hematological, and cardiovascular adaptations that serve to restore oxygen delivery to tissue. However, less is understood about renal function and the role of renal oxygen delivery (RDO2) during high altitude acclimatization. We hypothesized that 1) RDO2 would be reduced after 12 h of high altitude exposure (high altitude day 1) but restored to sea level values after 1 wk (high altitude day 7) and 2) RDO2 would be associated with renal reactivity, an index of acid-base compensation at high altitude. Twenty-four healthy lowlander participants were tested at sea level (344 m, Kelowna, BC, Canada) and on day 1 and day 7 at high altitude (4,330 m, Cerro de Pasco, Peru). Cardiac output, renal blood flow, and arterial and venous blood sampling for renin-angiotensin-aldosterone system hormones and NH2-terminal pro-B-type natriuretic peptides were collected at each time point. Renal reactivity was calculated as follows: (Δarterial bicarbonate)/(Δarterial Pco2) between sea level and high altitude day 1 and sea level and high altitude day 7. The main findings were that 1) RDO2 was initially decreased at high altitude compared with sea level (ΔRDO2: -22 ± 17%, P < 0.001) but was restored to sea level values on high altitude day 7 (ΔRDO2: -6 ± 14%, P = 0.36). The observed improvements in RDO2 resulted from both changes in renal blood flow (Δ from high altitude day 1: +12 ± 11%, P = 0.008) and arterial oxygen content (Δ from high altitude day 1: +44.8 ± 17.7%, P = 0.006) and 2) renal reactivity was positively correlated with RDO2 on high altitude day 7 (r = 0.70, P < 0.001) but not high altitude day 1 (r = 0.26, P = 0.29). These findings characterize the temporal responses of renal function during early high altitude acclimatization and the influence of RDO2 in the regulation of acid-base balance.

Highs and lows of sympathetic neurocardiovascular transduction: influence of altitude acclimatization and adaptation.

High-altitude (>2,500 m) exposure results in increased muscle sympathetic nervous activity (MSNA) in acclimatizing lowlanders. However, little is known about how altitude affects MSNA in indigenous high-altitude populations. Additionally, the relationship between MSNA and blood pressure regulation (i.e., neurovascular transduction) at high-altitude is unclear. We sought to determine 1) how high-altitude effects neurocardiovascular transduction and 2) whether differences exist in neurocardiovascular transduction between low- and high-altitude populations. Measurements of MSNA (microneurography), mean arterial blood pressure (MAP; finger photoplethysmography), and heart rate (electrocardiogram) were collected in 1) lowlanders (n = 14) at low (344 m) and high altitude (5,050 m), 2) Sherpa highlanders (n = 8; 5,050 m), and 3) Andean (with and without excessive erythrocytosis) highlanders (n = 15; 4,300 m). Cardiovascular responses to MSNA burst sequences (i.e., singlet, couplet, triplet, and quadruplet) were quantified using custom software (coded in MATLAB, v.2015b). Slopes were generated for each individual based on peak responses and normalized total MSNA. High altitude reduced neurocardiovascular transduction in lowlanders (MAP slope: high altitude, 0.0075 ± 0.0060 vs. low altitude, 0.0134 ± 0.080; P = 0.03). Transduction was elevated in Sherpa (MAP slope, 0.012 ± 0.007) compared with Andeans (0.003 ± 0.002, P = 0.001). MAP transduction was not statistically different between acclimatizing lowlanders and Sherpa (MAP slope, P = 0.08) or Andeans (MAP slope, P = 0.07). When resting MSNA is accounted for (ANCOVA), transduction was inversely related to basal MSNA (bursts/minute) independent of population (RRI, r = 0.578 P < 0.001; MAP, r = -0.627, P < 0.0001). Our results demonstrate that transduction is blunted in individuals with higher basal MSNA, suggesting that blunted neurocardiovascular transduction is a physiological adaptation to elevated MSNA rather than an effect or adaptation specific to chronic hypoxic exposure.NEW & NOTEWORTHY This study has identified that sympathetically mediated blood pressure regulation is reduced following ascent to high-altitude. Additionally, we show that high altitude Andean natives have reduced blood pressure responsiveness to sympathetic nervous activity (SNA) compared with Nepalese Sherpa. However, basal sympathetic activity is inversely related to the magnitude of SNA-mediated fluctuations in blood pressure regardless of population or condition. These data set a foundation to explore more precise mechanisms of blood pressure control under conditions of persistent sympathetic activation and hypoxia.

Knowledge translation and social media: Twitter data analysis of the 2019 Canadian Guideline for Physical Activity throughout Pregnancy.

OBJECTIVES: Despite extensive evidence demonstrating the benefits of prenatal physical activity (PA), inefficient knowledge translation may contribute to low rates of PA during pregnancy. This study aimed to examine the impact of the 2019 Canadian Guideline for Physical Activity throughout Pregnancy (hereafter Guideline) on knowledge transmission via Twitter. METHODS: Tweets containing keywords regarding prenatal PA were mined using the Twitter Application Programming Interface 1 month prior to (PRE), and 2 months following (POST-Month1 and Month2) Guideline release (October 18, 2018). The volume, user and location of Tweets relevant to prenatal PA were analyzed. RESULTS: In this 3-month period, 19,944 Tweets were collected. After randomization to select 10% of the sample, 1995 Tweets were analyzed. Tweets related to prenatal PA increased following Guideline release (PRE = 318/674 [45%]; POST-Month1 = 377/755 [50%]); however, this was not sustained into POST-Month2 (202/566 [36%]). The main users Tweeting about prenatal PA were categorized as 'General Population' (33%), whereas top users Tweeting about the Guideline were 'Academics' (25%), 'Exercise Specialists' (27%) and 'Medical Professionals' (20%). POST-Guideline, Tweets originated from users in 42 countries (PRE = 28). CONCLUSIONS: Twitter can be an effective tool for knowledge transmission of PA guidelines to a variety of end-users around the globe.

RéSUMé: OBJECTIFS: Malgré les nombreuses preuves démontrant les avantages de l'activité physique (AP) prénatale, l'application inefficace de ces connaissances pourrait contribuer aux faibles taux d'AP pendant la grossesse. Dans notre étude, nous avons examiné l'impact de l'édition 2019 des Directives canadiennes en matière d'activité physique pendant la grossesse (ci-après Directives) sur la transmission des connaissances via Twitter. MéTHODE: Les minimessages contenant des mots clés en lien avec l'AP prénatale ont été explorés à l'aide de l'interface de programmation de l'application Twitter un mois avant (PRÉ) et deux mois après (POST-Mois1 et POST-Mois2) la date de parution des Directives (le 18 octobre 2018). Le volume, les utilisateurs et utilisatrices et le lieu géographique des minimessages en lien avec l'AP prénatale ont été analysés. RéSULTATS: Au cours de cette période de trois mois, 19 944 minimessages ont été collectés. Après une sélection aléatoire de 10 % de l'échantillon, 1 995 mini messages ont été analysés. Les minimessages liés à l'AP prénatale ont augmenté après la parution des Directives (PRÉ = 318/674 [45 %]; POST-Mois1 = 377/755 [50 %]), mais cette augmentation ne s'est pas maintenue le deuxième mois suivant la parution (POST-Mois2 = 202/566 [36 %]). Les principaux utilisateurs et utilisatrices ayant publié des minimessages sur Twitter au sujet de l'AP prénatale étaient catégorisés comme faisant partie de la « population générale ¼ (33 %), mais les principaux utilisateurs et utilisatrices ayant publié des minimessages sur les Directives étaient des « universitaires ¼ (25 %), des « spécialistes de l'exercice ¼ (27 %) et des « professionnels de la santé ¼ (20 %). Après la parution des Directives (POST), les minimessages provenaient d'utilisateurs et d'utilisatrices situés dans 42 pays (PRÉ = 28). CONCLUSIONS: Twitter peut être un outil efficace de transmission des connaissances sur les directives en matière d'AP à un éventail d'utilisateurs et d'utilisatrices du monde entier.

Why can't I exercise during pregnancy? Time to revisit medical 'absolute' and 'relative' contraindications: systematic review of evidence of harm and a call to action.

BACKGROUND: Clinical guidelines recommend pregnant women without contraindication engage in regular physical activity. This is based on extensive evidence demonstrating the safety and benefits of prenatal exercise. However, certain medical conditions or contraindications warrant a reduction, modification or cessation of activity due to potential health risks. AIM: To review and evaluate the evidence related to medical disorders which may warrant contraindication to prenatal exercise. METHODS: Online databases were searched up to 5 April 2019. Forty-four unique studies that reported data on our Population (pregnant women with contraindication to exercise), Intervention (subjective/objective measures of acute or chronic exercise), Comparator (not essential) and Outcomes (adverse maternal or fetal outcomes) were included in the review. KEY FINDINGS: We found that the majority of medical conditions listed as contraindications were based on expert opinion; there is minimal empirical evidence to demonstrate harm of exercise and benefit of activity restriction. We identified 11 complications (eg, gestational hypertension, twin pregnancy) previously classified as contraindications where women may in fact benefit from regular prenatal physical activity with or without modifications. However, the evidence suggests that severe cardiorespiratory disease, placental abruption, vasa previa, uncontrolled type 1 diabetes, intrauterine growth restriction, active preterm labour, severe pre-eclampsia and cervical insufficiency are associated with strong potential for maternal/fetal harm and warrant classification as absolute contraindications. CONCLUSION: Based on empirical evidence, we provide a call to re-evaluate clinical guidelines related to medical disorders that have previously been considered contraindications to prenatal exercise. Removing barriers to physical activity during pregnancy for women with certain medical conditions may in fact be beneficial for maternal-fetal health outcomes.

The Menopause Alters Aerobic Adaptations to High-Intensity Interval Training.

INTRODUCTION: Postmenopausal women have lower resting cardiac function than premenopausal women, but whether the menopause influences maximal cardiac output and hence exercise capacity is unclear. It is possible that premenopausal and postmenopausal women achieve similar improvements in maximal aerobic capacity (V˙O2max) and cardiac output with exercise training via different regional left ventricular muscle function ("LV mechanics"), as suggested by in vitro and animal studies. The aim of this study was to investigate the effects of the menopause on LV mechanics and adaptations to exercise training. METHODS: Twenty-five healthy untrained middle-age women (age, 45-58 yr; 11 premenopausal, 14 postmenopausal) completed 12 wk of exercise training. Before and after exercise training, (i) V˙O2max and blood volume were determined, and (ii) LV mechanics were assessed using echocardiography at rest and during two submaximal physiological tests - lower-body negative pressure and supine cycling. RESULTS: The increase in V˙O2max after exercise training was 9% smaller in postmenopausal than premenopausal women, concomitant with a smaller increase in blood volume (P < 0.05). However, cardiac output and LV volumes were not different between premenopausal and postmenopausal women (P > 0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in premenopausal women during the physiological tests after exercise training (P < 0.05). CONCLUSIONS: These findings are the first to confirm altered LV mechanics in postmenopausal women. In addition, the reduced aerobic adaptability to exercise training in postmenopausal women does not appear to be a central cardiac limitation and may be due to altered blood volume distribution and lower peripheral adaptations.

Evidence for a physiological role of pulmonary arterial baroreceptors in sympathetic neural activation in healthy humans.

KEY POINTS: In an anaesthetised animal model, independent stimulation of baroreceptors in the pulmonary artery elicits reflex sympathoexcitation. In humans, pulmonary arterial pressure is positively related to basal muscle sympathetic nerve activity (MSNA) under conditions where elevated pulmonary pressure is evident (e.g. high altitude); however, a causal link is not established. Using a novel experimental approach, we demonstrate that reducing pulmonary arterial pressure lowers basal MSNA in healthy humans. This response is distinct from the negative feedback reflex mediated by aortic and carotid sinus baroreceptors when systemic arterial pressure is lowered. Afferent input from pulmonary arterial baroreceptors may contribute to sympathetic neural activation in healthy lowland natives exposed to high altitude. ABSTRACT: In animal models, distension of baroreceptors located in the pulmonary artery induces a reflex increase in sympathetic outflow; however, this has not been examined in humans. Therefore, we investigated whether reductions in pulmonary arterial pressure influenced sympathetic outflow and baroreflex control of muscle sympathetic nerve activity (MSNA). Healthy lowlanders (n = 13; 5 females) were studied 4-8 days following arrival at high altitude (4383 m; Cerro de Pasco, Peru), a setting that increases both pulmonary arterial pressure and sympathetic outflow. MSNA (microneurography) and blood pressure (BP; photoplethysmography) were measured continuously during ambient air breathing (Amb) and a 6 min inhalation of the vasodilator nitric oxide (iNO; 40 ppm in 21% O2 ), to selectively lower pulmonary arterial pressure. A modified Oxford test was performed under both conditions. Pulmonary artery systolic pressure (PASP) was determined using Doppler echocardiography. iNO reduced PASP (24 ± 3 vs. 32 ± 5 mmHg; P < 0.001) compared to Amb, with a similar reduction in MSNA total activity (1369 ± 576 to 994 ± 474 a.u min-1 ; P = 0.01). iNO also reduced the MSNA operating point (burst incidence; 39 ± 16 to 33 ± 17 bursts·100 Hb-1 ; P = 0.01) and diastolic operating pressure (82 ± 8 to 80 ± 8 mmHg; P < 0.001) compared to Amb, without changing heart rate (P = 0.6) or vascular-sympathetic baroreflex gain (P = 0.85). In conclusion, unloading of pulmonary arterial baroreceptors reduced basal sympathetic outflow to the skeletal muscle vasculature and reset vascular-sympathetic baroreflex control of MSNA downward and leftward in healthy humans at high altitude. These data suggest the existence of a lesser-known reflex input involved in sympathetic activation in humans.