Maria T. E. Hopman

Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk.

Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans

Flow‐mediated dilatation (FMD) of the brachial and radial arteries is an important research tool for assessment of endothelial function in vivo, and is nitric oxide (NO) dependent. The leg skeletal muscle vascular bed is an important territory for studies in exercise physiology. However, the role of endothelial NO in the FMD response of lower limb arteries has never been investigated. The purpose of this study was to examine the contribution of NO to FMD in the superficial femoral artery in healthy subjects. Since physical inactivity may affect endothelial function, and therefore NO availability, spinal cord‐injured (SCI) individuals were included as a model of extreme deconditioning. In eight healthy men (34 ± 13 years) and six SCI individuals (37 ± 10 years), the 5 min FMD response in the superficial femoral artery was assessed by echo‐Doppler, both during infusion of saline and during infusion of the NO synthase blocker NG‐monomethyl‐l‐arginine (l‐NMMA). In a subset of the controls (n= 6), the 10 min FMD response was also examined using the same procedure. The 5 min FMD response in controls (4.2 ± 0.3%) was significantly diminished during l‐NMMA infusion (1.0 ± 0.2%, P < 0.001). In SCI, l‐NMMA also significantly decreased the FMD response (from 8.2 ± 0.4% during saline to 2.4 ± 0.5% during l‐NMMA infusion). The hyperaemic flow response during the first 45 s after cuff deflation was lower in both groups during infusion of l‐NMMA, but the effect of l‐NMMA on FMD persisted in both groups after correction for the shear stress stimulus. The 10 min FMD was not affected by l‐NMMA (saline: 5.4 ± 1.6%, l‐NMMA: 5.6 ± 1.5%). Superficial femoral artery FMD in response to distal arterial occlusion for a period of 5 min is predominantly mediated by NO in healthy men and in the extremely deconditioned legs of SCI individuals.

Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training

The number of hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is thought to be a marker for neovascularization and vascular repair. Because physical inactivity and aging are risk factors for cardiovascular diseases, these factors may influence the numbers of HSCs and EPCs. Therefore, we examined baseline and exercise‐induced levels of HSCs and EPCs in sedentary and trained young and older men. To study the role of aging in eight sedentary young (19–28 years) and eight sedentary older men (67–76 years), baseline and acute exercise‐induced numbers of HSCs (CD34+‐cells) and EPCs (CD34+/VEGFR‐2+‐cells) were quantified by fluorescence‐activated cell sorter (FACS) analysis. To examine the effect of chronic training, eight age‐matched trained young men (18–28 years) were compared with sedentary young men, whereas older men performed an 8‐week endurance training. Older men showed significantly lower baseline and exercise‐induced levels of HSCs/EPCs than the young men (P < 0.05). In young and older men, acute exercise significantly increased HSCs (P < 0.01), but not EPCs. The absolute increase in numbers of HSCs was attenuated in older men (P = 0.03). Apart from the lower baseline numbers of EPCs after chronic training in older men, training status did not alter baseline or exercise‐induced levels of HSCs/EPCs in young and older men. We concluded that advancing age results in lower circulating numbers of HSCs and EPCs and attenuates the acute exercise‐induced increase in HSCs. Interestingly, in young as well as in older men chronic endurance training does not affect baseline and exercise‐induced numbers of HSCs and EPCs.

Brachial Artery Blood Flow Responses to Different Modalities of Lower Limb Exercise

INTRODUCTION/PURPOSE Cycling is associated with a reproducible systolic anterograde and diastolic retrograde flow pattern in the brachial artery (BA) of the inactive upper limb, which results in endothelial nitric oxide (NO) release. The purpose of this study was to examine the impact of different types and intensities of lower limb exercise on the BA flow pattern. METHODS We examined BA blood flow and shear rate patterns during cycling, leg kicking, and walking exercise in 12 young subjects (24 +/- 3 yr). BA diameter, blood flow, and shear rate were assessed at baseline (1 min) and at three incremental intensity levels of cycling (60, 80, and 120 W), bilateral leg kicking (5, 7.5, and 10 kg), and walking (3, 4, and 5 km x h(-1)), performed for 3 min each. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter and anterograde/retrograde blood flow and shear rate continuously across the cardiac cycle. RESULTS BA mean blood flow and shear rate increased significantly throughout each exercise protocol (P < 0.001), and BA anterograde blood flow and shear rate showed comparable increases throughout each protocol (P < 0.001). Retrograde blood flow and shear rate, however, demonstrated a significant increase during cycling and walking (P < 0.001) but not during leg kicking. CONCLUSION Rhythmic lower limb exercise (cycling and walking) results in an increase in BA systolic anterograde blood flow and shear rate, directly followed by a large retrograde flow and shear rate. This typical pattern, previously linked with endothelial NO release, is not present during a different type of exercise such as leg kicking.

Heterogeneity in conduit artery function in humans: impact of arterial size.

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.

Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans

Flow-mediated dilatation (FMD) has become a commonly applied approach for the assessment of vascular function and health in humans. Recent studies emphasize the importance of normalizing the magnitude of FMD to its apparent eliciting stimulus, the postdeflation arterial shear. However, the relationship between shear stress and the magnitude of FMD may differ between groups. The aim of this study was to examine the relationship between the brachial FMD and four different indexes of postdeflation shear rate (SR) in healthy children (n = 51, 10 +/- 1 yr) and young (n = 57, 27 +/- 6 yr) and older (n = 27, 58 +/- 4 yr) adults. SR was calculated from deflation (time 0) until 9 s (peak), 30 s (0-30), 60 s (0-60), or until the time-to-peak diameter in each individual (0-ttp). Edge detection and wall tracking of high resolution B-mode arterial ultrasound images were used to calculate the conduit artery diameter. In young adults, the brachial artery FMD demonstrated a significant correlation with the area under the SR curve (SR(AUC)) 0-30 s (r(2) = 0.12, P = 0.009), 0-60 s (r(2) = 0.14, P = 0.005), and 0-ttp (r(2) = 0.14, P = 0.005) but not for the peak SR(AUC) 0-9 s (r(2) = 0.04, P = 0.12). In children and older adults, the magnitude of the brachial artery FMD did not correlate with any of the four SR(AUC) stimuli. These findings suggest that in young subjects, postdeflation SR(AUC) correlates moderately with the magnitude of the FMD response. However, the relationship between FMD and postdeflation shear appears to be age dependent, with less evidence for an association in younger and older subjects. Therefore, we support presenting SR(AUC) stimuli but not normalizing FMD responses for the SR(AUC) when using this technique.

Systematic review of the effects of physical exercise training programmes in children and young adults with congenital heart disease

BACKGROUND Most patients with congenital heart disease (ConHD) do not perform regular physical exercise. Consensus reports have stated that exercise should be encouraged and regularly performed in these patients, but this is not common practise. We reviewed the literature on actual evidence for either negative or positive effects of physical exercise training programmes in children and young adults with ConHD. METHODS Using the Medline database, we systematically searched for articles on physical exercise training programmes in ConHD. RESULTS A total of 31 articles met all inclusion criteria; in total, 621 subjects (age range 4 to 45 years) were included. Most studies used training programmes with a duration of 12 weeks. On average, the number of training sessions was 3 times per week. In 12 studies, training intensity was set at a percentage of peak heart rate. Outcome measures reported were PeakVO2, activity levels and muscle strength. Twenty-three studies (72%) found a significant positive change in the main outcome measure after the physical exercise training period. None of the studies reported negative findings related to physical exercise training in ConHD. Cardiac effects have hardly been studied. CONCLUSION In most studies, participation in a physical exercise training programme was safe and improved fitness in children and young adults with ConHD. We recommend that patients with ConHD participate in physical exercise training. Cardiac effects need to be studied more extensively.

Walking Ability and Quality of Life in Subjects With Transfemoral Amputation: A Comparison of Osseointegration With Socket Prostheses

OBJECTIVE To investigate walking ability and quality of life of osseointegrated leg prostheses compared with socket prostheses. DESIGN Prospective case-control study. SETTING University medical center. PARTICIPANTS Subjects (N=22) with transfemoral amputation (1 bilateral) referred to our center because of socket-related skin and residual limb problems resulting in limited prosthesis use. Their mean age was 46.5 years (range, 23-67y) and mean time since amputation was 16.4 years (range, 2-45y). Causes of amputation were trauma (n=20) and tumor (n=2). INTERVENTION Implantation of an osseointegration prosthesis (OIP). MAIN OUTCOME MEASURES Global score of the Questionnaire for Persons With a Transfemoral Amputation (Q-TFA), prosthesis use, 6-minute walk test (6MWT), Timed Up & Go (TUG) test, and oxygen consumption during treadmill walking. RESULTS With the socket prosthesis, the mean ± SD Q-TFA global score, prosthesis use, 6MWT, TUG, and oxygen consumption were 39±4.7 points, 56±7.9h/wk, 321±28m, 15.1±2.1 seconds, and 1330±310mL/min, respectively, and significantly improved with OIP to 63±5.3 points, 101±2.4h/wk, 423±21m, 8.1±0.7 seconds, and 1093±361mL/min, respectively. CONCLUSIONS Osseointegration is a suitable intervention for persons whose prosthesis use is reduced because of socket-related problems. Subjects with OIP significantly increased their walking ability and prosthesis-related quality of life.

Vascular adaptations to 8-week cycling training in older men

Aim:  Because age‐related changes in the large conduit arteries (increased wall thickness, and attenuated arterial compliance and endothelial function) are associated with cardiovascular pathology, prevention is of paramount importance. The effects of endurance training (i.e. walking or cycling) in older humans are assessed in cross‐sectional studies, examining the brachial and carotid arteries (supplying non‐trained areas). The purpose of this study was to assess the effects of 8‐week endurance training in older men on conduit artery characteristics in the trained and non‐trained vascular beds.

Reproducibility of blood flow and post- occlusive reactive hyperaemia as measured by venous occlusion plethysmography

Venous occlusion plethysmography is commonly used as a tool to assess BF (blood flow) and VR (vascular resistance) at baseline and during PORH (post-occlusive reactive hyperaemia). However, little is known about the reproducibility of this method. The purpose of the present study was to investigate short- (hours) and medium (week)-term reproducibility of forearm, calf and thigh BF and VR at baseline and during PORH. Reproducibility was assessed by the CV (coefficient of variation). In eight subjects, baseline BF and VR of the forearm, calf and thigh were measured using venous occlusion plethysmography (50 mmHg). PORH and minimal VR were measured after 13 min of arterial occlusion (220 mmHg). Reproducibility of baseline forearm and calf BF was acceptable and in agreement with previous studies (CV, 12.9-21.2%). Short- and medium-term reproducibility of thigh BF was good (CV, 5.9% and 8.7% respectively). Baseline VR showed acceptable-to-good reproducibility for forearm, calf and thigh (8.3-22.5%). Forearm PORH showed a CV of 6.1% (short term) and 8.6% (medium term); this was 6.1% (short term) and 6.4% (medium term) for the calf and 6.4% (short term) and 8.0% (medium term) for the thigh. Minimal VR showed good-to-acceptable reproducibility (CV, 6.1-11.7%). In conclusion, forearm, calf and thigh BF and PORH measured by plethysmography have an acceptable-to-good short- and medium-term reproducibility. Short- and medium-term reproducibility of forearm and calf baseline BF are acceptable and thigh baseline BF has a good short- and medium-term reproducibility. Therefore plethysmography is a suitable low-cost tool to assess thigh baseline BF and PORH.