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During pregnancy, assessment of cardiac output (𝑄̇), a fundamental measure of cardiovascular function, provides important insight into maternal adaptation. However, methods for dynamic 𝑄̇ measurement require validation. The purpose of this study was to estimate the agreement of 𝑄̇ 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 𝑄̇ 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 𝑄̇ determination in research involving young, healthy non-pregnant and pregnant women at rest or during dynamic challenge. Previously published 𝑄̇ data from studies utilising this method should be interpreted with caution.

In the general population, increased aortic stiffness is associated with an increased risk of cardiovascular events. Previous studies have demonstrated an increase in aortic stiffness in patients with a continuous flow left ventricular assist device (CF-LVAD). However, the association between aortic stiffness and common adverse events is unknown.Forty patients with a HeartMate II (HMII) (51 $ 11 years; 20% female; 25% ischemic) implanted between January 2011 and September 2017 were included. Two-dimensional transthoracic echocardiograms of the ascending aorta, obtained before HMII placement and early after heart transplant, were analyzed to calculate the aortic stiffness index (AO-SI). The study cohort was divided into patients who had an increased vs decreased AO-SI after LVAD support. A composite outcome of gastrointestinal bleeding, stroke, and pump thrombosis was defined as the primary end point and compared between the groups. While median AO-SI increased significantly after HMII support (AO-SI 4.4-6.5, P = .012), 16 patients had a lower AO-SI. Patients with increased (n = 24) AO-SI had a significantly higher rate of the composite end point (58% vs 12%, odds ratio 9.8, P.01). Similarly, those with increased AO-SI tended to be on LVAD support for a longer duration, had higher LVAD speed and reduced use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.Increased aortic stiffness in patients with a HMII is associated with a significantly higher rates of adverse events. Further studies are warranted to determine the causality between aortic stiffness and adverse events, as well as the effect of neurohormonal modulation on the conduit vasculature in patients with a CF-LVAD.

Left ventricular assist devices (LVADs) are associated with major vascular complications including stroke and gastrointestinal bleeding (GIB). These adverse vascular events may be the result of widespread vascular dysfunction resulting from pre-LVAD abnormalities or continuous flow during LVAD therapy. We hypothesized that pre-existing large artery atherosclerosis and/or abnormal blood flow as measured in carotid arteries using ultrasonography are associated with a post-implantation composite adverse outcome including stroke, GIB, or death. We retrospectively studied 141 adult HeartMate II patients who had carotid ultrasound duplex exams performed before and/or after LVAD surgery. Structural parameters examined included plaque burden and stenosis. Hemodynamic parameters included peak-systolic, end-diastolic, and mean velocity as well as pulsatility index. We examined the association of these measures with the composite outcome as well as individual subcomponents such as stroke. After adjusting for established risk factors, the composite adverse outcome was associated with pre-operative moderate-to-severe carotid plaque (OR 5.08, 95% CI 1.67-15.52) as well as pre-operative internal carotid artery stenosis (OR 9.02, 95% CI 1.06-76.56). In contrast, altered hemodynamics during LVAD support were not associated with the composite outcome. Our findings suggest that pre-existing atherosclerosis possibly in combination with LVAD hemodynamics may be an important contributor to adverse vascular events during mechanical support. This encourages greater awareness of carotid morphology pre-operatively and further study of the interaction between hemodynamics, pulsatility, and structural arterial disease during LVAD support.

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.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.The increase in V˙O2max after exercise training was 9% smaller in postmenopausal than premenopausal women, concomitant with a smaller increase in blood volume (P0.05). However, cardiac output and LV volumes were not different between premenopausal and postmenopausal women (P0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in premenopausal women during the physiological tests after exercise training (P0.05).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.

Cardiac output during exercise increases by as much as fivefold in the untrained man, and by as much as eightfold in the elite athlete. Increasing venous return is a critical but much overlooked component of the physiological response to exercise. Cardiac disorders such as constrictive pericarditis, restrictive cardiomyopathy and pulmonary hypertension are recognised to impair preload and cause exercise limitation; however, the effects of peripheral venous obstruction on cardiac function have not been well described. This manuscript will discuss how obstruction of the iliocaval venous outflow can lead to impairment in exercise tolerance, how such obstructions may be diagnosed, the potential implications of chronic obstructions on sympathetic nervous system activation, and relevance of venous compression syndromes in heart failure with preserved ejection fraction.

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. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

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.

Dehydration accrued during intense prolonged whole‐body exercise in the heat compromises peripheral blood flow and cardiac output (Q˙). A markedly reduced stroke volume (SV) is a key feature of the dehydration‐induced cardiovascular strain, but whether the lower output of the heart is mediated by peripheral or cardiac factors remains unknown. Therefore, we repeatedly quantified left ventricular (LV) volumes, LV mechanics (LV twist, a marker of systolic muscle function, and LV untwisting rate, an independent marker of LV muscle relaxation), left intra‐ventricular pressure gradients, blood volume and peripheral blood flow during 2 hr of cycling in the heat with and without dehydration (DEH: 4.0 ± 0.2% body mass loss and EUH: euhydration control, respectively) in eight participants (three females and five males). While brachial and carotid blood flow, blood volume, SV, LV end‐diastolic volume (LVEDV), cardiac filling time, systemic vascular conductance and Q˙ were reduced in DEH compared to EUH after 2 hr, LV twist and untwisting rate tended to be higher (p = .09 and .06, respectively) and intra‐ventricular pressure gradients were not different between the two conditions (p = .22). Furthermore, LVEDV in DEH correlated strongly with blood volume (r = .995, p, Dehydration reduces stroke volume and cardiac output during intense prolonged exercise in the heat, but the underlying peripheral and cardiac mechanisms are not fully understood. We show that the reduced stroke volume accounting for the impaired cardiac output is closely associated with diminished left ventricular filling secondary to decreased peripheral blood flow and volume, compromised venous return, and reduced cardiac filling time. These findings highlight the importance of peripheral mechanisms in cardiac performance during exercise.

Article published in The Journal of Physiology, available at https://doi.org/10.1113/JP276729

Cardiovascular function generally decreases with age, but whether this decrease differs between men and women is unclear. Our aims were twofold: (1) to investigate age-related sex differences in left ventricular (LV) structure, function and mechanics, and (2) to compare these measures between pre- and postmenopausal women in the middle-aged group.Resting echocardiography was performed in a cross-sectional sample of 82 healthy adults (14 young men, 19 middle-aged men, 15 young women, 34 middle-aged women: 15 premenopausal and 19 postmenopausal). Two-way ANOVAs were used to examine sex × age interactions, and t-tests to compare pre- and postmenopausal women (α 0.1).Normalized LV mass, stroke volume and end-diastolic volume were significantly lower in middle-aged than young men, but this difference was smaller between middle-aged and young women. Peak systolic apical mechanics were significantly greater in middle-aged men than in middle-aged women, but not between young men and women. Postmenopausal women had significantly lower LV relaxation and mechanics (torsion, twisting velocity and apical circumferential strain rates) compared with middle-aged premenopausal women.Our cross-sectional findings suggest that the hearts of men and women may age differently, with men displaying greater differences in LV volumes accompanied by differences in apical mechanics.

What is the topic of this review? This review discusses how implantation of continuous flow left ventricular assist devices impact arterial stiffness and outcome. What advances does it highlight? Not all patients implanted with continuous flow left ventricular assist devices show an increase in arterial stiffness. However, in those patients where arterial stiffness increases, levels of composite outcome (stroke, gastrointestinal bleeding, pump thrombosis and death) is significantly higher than those who's arterial stiffness does not increase.In parallel with the major advances in clinical care, technological advancements and implantation of mechanical circulatory support in patients with severe heart failure have resulted in these patients living longer. However, these patients are still at increased risk of stroke and gastrointestinal bleeding. The unique continuous flow produced by various left ventricular assist devices (LVADs) has been suggested as one potential reason for this increased risk of stroke and gastrointestinal bleeding. Furthermore, these continuous-flow (CF) devices challenge our understanding of circulatory blood pressure and flow regulation in relationship to organ health. In healthy pulsatile and dynamic systems, arterial stiffness is a major independent risk factor for stroke. However, to date, there are limited data regarding the impact of CF-LVAD therapy on arterial stiffness. The purpose of this report is to discuss the variable impact of CF-LVAD therapy on arterial stiffness and attempt to highlight some potential mechanisms linking these associations in this unique population.

Cardiac output (CO), along with blood pressure and vascular resistance, is one of the most important parameters of maternal hemodynamic function. Substantial changes in CO occur in normal pregnancy and in most obstetric complications. With the development of several non-invasive techniques for the measurement of CO, there is a growing interest in the determination of this parameter in pregnancy. These techniques were initially developed for use in critical-care settings and were subsequently adopted in obstetrics, often without appropriate validation for use in pregnancy. In this article, methods and devices for the measurement of CO are described and compared, and recommendations are formulated for their use in pregnancy, with the aim of standardizing the assessment of CO and peripheral vascular resistance in clinical practice and research studies on maternal hemodynamics. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Regular participation in exercise has long been known to result in cardiovascular adaptation. Historically, the ‘athlete’s heart’ hypothesis has encouraged a dichotomised view of the heart’s adaptation to sport, depending on whether the physical activity was either of isotonic activity (runners and swimmers) resulting in ‘cardiomegaly’ or of isometric effort (wrestlers and shot putters, ie, ‘strength’ athletes) with clear peripheral adaptations and an ‘obvious increase in cardiac size’.1 Today, the classification of sports according to their physiological demands acknowledges a greater diversity of exposure, depending on the physical activity, with an emphasis on a ‘graded transition’ between the main categories: dynamic, static and impact.2 Still, our understanding of the determinants of structural and functional cardiovascular adaptation to exercise are limited, and the consequences for health remain a matter of debate.3 In their Heart paper, Hedman et al 4 add to the current knowledge beyond the athlete’s heart by presenting data on blood pressure from a large cohort of young athletes. The authors aimed at investigating blood pressure in preparticipation screening, and to evaluate the role of blood pressure against left ventricular (LV) remodelling. Participants’ systolic and diastolic blood pressure was classified according to US and European hypertension guidelines. They observed that one-third of athletes presented with blood pressure exceeding systolic and/or diastolic thresholds of the current US guidelines. Furthermore, systolic blood pressure was associated with LV remodelling and altered diastolic cardiac function, but not systolic function. The findings contribute to our understanding of exercise-induced cardiovascular adaptation, and several …

Elevated blood pressure (BP) has been linked to adverse events during left ventricular assist device support. In this study we investigated the association between outpatient BP and stroke or suspected pump thrombosis among HeartMate II (HMII) recipients.We retrospectively studied 220 HMII patients. Serial outpatient BP measurements were averaged. Patients were categorized by: (1) mean arterial pressure (MAP), high (90 mm Hg) vs intermediate (80 mm Hg ≤ MAP ≤ 90 mm Hg) vs low (80 mm Hg); (2) systolic BP (SBP), high (≥101 mm Hg, median) vs low; and (3) pulse pressure (PP), high (≥22 mm Hg, median) vs low. To assess visit-to-visit BP variability, patients were divided in quartiles of standard deviation of MAP and SBP. The primary end-point was the composite of stroke or suspected pump thrombosis.The risk for the primary end-point was increased in the high MAP group (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.49 to 5.05, vs intermediate MAP; and 6.73, 1.9 to 23.9, vs low MAP). MAP had higher predictive value for the primary end-point compared with SBP (p = 0.05). Patients with high SBP had a higher rate of stroke (HR 2.8, 95% CI 1.09 to 7.17, vs low SBP). The combination of high SBP and low PP was associated with the highest risk for stroke. The lowest quartile of visit-to-visit MAP variability was associated with the highest risk for the primary end-point.Elevated outpatient BP is associated with increased risk for stroke or suspected pump thrombosis in HMII recipients. Reduced PP and low visit-to-visit BP variability may confer additional risk.

Purpose We previously showed that cerebrovascular reactivity (CVR) is reduced in heart failure (HF) patients and does not improve after left ventricular assist device (LVAD) HeartMate II (HMII) implantation, possibly because of low pulsatile physiology. Therefore, it is possible that the artificial pulse of the latest generation LVAD, the HeartMate3 (HM3), restores normal CVR. HM3 patients will have an increased CVR to a CO2-retention challenge compared with HF and HMII. Methods A total of 79 subjects (17 healthy, 30 HF, 15 HMII and 17 HM3) underwent angle-corrected transcranial Doppler sonography. Middle cerebral artery (MCA) velocity profiles were recorded before and at the end of a 30s breath hold. Mean flow velocity (MFV), peak flow velocity (Vmax), minimal flow velocity (Vmin), Pulsatility Index (PI) and Resistance Index (RI) were quantified. Statistical differences were determined using 2-way ANOVA (Breathhold x group). Results At baseline, HF patients with and without LVAD implantation had a decreased Vmax, MFV, PI and RI compared to healthy (all P Conclusion HM3 patients have a significantly improved CVR to a CO2-retention challenge compared with HMII patients. However, the acute CVR is not altered by the artificial pulse. Since CVR of HM3 patients remains reduced compared with healthy controls, further research is needed to understand the pathophysiology of cerebrovascular complications in LVAD.

Purpose Lack of nocturnal blood pressure (BP) reduction (BP dipping) has been associated with cerebrovascular and cardiovascular events in the general population. However, the effect of a deranged circadian BP variability between day and night has never been studied in patients on left ventricular assist device (LVAD) support, where stroke still represents a major complication. We hypothesized that decreased BP dipping significantly increases the risk of stroke in patients on LVAD support. Methods HeartMate II (HMII) outpatients were prospectively studied with an ambulatory BP monitor (Mobil-O-Graph) previously validated in this patient population. Systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were recorded every 30 minutes during the day and every hour during the night for 24 hours. Circadian patterns, expressed as the percentage of nocturnal SBP, DBP, and MAP reduction from daytime values, were assessed in Cox regression models with stroke as primary endpoint. Results 29 patients were studied (age 59 ±15 yrs, 76% male, 38% ischemic, 69% DT). 6 patients (20%) experienced a stroke 879±591 days post LVAD implant. Nocturnal reductions of SBP, DBP, and MAP were 5.0 ± 6.1%, 5.0 ± 5.6% and 5.0 ± 5.5%, respectively. Preserved nocturnal reductions of SBP (HR 0.790 [95% CI 0.658 - 0.949]), DBP (HR 0.707 [95% CI 0.559 - 0.894]) and MAP (HR 0.703 [95% CI 0.554 - 0.894]) were associated with a decreased risk of stroke. When patients were grouped by the median nocturnal reduction in MAP (5.4%), patients with reduced dipping had a significantly greater risk of stroke (Figure 1). Conclusion This study is the first to indicate that reduced BP dipping at night increases the risk of stroke in patients on HMII support. Further studies are warranted to investigate, mechanistically, the relationship between reduced BP dipping and sympathetic nervous system activation, and, clinically, its association with the risk of stroke in patients on HM3 support.

Purpose It is well established that continuous-flow left ventricular assist devices (LVAD) reduce pulsatility in the circulation. Consequently, the addition of an ‘artificial pulse’ to the HeartMate3 (HM3) LVAD has been expected to increase pulsatility. Yet, there has been no prospective study that has examined arterial hemodynamics of HM3 patients across the whole circulation, from large to muscular and microcirculatory arteries.Compared with HMII patients, HM3 patients will have a significantly increased arterial pulsatility across the whole circulation, and similar pulsatility to healthy individuals. Methods Pulsatility index (PI), peak systolic velocity (PSV), minimum velocity (Vmin) and mean flow velocity (MFV) of the common carotid, middle cerebral and central retinal arteries were quantified with angle-corrected 2D ultrasound in 141 volunteers (32 healthy controls, 42 heart failure (HF), 28 HM II, and 39 HM3 patients). To test the study hypothesis, data were statistically evaluated using 1-way ANOVA with Tukey's honestly significant difference test. Results Across all three artery locations, both PI and PSV of HM3 patients were significantly lower compared with healthy controls and HF (all P 0.05, Fig.1). Similarly, Vmin and MFV were not significantly different between HM3 and HMII (all P>0.05). Conclusion Despite the presence of an ‘artificial pulse’, pulsatility in patients implanted with the HM3 remains significantly lower than healthy controls and similar to HM II patients. Importantly, the lack of increased pulsatility in HM3 was explained by the flow pattern caused by the artificial pulse, which did not increase peak systolic velocity. These findings add insight into the remaining cardiovascular complications in HM3 patients and warrant further investigation.

Purpose While the impact of mean arterial pressure (MAP) on adverse events during left ventricular assist device (LVAD) support has been well established, there remains significant controversy regarding the impact of pulse pressure (PP) on clinical outcomes. We evaluated the impact of PP on post-implant hemocompatibility related adverse events (HRAE). Methods Using the INTERMACS registry, we identified patients who received a primary, durable continuous-flow LVAD with distinct systolic and diastolic blood pressure readings at 3-months post-implant. Patients requiring mechanical right ventricular assist devices or inotropic support were excluded. Patients were then stratified into low, medium, and high pulsatility tertiles. Kaplan-Meier survival estimates and Cox Proportional Hazard Models were used to assess the impact of pulsatility on HRAEs. Results A total of 4745 patients were classified into low (n=1508), medium (n=1675), and high (n=1562) pulsatility groups. There was no correlation between PP and MAP in this population (Figure 1A) and no clinically significant difference in MAP between the groups. Significant pre-implant determinants of pulsatility included female sex, BMI, race, device type, and peripheral vascular disease. Patients with lower pulsatility had more RV dysfunction and higher pro-BNP levels as compared to those with higher pulsatility. PP was a significant risk factor for stroke (HR: 1.09, CI: 1.04 - 1.15, p=0.001 per 10mmHg increase) independent of MAP. Patients with high MAP and high PP had the highest stroke risk (Figure 1B). PP was not associated with GI bleeding, device thrombosis. thromboembolic events, or post-implant survival. Conclusion High PP is associated with increased risk of stroke during LVAD support. Pulsatility may represent an additional therapeutic target in this patient population.

Background\ud Cardiac rehabilitation (CR) exercise training is beneficial after myocardial infarction (MI). Whilst the peripheral adaptations to training are well defined, little is known regarding the effect on left ventricular (LV) remodelling, particularly LV function. Efficient LV ejection and filling is achieved through deformation and rotation of the myocardium in systole and diastole – LV mechanics. The response of LV mechanics to CR exercise training in MI patients is unknown.\ud \ud Methods\ud In this observational exploratory study, 36 (of 40 enrolled) male, MI patients completed either 10-weeks of twice-weekly gym based cardiovascular exercise at 60–80% VO2peak (n = 18), or a non-exercise control period (n = 18). Cardiopulmonary exercise testing and speckle tracking echocardiography were performed at baseline and 10 weeks.\ud \ud Results\ud Compared to the non-exercise group, VO2peak improved with CR exercise training (Difference: +4.28 [95% CI: 1.34 to 7.23] ml.kg−1.min−1, P = 0.01). Neither conventional LV structural or functional indices, nor LV global longitudinal strain, significantly changed in either group. In contrast, LV twist and twist velocity decreased in the exercise group and increased in the non-exercise group (Difference: −3.95° [95% CI: −7.92 to 0.03°], P = 0.05 and −19.2°.s−1 [95% CI: −35.9 to −2.7°.s−1], P = 0.02, respectively).\ud \ud Conclusion\ud In MI patients who completed CR exercise training, LV twist and twist velocity decreased, whereas these parameters increased in patients who did not exercise. These preliminary data may indicate reverse LV functional remodelling and improved functional reserve. The assessment of LV twist may serve as an indicator of the therapeutic benefit of CR exercise training and should be investigated in larger trials.

The influence of cardiorespiratory fitness (CRF) on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, 2D strain imaging of the common carotid artery (CCA) provides novel information related to the intrinsic properties of the arterial wall. Therefore, this study aimed to assess the effect of CRF on both conventional indices of CCA stiffness and 2D strain parameters, at rest and following a bout of aerobic exercise in young healthy males. Short‐axis ultrasound images of the CCA were recorded in 34 healthy men [22 years (95%CI, 19–22)] before, and immediately after 5‐minutes of aerobic exercise (40% VO2max). Images were analysed for arterial diameter, peak circumferential strain (PCS), and peak systolic and diastolic strain rates (S‐SR, D‐SR). Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were simultaneously assessed and Petersons' elastic modulus (Ep) and Beta stiffness (β1) were calculated. Participants were separated post hoc into moderate and high fitness groups [VO2max: 48.9 ml.kg‐1 min‐1 (95%CI, 44.7–53.2) vs. 65.6 ml.kg‐1 min‐1 (95%CI, 63.1–68.1); P < 0.001]. Ep and β1 were similar between groups at baseline (P > 0.13) but were elevated in the moderate‐fitness group post‐exercise (P < 0.04). PCS and S‐SR were elevated in the high‐fitness group at both time‐points [3.0% (95%CI = 1.2, 4.9); P = 0.002; 0.401/s (95%CI = 0.085, 0.72); P = 0.02, respectively]. No group differences were observed in diameter, HR, SBP, DBP or D‐SR throughout the protocol (P > 0.05). High‐fit individuals exhibit elevated CCA PCS and S‐SR, which may reflect training‐induced adaptations that help to buffer the rise in pulse‐pressure and stroke volume during exercise.

Article published in Journal of Thoracic and Cardiovascular Surgery on 12 March 2018, available open access at: https://doi.org/10.1016/j.jtcvs.2017.10.160.

Clinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to 1) characterize the changes in Ca2+/calmodulin-dependent protein kinase type-IIδ (CaMKIIδ), growth signaling, structural proteins, fibrosis, apoptosis, and gene expression before and after LVAD support and 2) assess whether the duration of support correlated with improvement or worsening of reverse remodeling. Left ventricular apex tissue and serum pairs were collected in patients with dilated cardiomyopathy ( n = 25, 23 men and 2 women) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from healthy hearts ( n = 4) and normal serum from age-matched control hearts ( n = 4). The duration of LVAD support ranged from 48 to 1,170 days (median duration: 270 days). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Increased CaMKIIδ phosphorylation, nuclear myocyte enhancer factor 2, and cardiac MSTN significantly correlated with the duration of support. Phosphorylation of SMAD2 and apoptosis decreased with a shorter duration of LVAD support but increased with a longer duration of LVAD support. Further study is needed to define the optimal duration of LVAD support in patients with dilated cardiomyopathy. NEW & NOTEWORTHY A long duration of left ventricular assist device support may be detrimental for myocardial recovery, based on myocardial tissue experiments in patients with prolonged support showing significantly worsened activation of Ca2+/calmodulin-dependent protein kinase-IIδ, increased nuclear myocyte enhancer factor 2, increased myostatin and its signaling by SMAD2, and apoptosis as well as sustained histone deacetylase-4 phosphorylation, structural protein dysregulation, and fibrosis.

Purpose: In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. Methods: Twenty-four women with early stage breast cancer were randomly assigned to perform a 30-min, vigorous-intensity treadmill bout 24 h prior to each of four doxorubicin-containing chemotherapy treatments or to usual care. Established echocardiographic and circulating biomarkers of subclinical cardiotoxicity, as well as blood pressure and body weight were measured before the first and 7–14 days after the last treatment. The Rotterdam symptom checklist was used to assess patient-reported symptoms. Results: The exercise and usual care groups did not differ in the doxorubicin-related change in longitudinal strain, twist, or cardiac troponin. However, the four total exercise bouts prevented changes in hemodynamics (increased cardiac output, resting heart rate, decreased systemic vascular resistance, p < 0.01) and reduced body weight gain, prevalence of depressed mood, sore muscles, and low back pain after the last treatment (p < 0.05) relative to the usual care group. No adverse events occurred. Conclusions: An exercise bout performed 24 h prior to every doxorubicin treatment did not have an effect on markers of subclinical cardiotoxicity, but had a positive systemic effect on hemodynamics, musculoskeletal symptoms, mood, and body weight in women with breast cancer. A single exercise bout prior to chemotherapy treatments may be a simple clinical modality to reduce symptoms and weight gain among women with breast cancer.

Background: High pulsatility index (PI) in the cerebral circulation has been associated with increased prevalence of stroke (1). Interestingly, heart failure (HF) patients implanted with continuous-flow left ventricular assist devices (CF-LVADs) have increased rates of stroke despite presenting with dramatically lower pulse pressures compared with healthy individuals (20 mmHg vs. 30–40 mmHg). Characterising and understanding flow velocity profiles of the middle cerebral artery (MCA) may provide a useful and local marker of pulsatile energy transmitted into the brain of HF and CF-LVAD patients. Methods: PI and resistance index (RI) were quantified from Duplex ultrasound images (2D and pulsed-wave Doppler) of the MCA obtained in four heart failure patients (HF; 68 ± 7 yrs), eight CF-LVAD patients (59 ± 4 yrs) and 20 healthy controls (51 ± 7 yrs). Results: Compared with healthy controls, PI of the MCA was actually higher in the HF group (0.72 ± 0.16 vs. 1.32 ± 0.17, P < 0.0001), but markedly lower in patients on CF-LVAD (0.36 ± 0.21, P < 0.0001). However, RI was similar between healthy controls and HF patients (P > 0.05), and only lower in CF-LVAD patients (P < 0.0001). Conclusions: PI in the MCA is significantly higher in HF but markedly lower in CF-LVAD patients, relative to healthy controls. The higher PI in HF does not appear to be associated with an altered RI. Future work should examine the cerebrovascular outcomes associated with varying levels of pulsatility and resistance in both HF and CF-LVAD patients.

Limited data are available on hemodynamic responses to anesthetic protocols in wild-born chimpanzees (Pan troglodytes). Accordingly, this study characterized the heart rate (HR) and blood pressure responses to four anesthetic protocols in 176 clinically healthy, wild-born chimpanzees undergoing routine health assessments. Animals were anesthetized with medetomidine-ketamine (MK) (n = 101), tiletamine-zolazepam (TZ) (n = 30), tiletamine-zolazepam-medetomidine (TZM) (n = 24), or medetomidine-ketamine (maintained with isoflurane) (MKI) (n = 21). During each procedure, HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were regularly recorded. Data were grouped according to anesthetic protocol, and mean HR, SBP, and DBP were calculated. Differences between mean HR, SBP, and DBP for each anesthetic protocol were assessed using the Kruskall-Wallis test and a Dunn multiple comparisons post hoc analysis. To assess the hemodynamic time course response to each anesthetic protocol, group mean data (±95% confidence interval [CI]) were plotted against time postanesthetic induction. Mean HR (beats/min [CI]) was significantly higher in TZ (86 [80-92]) compared to MKI (69 [61-78]) and MK (62 [60-64]) and in TZM (73 [68-78]) compared to MK. The average SBP and DBP values (mm Hg [CI]) were significantly higher in MK (130 [126-134] and 94 [91-97]) compared to TZ (104 [96-112] and 58 [53-93]) and MKI (113 [103-123] and 78 [69-87]) and in TZM (128 [120-135] and 88 [83-93]) compared to TZ. Time course data were markedly different between protocols, with MKI showing the greatest decline over time. Both the anesthetic protocol adopted and the timing of measurement after injection influence hemodynamic recordings in wild-born chimpanzees and need to be considered when monitoring or assessing cardiovascular health.

An increasing number of end-stage heart failure patients are now implanted with continuous-flow left ventricular assist devices (CF-LVADs). Although this therapeutic approach is associated with improved clinical outcomes, continuous flow physiology reduces arterial pulse pressure and pulsatility to an extent that is unique to this population. Recent data suggest that high blood pressure (BP) contributes to life-threatening complications such as pump thrombosis and stroke of CF-LVAD patients. However, limited understanding of the distinct hemodynamics of these pumps makes measurement and, consequently, medical management of BP quite challenging. Here, we review the evolution of LVAD design, the impact of CF-LVAD flow, and "artificial pulse" technology on hemodynamics and BP measurement, as well as suggest new approaches for the assessment and interpretation of the unique physiology of modern LVADs.

Purpose Left ventricular assist device (LVAD) surgery is a life-prolonging therapy for advanced heart failure (HF). Despite many improvements over the years, LVADs continue to be associated with a high incidence of stroke and other vascular complications such as gastrointestinal bleeding (GIB). At present, the pathogenesis of these complications during LVAD support remains unclear. Abnormal structure and hemodynamics in large arteries are a potential contributor. We hypothesized that structural abnormalities and flow alterations will be significantly associated with stroke and a composite outcome of stroke, GIB, and death in HF patients before and during LVAD support. Methods We conducted a retrospective analysis of 141 carotid duplex studies in adult patients who received the HeartMate II LVAD. Clinical Doppler exams were evaluated before and after LVAD implantation. Parameters evaluated included peak-systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), pulsatility index (PI), ICA/CCA PSV ratio, plaque burden, and ICA stenosis. In addition, we noted demographics, outcomes, and LVAD speed parameters. Results Compared with HF patients, LVAD patients had decreased PSV (CCA: 80 vs. 50 cm/s, ICA: 72 vs. 56 cm/s; both P Conclusion We conclude that structural arterial disease in HF patients, namely carotid artery stenosis and plaque as evidenced by Doppler evaluation, was associated with stroke, GIB, and death during LVAD support while arterial flow parameters were not. Flow parameters during LVAD support were likewise unrelated to adverse events. Our findings support routine carotid duplex evaluation for clinical outcome prediction and encourage further study of the unique vascular physiology resulting from LVAD support.

Purpose In the normal, pulsatile circulation, the hemodynamic pattern of the middle cerebral artery (MCA) differs from the central retinal artery (CRA). Whether continuous flow from a left ventricular assist device (LVAD) alters this relationship is not known. Since serious adverse events in different end-organs, such as stroke and GI bleeding, are frequent in LVAD patients, comparing hemodynamics in different arterial beds may enhance our understanding of the specific pathophysiology of these complications. Hypothesis Because of continuous flow, hemodynamic patterns between the MCA and CRA are more similar in HeartMate II (HM II) patients compared with healthy individuals. Methods MCA and CRA time-averaged maximal flow velocity (TAMAX), pulsatility index (PI) and resistance index (RI) were determined using Doppler ultrasound with angle correction, in 20 HM II pts and 21 healthy individuals. To test the study hypothesis, data were statistically analysed for both group differences and group variances. Results Although PI and RI were markedly lower in HM II patients in both the MCA and CRA (P Conclusion The typical differences that are observed in small- and microcirculatory hemodynamics of healthy individuals are altered in HM II patients. Notably, the wide ranges of haemodynamics observed in the HM II group may carry important implications with respect to the pathophysiology of specific end-organ complications, and, eventually, the identification of high-risk patients.

Purpose In advanced heart failure (HF) patients, a normal cardiac output is restored after continuous-flow left ventricular assist device (CF-LVAD) implantation. Previous studies have suggested that cerebral autoregulation is preserved. However, it is not known whether CF-LVAD therapy affects the cerebrovascular reactivity to a metabolic challenge. Hypothesis CF-LVAD patients will have a similar cerebrovascular response to a CO2-retention challenge compared with HF patients and healthy controls. Methods Angle-corrected Doppler ultrasound images of the middle cerebral artery (MCA) were recorded immediately before and at the end of a 30s breathhold in 10 healthy controls, 4 HF and 7 CF-LVAD (HM II) patients. Time-averaged maximum blood velocity (TAMAX), peak flow velocity (Vmax), Pulsatility Index (PI) and Resistance Index (RI) were determined by tracing of the blood velocity envelope. Statistical differences were determined with 2-way ANOVA (% change is illustrated graphically). Results In the MCA, significant baseline differences in TAMAX, Vmax, PI and RI existed between groups (all P Conclusion A metabolic challenge has a differential impact on cerebrovascular hemodynamics of HF and CF-LVAD patients compared with healthy controls. The pilot data suggest that cerebrovascular reserve may be altered already in HF and not further modulated after CF-LVAD implantation.

Healthy pregnancy is characterised by progressive physiological adaptation of the maternal cardiovascular (CV) system that facilitates optimal fetal development. The adaptations that constitute a healthy or normal progression are not always evident, and, in particular, CV adaptation to pregnancy is highly individualised. Some women develop pregnancy-related CV dysfunction such as pre-eclampsia (PE). Typically, PE is diagnosed by the development of hypertension and proteinuria after 20 weeks of pregnancy and is the leading cause of maternal and perinatal mortality and morbidity. Despite continued efforts to improve the understanding of the aetiology, pathophysiology and subsequently treatment for the disease, CV changes in PE are not well understood. PE before 34 weeks (early onset PE) is believed to differ in pathogenesis from late onset PE (>34 weeks) and can be characterised by a haemodynamic profile of increased systemic vascular resistance (SVR) and lower cardiac output (CO). Early onset PE is more often associated with uteroplacental insufficiency and significant adverse maternal and perinatal outcomes. In contrast, late onset PE (>34 weeks) involves an increased CO and lower SVR and is less likely to be associated with uteroplacental insufficiency and adverse perinatal outcomes. It is not known if PE develops secondary to the CV maladaptation in pregnancy or if a preexisting CV dysfunction predisposes some women to develop PE. Screening, diagnosis and disease management would be vastly improved if more were known about the onset of the maladaptive process associated with PE. To date, a combination of maternal factors including medical history, body mass index, age, parity and blood pressure (BP) have been used to predict the development of PE. In the first trimester, arterial stiffness is significantly increased in women who develop PE. Current hypotheses speculate that CV dysfunction is evident very early in pregnancy in PE and precedes the clinical manifestation at a later stage but whether CV dysfunction is present before pregnancy remains to be elucidated.

Cardiac disease has been implicated as a leading cause of death in captive great apes. Trans-thoracic echocardiography provides clinically relevant information that may help differentiate between the myriad of different heart diseases and disorders, guide treatment and aid the management of great apes with underlying cardiac pathology. The purpose of this paper is to provide an outline of the procedures and methodologies required to conduct a thorough trans-thoracic echocardiogram of great apes under general anaesthesia. Basic logistical considerations are discussed before a detailed description of the procedures required for the assessment of overall cardiac structure and function. Using a thorough systematic approach, it is our belief that veterinary professionals may be better able to diagnose, treat and manage captive great apes with, or at risk of developing heart disease.

Individuals with high aerobic fitness have lower systolic left ventricular strain, rotation and twist (‘left ventricular (LV) mechanics’) at rest, suggesting a beneficial reduction in LV myofibre stress and more efficient systolic function. However, the mechanisms responsible for this functional adaptation are not known and the influence of aerobic fitness on LV mechanics during dynamic exercise has never been studied. We assessed LV mechanics, LV wall thickness and dimensions, central augmentation index (AIx), aortic pulse wave velocity (aPWV), blood pressure and heart rate in 28 males (age: 21±2 years SD) with a consistent physical activity level (no change>6 months). Individuals were examined at rest and during exercise (40% peak exercise capacity) and separated post hoc into a moderate and high aerobic fitness group (˙V(O2peak): 49 ± 5 and 63 ± 7ml kg−1 min−1, respectively, P 0.05).However, for the same AIx, the high ˙V(O2peak) group had significantly lower LV apical rotation (P =0.002) and LV twist (P =0.003) while basal rotation and strain indices did not differ between groups (P >0.05).We conclude that young males with high aerobic fitness have lower LVapical rotation at rest and during submaximal exercise that can occur without changes in gross LV structure, arterial haemodynamics or heart rate. The findings suggest a previously unknown type of physiological adaptation of the left ventricle that may have important implications for exercise training in older individuals and patient populations in which exercise training has previously failed to show clear benefits for LV function.

The purpose of this study was to determine whether the reduction in stroke volume (SV), previously shown to occur with dehydration and increases in internal body temperatures during prolonged exercise, is caused by a reduction in left ventricular (LV) function, as indicated by LV volumes, strain, and twist (“LV mechanics”). Eight healthy men [age: 20 ± 2, maximal oxygen uptake (VO2max): 58 ± 7 ml·kg−1·min−1] completed two, 1-h bouts of cycling in the heat (35°C, 50% peak power) without fluid replacement, resulting in 2% and 3.5% dehydration, respectively. Conventional and two-dimensional speckle-tracking echocardiography was used to determine LV volumes, strain, and twist at rest and during one-legged knee-extensor exercise at baseline, both levels of dehydration, and following rehydration. Progressive dehydration caused a significant reduction in end-diastolic volume (EDV) and SV at rest and during one-legged knee-extensor exercise (rest: Δ − 33 ± 14 and Δ − 21 ± 14 ml, respectively; exercise: Δ − 30 ± 10 and Δ − 22 ± 9 ml, respectively, during 3.5% dehydration). In contrast to the marked decline in EDV and SV, systolic and diastolic LV mechanics were either maintained or even enhanced with dehydration at rest and during knee-extensor exercise. We conclude that dehydration-induced reductions in SV at rest and during exercise are the result of reduced LV filling, as reflected by the decline in EDV. The concomitant maintenance of LV mechanics suggests that the decrease in LV filling, and consequently ejection, is likely caused by the reduction in blood volume and/or diminished filling time rather than impaired LV function.

Background— Contemporary understanding of exercise-induced cardiac remodeling is based on cross-sectional data and relatively short duration longitudinal studies. Temporal progression of exercise-induced cardiac remodeling remains incompletely understood. Methods and Results— A longitudinal repeated-measures study design using 2-dimensional and speckle-tracking echocardiography was used to examine acute augmentation phase (AAP; 90 days) and more extended chronic maintenance phase (39 months) left ventricular (LV) structural and functional adaptations to endurance exercise training among competitive male rowers (n=12; age 18.6±0.5 years). LV mass was within normal limits at baseline (93±9 g/m 2 ), increased after AAP (105±7 g/m 2 ; P =0.001), and further increased after chronic maintenance phase (113±10 g/m 2 ; P 2 ; P =0.004) with stable LV wall thickness (ΔLV wall thickness, 0.3±0.1 mm; P =0.63). In contrast, chronic maintenance phase LV hypertrophy was attributable to LV wall thickening (Δ LV wall thickness, 1.1±0.4 mm; P =0.004) with stable LV chamber volumes (ΔLV end-diastolic volume, 1±1 mL/m 2 ; P =0.48). Early diastolic peak tissue velocity increased during AAP (−11.7±1.9 versus −13.6±1.3 cm/s; P Conclusions— In a small sample of competitive endurance athletes, exercise-induced cardiac remodeling follows a phasic response with increases in LV chamber size, early diastolic function, and systolic twist in an acute augmentation phase of exercise training. This is followed by a chronic phase of adaptation characterized by increasing wall thickness and regression in LV twist. Training duration is a determinant of exercise-induced cardiac remodeling and has implications for the assessment of myocardial structure and function in athletes.

Objective Cardiac output, a fundamental parameter of cardiovascular function, has consistently been shown to increase across healthy pregnancy; however, the time course and magnitude of adaptation remains equivocal within published literature. The aim of the present meta-analyses was to comprehensively describe the pattern of change in cardiac output during healthy pregnancy. Method A series of meta-analyses of previously published cardiac output data during healthy, singleton pregnancies was completed. PubMed and Scopus databases were searched for studies published between 1996 and 2014. Included studies reported absolute values during a predetermined gestational age (non-pregnant, late first trimester, early and late second trimester, early and late third trimester, early and late postpartum). Cardiac output was measured through echocardiography, impedance cardiography or inert gas rebreathing. Observational data were meta-analysed at each gestational age using a random-effects model. If reported, related haemodynamic variables were evaluated. Results In total, 39 studies were eligible for inclusion, with pooled sample sizes ranging from 259 to 748. Cardiac output increased during pregnancy reaching its peak in the early third trimester, 1.5 L/min (31%) above non-pregnant values. The observed results from this study indicated a non-linear rise to this point. In the early postpartum, cardiac output had returned to non-pregnant values. Conclusion The present results suggest that cardiac output peaks in the early third trimester, following a non-linear pattern of adaptation; however, this must be confirmed using longitudinal studies. The findings provide new insight into the normal progression of cardiac output during pregnancy.

A long-standing question is whether pregnant females, who bear an increased biological stress, experience exacerbated cardiovascular responses during physiological challenge. At rest, pregnant females have reduced blood pressure, increased cardiac output, heart rate and stroke volume (1), with reported reductions in cardiac contraction and relaxation (2). Increased cardiac work may potentially exasperate impairments in function observed at rest. The aim of this study was to investigate the cardiovascular responses to an isolated increase in pressure in healthy nulliparous non-pregnant, primiparous pregnant (22–26 weeks gestation; n = 14) and primiparous postpartum (12–16 weeks after delivery; n = 13) females. The pressure challenge was elicited through a sustained isometric hold for approximately 5 minutes at 30% of maximum using an externally loaded handgrip dynamometer. Echocardiographic images were collected to measure cardiac volumes and mechanics. Blood pressure was monitored continuously using finger photoplethysmography. Analyses of covariance, with baseline measures as covariate, were completed to determine differences between groups (P =

Arterial wall mechanics likely play an integral role in arterial responses to acute physiological stress. Therefore, this study aimed to determine the impact of low and moderate intensity double‐leg press exercise on common carotid artery (CCA) wall mechanics using 2D vascular strain imaging. Short‐axis CCA ultrasound images were collected in 15 healthy men (age: 21 ± 3 years; stature: 176.5 ± 6.2 cm; body mass; 80.6 ± 15.3 kg) before, during, and immediately after short‐duration isometric double‐leg press exercise at 30% and 60% of participants' one‐repetition maximum (1RM: 317 ± 72 kg). Images were analyzed for peak circumferential strain (PCS), peak systolic and diastolic strain rate (S‐SR and D‐SR), and arterial diameter. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were simultaneously assessed and arterial stiffness indices were calculated post hoc. A two‐way repeated measures ANOVA revealed that during isometric contraction, PCS and S‐SR decreased significantly (P

Dehydration and hyperthermia reduces leg blood flow (LBF), cardiac output ( $$ \dot{Q} $$ ) and arterial pressure during whole-body exercise. It is unknown whether the reductions in blood flow are associated with dehydration-induced alterations in arterial blood oxygen content (C aO2) and O2-dependent signalling. This study investigated the impact of dehydration and concomitant alterations in C aO2 upon LBF and $$ \dot{Q} $$ . Haemodynamics, arterial and femoral venous blood parameters and plasma [ATP] were measured at rest and during one-legged knee-extensor exercise in 7 males in four conditions: (1) control, (2) mild dehydration, (3) moderate dehydration, and (4) rehydration. Relative to control, C aO2 and LBF increased with dehydration at rest and during exercise (C aO2: from 199 ± 1 to 208 ± 2, and 202 ± 2 to 210 ± 2 ml L−1 and LBF: from 0.38 ± 0.04 to 0.77 ± 0.09, and 1.64 ± 0.09 to 1.88 ± 0.1 L min−1, respectively). Similarly, $$ \dot{Q} $$ was unchanged or increased with dehydration at rest and during exercise, whereas arterial and leg perfusion pressures declined. Following rehydration, C aO2 declined (to 193 ± 2 mL L−1) but LBF remained elevated. Alterations in LBF were unrelated to C aO2 (r 2 = 0.13–0.27, P = 0.48–0.64) and plasma [ATP]. These findings suggest dehydration and concomitant alterations in C aO2 do not compromise LBF despite reductions in plasma [ATP]. While an additive or synergistic effect cannot be excluded, reductions in LBF during exercise with dehydration may not necessarily be associated with alterations in C aO2 and/or intravascular [ATP].

The healthy development of a fetus and the continued health of a newborn child are of primary interest to all beings. Unfortunately, pregnancy does not always progress favourably and can result in premature birth. Preterm infants are at high risk of complications in the neonatal period, such as chronic lung disease, and may develop cardiorespiratory problems in later life. As a consequence, different therapeutic strategies have been developed to improve the cardiorespiratory health of neonates. One popular choice is the use of glucocorticoid therapy, such as dexamethasone, because it reduces the relatively high prevalence of chronic lung disease in prematurely born offspring. However, negative side-effects of neonatal dexamethasone therapies are also known. For instance, the beneficial short-term effects of glucocorticoid therapy are accompanied by a variety of severe long-term cardiovascular complications, including pathological cardiac and vascular remodelling, hypertension, renal damage and insulin resistance (for specific references see Niu et al. 2013). These negative cardiovascular outcomes highlight the need for alternative therapies that achieve improved maturation of the respiratory system and alleviation of acute inflammatory symptoms associated with neonatal chronic lung disease, as well as maintained survival of the offspring into adulthood. To date, little is known about neonatal therapies that achieve these ambitious aims.

Heat stress increases limb blood flow and cardiac output (Q̇) in humans, presumably in sole response to an augmented thermoregulatory demand of the skin circulation. Here we tested the hypothesis that local hyperthermia also increases skeletal muscle blood flow at rest and during exercise. Hemodynamics, blood and tissue oxygenation, and muscle, skin, and core temperatures were measured at rest and during exercise in 11 males across four conditions of progressive whole body heat stress and at rest during isolated leg heat stress. During whole body heat stress, leg blood flow (LBF), Q̇, and leg (LVC) and systemic vascular conductance increased gradually with elevations in muscle temperature both at rest and during exercise ( r2 = 0.86–0.99; P < 0.05). Enhanced LBF and LVC were accompanied by reductions in leg arteriovenous oxygen (a-vO2) difference and increases in deep femoral venous O2 content and quadriceps tissue oxygenation, reflecting elevations in muscle and skin perfusion. The increase in LVC occurred despite an augmented plasma norepinephrine ( P < 0.05) and was associated with elevations in muscle temperature ( r2 = 0.85; P = 0.001) and arterial plasma ATP ( r2 = 0.87; P < 0.001). Isolated leg heat stress accounted for one-half of the increase in LBF with severe whole body heat stress. Our findings suggest that local hyperthermia also induces vasodilatation of the skeletal muscle microvasculature, thereby contributing to heat stress and exercise hyperemia. The increased limb muscle vasodilatation in these conditions of elevated muscle sympathetic vasoconstrictor activity is closely related to the rise in arterial plasma ATP and local tissue temperature.

In the originally published article systemic O2 delivery values reported in Fig. 3 are incorrect. The correct calculation for systemic O2 delivery (L min ) = arterial O2 content (mL L) * cardiac output (L min). The error in the manuscript was due to a miscalculation in the unit conversion from mL to L resulting in an erroneously high systemic O2 delivery across all conditions of dehydration/ rehydration and rest and exercise. Therefore, this error does not change the statistical results, the interpretation of the results nor the implication of the findings. The recalculations for each condition are as follows, control rest = 1.16 ± 0.06 L min, control exercise = 1.52 ± 0.07 L min, 2 % dehydration rest = 1.23 ± 0.03 L min, 2 % dehydration exercise = 1.58 ± 0.07 L min, 3.5 % dehydration rest = 1.37 ± 0.07 L min, 3.5 % dehydration exercise = 1.69 ± 0.06 L min, rehydration rest = 1.29 ± 0.04 L min, rehydration exercise = 1.58 ± 0.05 L min. Accordingly, the systemic O2 delivery panel from Fig. 3 has also changed.