Comparison between Modelflow® and echocardiography in the determination of cardiac output during and following pregnancy at rest and during exercise

During pregnancy, assessment of cardiac output (Q ̇), a fundamental measure of cardiovascular function, provides important insight into maternal adaptation. However, methods for dynamic Q ̇ measurement require validation. The purpose of this study was to estimate the agreement of Q ̇ measured by echocardiography and Modelflow® at rest and during submaximal exercise in non-pregnant (n = 18), pregnant (n = 15, 22-26 weeks gestation) and postpartum women (n = 12, 12-16 weeks post-delivery). Simultaneous measurements of Q ̇ derived from echocardiography [criterion] and Modelflow® were obtained at rest and during low-moderate intensity (25% and 50% peak power output) cycling exercise and compared using Bland-Altman analysis and limits of agreement. Agreement between echocardiography and Modelflow® was poor in non-pregnant, pregnant and postpartum women at rest (mean difference ± SD: -1.1 ± 3.4; -1.2 ± 2.9; -1.9 ± 3.2 L.min-1), and this remained evident during exercise. The Modelflow® method is not recommended for Q ̇ determination in research involving young, healthy non-pregnant and pregnant women at rest or during dynamic challenge. Previously published Q ̇ data from studies utilising this method should be interpreted with caution

Left ventricular mechanics in late second trimester of healthy pregnancy

Objective: To evaluate left ventricular (LV) mechanics in the second trimester of healthy pregnancy and to determine the influence of underpinning hemodynamics (heart rate (HR), preload and afterload) on LV mechanics during gestation. Methods: This was a cross‐sectional study of 18 non‐pregnant, 14 nulliparous pregnant (22–26 weeks' gestation) and 13 primiparous postpartum (12–16 weeks after delivery) women. All pregnant and postpartum women had uncomplicated, singleton gestations. Cardiac structure and function were assessed using echocardiography. LV mechanics, specifically longitudinal strain, circumferential strain and twist/untwist, were measured using speckle‐tracking echocardiography. Differences between groups were identified using ANCOVA, with age, HR, end‐diastolic volume (EDV) and systolic blood pressure (SBP) as covariates. Relationships between LV mechanics and hemodynamics were examined using Pearson's correlation. Results: There were no significant differences in LV structure and traditional measurements of systolic and diastolic function between the three groups. Pregnant women, compared with non‐pregnant ones, had significantly higher resting longitudinal strain (–22 ± 2% vs –17 ± 3%; P = 0.002) and basal circumferential strain (–23 ± 4% vs –16 ± 2%; P = 0.001). Apical circumferential strain and LV twist and untwist mechanics were similar between the three groups. No statistically significant relationships were observed between LV mechanics and HR, EDV or SBP within the groups. Conclusions: Compared to the non‐pregnant state, pregnant women in the second trimester of a healthy pregnancy have significantly greater resting systolic function, as assessed by LV longitudinal and circumferential strain. Contrary to previous work, these data show that healthy pregnant women should not exhibit reductions in resting systolic function between 22 and 26 weeks' gestation. The enhanced myocardial contractile function during gestation does not appear to be related to hemodynamic load and could be the result of other physiological adaptations to pregnancy

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

The menopause alters aerobic adaptations to high-intensity interval training

Introduction: Post-menopausal women have lower resting cardiac function than pre- menopausal women, but whether the menopause influences maximal cardiac output and hence exercise capacity is unclear. It is possible that pre- and post-menopausal women ̇ achieve similar improvements in peak aerobic capacity (V O2peak) 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-aged women (age 45–58 years; 11 pre-menopausal, 14 post-menopausal) completed 12 weeks of exercise training. Before and after exercise ̇ assessed using echocardiography at rest and during two submaximal physiological tests — lower body negative pressure (LBNP) and supine cycling. Results: The increase ̇ training, (i) V O2peak and blood volume were determined, and (ii) LV mechanics were in relative V O2peak after exercise training was 9% smaller in post-menopausal than pre- menopausal women, concomitant with a smaller increase in blood volume (P 0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in pre-menopausal women during the physiological tests after exercise training (P < 0.05). Conclusion: These findings are the first to confirm altered LV mechanics in post-menopausal women. In addition, the reduced aerobic adaptability to exercise training in post-menopausal women does not appear to be a central cardiac limitation, and may be due to altered blood volume distribution and lower peripheral adaptations

Global REACH: Assessment of brady-arrhythmias in Andeans and Lowlanders during apnea at 4330m

BACKGROUND: Ascent to altitude increases the prevalence of arrhythmogenesis in low-altitude dwelling populations (Lowlanders). High altitude populations (ie. Nepalese Sherpa) may have arrhythmias resistant adaptations that prevent arrhythmogenesis at altitude, though this has not been documented in other High altitude groups, including those diagnosed with chronic mountain sickness (CMS). We investigated whether healthy (CMS-) and CMS afflicted (CMS+) Andeans exhibit cardiac arrhythmias under acute apneic stress at altitude. METHODS AND RESULTS: Electrocardiograms (lead II) were collected in CMS- (N=9), CMS+ (N=8), and Lowlanders (N= 13) following several days at 4330m (Cerro de Pasco, Peru). ECG rhythm and HR were assessed at both rest and during maximal volitional apnea (End-Expiratory [EXP]). Both CMS- and CMS+ had similar basal HR (69 ± 8 beats/min vs. 62 ± 11 beats/min), while basal HR was higher in Lowlanders (77 ± 18 beats/min; P<0.05 versus CMS+). Apnea elicited significant bradycardia (nadir -32 ± 15 beats/min; P<0.01) and the development of arrhythmias in 8/13 Lowlanders (junctional rhythm, 3° atrio-venticular block, sinus pause). HR was preserved was prior to volitional breakpoint in both CMS- (nadir -6 ± 1 beat/min) and CMS+ (1 ±12 beats/min), with 2/17 Andeans developing arrhythmias ( 1 CMS+ and 1 CMS-; both Premature Atrial Contraction) prior to breakpoint. CONCLUSIONS: Andeans showed an absence of arrhythmias and preserved HR response to volitional apnea at altitude, demonstrating that potential cardio-resistant adaptations to arrhythmogenesis exist across permanent HA populations. Acclimatized Lowlanders have further demonstrated an increased prevalence of arrhythmias at altitude

Effects of prenatal exercise on fetal heart rate, umbilical and uterine blood flow: a systematic review and meta-analysis

Objective To perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics. Design Systematic review with random-effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcomes (FHR, beats per minute (bpm); uterine and umbilical blood flow metrics (systolic:diastolic (S/D) ratio; Pulsatility Index (PI); Resistance Index (RI); blood flow, mL/min; and blood velocity, cm/s)). Results ‘Very low’ to ‘moderate’ quality evidence from 91 unique studies (n=4641 women) were included. Overall, FHR increased during (mean difference (MD)=6.35bpm; 95% CI 2.30 to 10.41, I2=95%, p=0.002) and following acute exercise (MD=4.05; 95% CI 2.98 to 5.12, I2=83%, p\u3c0.00001). The incidence of fetal bradycardia was low at rest and unchanged with acute exercise. There were no significant changes in umbilical or uterine S/D, PI, RI, blood flow or blood velocity during or following acute exercise sessions. Chronic exercise decreased resting FHR and the umbilical artery S/D, PI and RI at rest. Conclusion Acute and chronic prenatal exercise do not adversely impact FHR or uteroplacental blood flow metrics

Global REACH 2018: Renal oxygen delivery is maintained during early acclimatization to 4330 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-hours of high-altitude exposure (high-altitude day1) but restored to sea-level values after one-week (high altitude day7); and 2) RDO2 would be associated with renal reactivity (RR), an index of acid base compensation at high-altitude. Twenty-four healthy lowlander participants were tested at sea-level (344m; Kelowna, Canada), on day1 and day7 at high-altitude (4330m; Cerro de Pasco, Peru). Cardiac output, renal blood flow, arterial and venous blood sampling for renin angiotensin-aldosterone-system hormones and NT pro-B type natriuretic peptides were collected at each time point. RR was calculated as: (Δ arterial bicarbonate)/(Δ partial pressure of arterial carbon dioxide) between sea-level and high-altitude day1, and sea-level and high-altitude day7. The main findings were: 1) RDO2 was initially decreased at high-altitude compared to sea-level (ΔRDO2: -22±17%, P<0.001), but was restored to sea-level values on high-altitude day7 (ΔRDO2: -6±14%, P=0.36). The observed improvements in RDO2 resulted from both changes in renal blood flow (Δ from high-altitude day1: +12±11%; P=0.008), and arterial oxygen content (Δ from high-altitude day1 +44.8±17.7%; P=0.006); and 2) RR was positively correlated with RDO2 on high-altitude day7 (r=0.70; P<0.001), but not high-altitude day1 (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

Highs and Lows of Sympathetic Neuro-cardiovascular Transduction: Influence of Altitude Acclimatization and Adaptation

High-altitude (>2500m) exposure results in increased muscle sympathetic nervous activity (MSNA) in acclimatizing lowlanders. However, little is known about how altitude affects MSNA in 66 indigenous high-altitude populations. Additionally, the relationship between MSNA and blood 67 pressure regulation (i.e., neurovascular transduction) at high-altitude is unclear. We sought to 68 determine 1) how high-altitude effects neuro-cardiovascular transduction and 2) whether 69 differences exist in neuro-cardiovascular transduction between low and high-altitude 70 populations. Measurements of MSNA (microneurography), mean arterial blood pressure (MAP; 71 finger photoplethysmography), and heart rate (electrocardiogram) were collected in: I) 72 lowlanders (n=14) at low (344m) and high-altitude (5050m), II) Sherpa highlanders (n=8; 73 5050m), and III) Andean (with and without excessive erythrocytosis) highlanders (n=15; 74 4300m). Cardiovascular responses to MSNA burst sequences (i.e. singlet, couplet, triplet, and 75 quadruplets) were quantified using custom software (coded in MATLAB, v2015b). Slopes were 76 generated for each individual based on peak responses and normalized total MSNA. High 77 altitude reduced neuro-cardiovascular transduction in lowlanders (MAP slope: high-altitude, 78 0.0075±0.0060 vs low-altitude, 0.0134±0.080; p=0.03). Transduction was elevated in Sherpa 79 (MAP slope, 0.012±0.007) compared to Andeans (0.003±0.002; p=0.001). MAP transduction 80 was not statistically different between acclimatizing lowlanders and Sherpa (MAP slope, p=0.08) 81 or Andeans (MAP slope, p=0.07). When accounting for resting MSNA (ANCOVA), transduction 82 was inversely related to basal MSNA (bursts/min) independent of population (RRI, r= 0.578 83 p<0.001; MAP, r= -0.627 p<0.0001). Our results demonstrate transduction is blunted in 84 individuals with higher basal MSNA, suggesting blunted neuro-cardiovascular transduction is a 85 physiological adaptation to elevated MSNA rather than an effect or adaptation specific to 86 chronic hypoxic exposure

Global REACH 2018: Andean Highlanders, Chronic Mountain Sickness and the Integrative Regulation of Resting Blood Pressure

High‐altitude maladaptation syndrome chronic mountain sickness (CMS) is characterised by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in 8 Andean natives with CMS ([Hb] 22.6 ± 0.9 g/dL) and 7 healthy highlanders ([Hb] 19.3 ± 0.8 g/dL) at their resident altitude (Cerro de Pasco, Peru; 4383 m). 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 ± 0.7cP; 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 ± 50msec; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs 8.8 ± 2.6msec·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 ± 13bursts·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

The 2018 Global Research Expedition on Altitude-related Chronic Health (REACH) to Cerro de Pasco, Peru: An Experimental Overview

In 2016, the international research team - Global Research Expedition onAltitude-related Chronic Health (REACH) - was established and executed a high altituderesearch expedition to Nepal. The team consists of ~45 students, principal investigatorsand physicians with the common objective of conducting experiments focused on highaltitude adaptation in lowlanders, and highlanders with lifelong exposure to high altitude.In 2018, Global REACH traveled to Peru where we performed a series of experiments inthe Andean highlanders. The experimental objectives, organization and characteristics,and key cohort data from Global REACH's latest research expedition are outlined herein.Herein, fifteen major studies are described that aimed to elucidate the physiologicaldifferences in high altitude acclimatization between lowlanders (n=30) and Andean bornhighlanders with (n=22) and without (n=45) Excessive Erythrocytosis (EE). Afterbaseline testing in Kelowna, BC, Canada (344m), Global REACH travelled to Lima, Peru(~80 m), and then ascended by automobile to Cerro de Pasco, Peru (~4300m) whereexperiments were conducted over 25 days. The core studies focused on elucidating themechanism(s) governing cerebral and peripheral vascular function, cardiopulmonaryregulation, exercise performance, and autonomic control. Despite encountering seriouslogistical challenges, each of the proposed studies were completed at both sea level andhigh altitude amounting to ~780 study sessions and >3000 hrs of experimental testing.Participant demographics and data related to acid-base balance and exercise capacityare presented. The collective findings will contribute to our understanding of howlowlanders and Andean highlanders have adapted under high altitude stress