Angela L. Spence

Exercise and vascular adaptation in asymptomatic humans

Beneficial effects of exercise training on the vasculature have been consistently reported in subjects with cardiovascular risk factors or disease, whereas studies in apparently healthy subjects have been less uniform. In this review, we examine evidence pertaining to the impact of exercise training on conduit and resistance vessel function and structure in asymptomatic subjects. Studies of arterial function in vivo have mainly focused on the endothelial nitric oxide dilator system, which has generally been shown to improve following training. Some evidence suggests that the magnitude of benefit depends upon the intensity or volume of training and the relative impact of exercise on upregulation of dilator pathways versus effects of inflammation and/or oxidation. Favourable effects of training on autonomic balance, baroreflex function and brainstem modulation of sympathetic control have been reported, but there is also evidence that basal vasoconstrictor tone increases as a result of training such that improvements in intrinsic vasodilator function and arterial remodelling are counterbalanced at rest. Studies of compliance suggest increases in both the arterial and the venous sides of the circulation, particularly in older subjects. In terms of mechanisms, shear stress appears to be a key signal to improvement in vascular function, whilst increases in pulse pressure and associated haemodynamics during bouts of exercise may transduce vascular adaptation, even in vascular beds which are distant from the active muscle. Different exercise modalities are associated with idiosyncratic patterns of blood flow and shear stress, and this may have some impact on the magnitude of exercise training effects on arterial function and remodelling. Other studies support the theory that that there may be different time course effects of training on specific vasodilator and constrictor pathways. A new era of understanding of the direct impacts of exercise and training on the vasculature is evolving, and future studies will benefit greatly from technological advances which allow direct characterization of arterial function and structure.

A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans

Non‐Technical Summary  This is the first study, to our knowledge, to use cardiac MRI before and after intensive and closely supervised resistance and endurance exercise training in humans. There is a long held belief that these different forms of training induce ‘concentric’ and ‘eccentric’ adaptation of the heart, but this concept is based on echocardiographic assessments and cross‐sectional comparison of different types of elite athletes. Our findings, using highly sensitive MRI methodology, suggest that concept may need to be reconsidered. This study is of fundamental importance to the understanding of the impact of exercise on human cardiac morphology and physiology.

Vascular adaptation in athletes: is there an 'athlete's artery'?

Whilst the existence of a specific phenotype characterized as ‘athletes heart’ is generally acknowledged, the question of whether athletes exhibit characteristic vascular adaptations has not been specifically addressed. To do so in this symposium, studies which have assessed the size, wall thickness and function of elastic, large muscular and smaller resistance arteries in athletes have been reviewed. Notwithstanding the caveats pertaining to cross‐sectional comparisons between athletes and ‘matched’ control subjects, these studies reveal increased conduit artery size, including enlargement of epicardial arteries and those supplying skeletal muscle. Evidence that peak limb blood flow responses are enhanced in athletes further suggests that resistance arteries undergo increases in total cross‐sectional area. Such increases can be localized to those arteries supplying active muscle leading to speculation, supported by exercise training studies in humans and animal and cellular data, that arterial enlargement is associated with repetitive episodic increases in arterial shear stress which elicit endothelium‐mediated remodelling. Such structural remodelling at conduit and resistance artery level may play a role in accommodating the substantial increase in cardiac output apparent in endurance athletes; arterial pressure is not increased at rest or during exercise in athletes (versus control subjects). Arterial wall remodelling also occurs in athletes but, in contrast to the impact of shear stress on remodelling of arterial lumenal dimensions, the impact of endurance athletic status on wall thickness may be a systemic, rather than localized, phenomenon. Finally, the question of whether the arteries of athletes exhibit enhanced function is moot. Somewhat paradoxically, measures of conduit and resistance artery endothelial function may not be enhanced, compared with healthy control subjects. This may relate to the inherent difficulty of improving arterial function which is already normal, or the time course and transient nature of functional change. It may also relate to the impact of compensatory structural remodelling, as arterial lumen size and wall thickness both affect functional responsiveness. In summary, there is clear evidence for an impact of athletic status on arterial structure and function, at least with respect to the impact of endurance training. Arterial adaptation may, to some extent, emulate that evident in the hearts of endurance athletes, and it is tempting to speculate that similar mechanisms may be at play.

A prospective randomized longitudinal study involving 6 months of endurance or resistance exercise. Conduit artery adaptation in humans

We compared the effects of 6 months of randomly allocated endurance or resistance training on arterial dimensions. Previous research suggests that arterial size increases with exercise, but this is based on cross‐sectional comparisons or interventions that rarely exceeded 12 weeks. Using high‐resolution ultrasound, we demonstrated arterial size adaptations that are specific to the exercise mode. Resistance exercise increased diameter and function in the brachial artery. Femoral diameter and function increased after endurance exercise. Carotid arterial wall thickness decreased with training, while conduit arterial wall thicknesses remained unchanged. This study directly addressed the question of differential impacts of exercise modality on vascular adaptations of conduit arteries in humans in response to a relatively prolonged training intervention period. We conclude that both endurance and resistance modalities have impacts on arterial size, function and wall thickness in vivo, which would be expected to translate to decreased cardiovascular risk.

The Effect of Exergaming on Vascular Function in Children

OBJECTIVES To assess whether exergaming can induce measurable changes in heart rate (HR), energy expenditure (EE), and flow-mediated dilation (FMD) arterial function in healthy children. STUDY DESIGN Fifteen children (8 males, 10.1 ± 0.7 years, body mass index 17.9 ± 2.4 kg.m(-2)) undertook a graded exercise test and 2 × 15 minute exergaming sessions (Xbox 360-Kinect); high intensity exergaming (HiE, Kinect Sports-200 m Hurdles) and low intensity exergaming (LoE, Kinect Sports-Ten Pin Bowling). Brachial artery FMD, a measure of endothelial function and arterial health, was measured before and immediately after each exergaming intervention. Actihearts were used to measure EE and HR during game play and a physical activity enjoyment scale assessed enjoyment. RESULTS Average HR during HiE (146 ± 11 beats per minute) was greater than during LoE (104 ± 11 beats per minute, P < .05), a pattern reinforced by EE data (HiE 294.6 ± 75.2 J.min(-1).kg(-1), LoE 73.7 ± 44.0 J.min(-1).kg(-1), P < .05). FMD decreased after HiE (P < .05), whereas no change was observed following LoE. Subjects reported no differences in enjoyment between LoE and HiE. CONCLUSION HiE, but not LoE, induced large HR and EE responses that were associated with effects on vascular function. This study suggests that an acute bout of HiE exergaming may provide a substrate for beneficial arterial adaptations in children.

Effect of SR Manipulation on Conduit Artery Dilation in Humans

The impact of manipulating shear stress on conduit artery vasodilation has not been comprehensively described in vivo. We hypothesized that manipulation of SR through the brachial and radial arteries would be associated with corresponding changes in diameter. We performed a series of studies involving the following: (1) leg cycle exercise at increasing intensities (≈70 and 85% maximum heart rate [HRmax]) with simultaneous bilateral measurement of SR in the radial arteries; (2) leg cycle exercise for 30 minutes at 80% HRmax with simultaneous bilateral measurement of velocity and diameter in the brachial arteries; and (3) bilateral forearm heating for 30 minutes with simultaneous bilateral measurement of brachial artery diameter and blood velocity. Cycling and forearm heating interventions were performed in the presence of unilateral cuff inflation throughout the experiment, or starting during the intervention (15 minutes), to manipulate SR responses. Cuff placement was associated with lower radial artery SR responses (cuffed versus uncuffed, 248±49 versus 349±105 L/s 85% HRmax; P<0.01), and diameter responses were similarly attenuated (2.45±0.30 versus 2.78±0.20 mm 85% HRmax; P<0.05). Exercise performed at 80% HRmax in the presence of unilateral cuff inflation also reduced brachial artery SR (cuffed versus uncuffed; 258±107 versus 454±157 L/s; P<0.01) and diameter (3.96±0.39 versus 4.20±0.45 mm). Finally, cuff inflation decreased the impact of forearm heating on brachial SR (cuffed versus uncuffed; 262±97 versus 440±106 L/s; P<0.01) and diameter (4.35±0.54 versus 4.87±0.47 mm; P<0.05). Similar significant differences between the cuffed and uncuffed limbs in SR and diameter were observed when cuff inflation occurred during exercise or heating. Our findings strongly implicate SR as an important stimulus to increase conduit artery diameter in humans.

Why isn't flow-mediated dilation enhanced in athletes?

PURPOSE Studies performed in animals and humans strongly suggest that exercise training and physical activity enhance arterial endothelial function. Studies of athletes have, however, been less definitive. METHODS We recruited a range of Olympic and world class athletes who participate in upper or lower limb predominant activities and examined brachial and superficial femoral artery diameter responses to 5-min ischemia (flow-mediated dilation [FMD]) and glyceryl trinitrate, wall thickness (WT) and wall-to-lumen ratio using Doppler and two-dimensional ultrasound. Subjects were elite male canoe paddlers (n = 12), squash players (n = 13), lower limb dominant athletes (i.e., runners/cyclists/triathletes, n = 13), or age- and sex-matched control subjects (n = 16). RESULTS Athletes demonstrated lower superficial femoral artery FMD than controls (P < 0.05), whereas in the brachial artery, a lower FMD was found in squash players (P < 0.05). Both arteries showed a significant inverse correlation between diameter and FMD (P < 0.05), and a significant inverse relationship was apparent between wall-to-lumen ratio and FMD in the superficial femoral artery (P < 0.05). CONCLUSIONS Although artery FMD was lower in athletes, artery size was larger and WT smaller than controls. The apparent reduction in artery FMD may relate to the profound structural remodeling in the diameter and WT of the conduit arteries of athletes. These findings have implications for the interpretation of FMD data, particularly as it pertains to the effect of athletic endeavor on cardiovascular health.

Cardiac adaptation to acute and chronic participation in endurance sports

The pervasive public health message is that moderate amounts of endurance exercise help maintain optimal health and reduce cardiovascular risk. While not enough people meet national physical activity guidelines, there are some at the opposite end of the activity spectrum who far exceed the recommended ‘dose’ of exercise. The cardiovascular health consequences of single and/or multiple (lifelong) ‘doses’ of high-volume endurance exercise are currently being debated. Recent commentaries, case reports and case series data have posed the question whether you can ‘overdose on exercise’, and that is the focus of this brief review.

Sympathetic nervous system activation, arterial shear rate, and flow-mediated dilation.

The aim of this study was to examine the contribution of arterial shear to changes in flow-mediated dilation (FMD) during sympathetic nervous system (SNS) activation in healthy humans. Ten healthy men reported to our laboratory four times. Bilateral FMD, shear rate (SR), and catecholamines were examined before/after 10-min of -35-mmHg lower body negative pressure (LBNP10). On day 1, localized forearm heating (LBNP10+heat) was applied in one limb to abolish the increase in retrograde SR associated with LBNP. Day 2 involved unilateral cuff inflation to 75 mmHg around one limb to exaggerate the LBNP-induced increase retrograde SR (LBNP10+cuff). Tests were repeated on days 3 and 4, using 30-min interventions (i.e., LBNP30+heat and LBNP30+cuff). LBNP10 significantly increased epinephrine levels and retrograde SR and decreased FMD (all P < 0.05). LBNP10+heat prevented the increase in retrograde SR, whereas LBNP10+cuff further increased retrograde SR (P < 0.05). Heating prevented the decrease in percent FMD (FMD%) after LBNP10 (interaction effect, P < 0.05), whereas cuffing did not significantly exaggerate the decrease in FMD% (interaction effect, P > 0.05). Prolongation of the LBNP stimulus for 30-min normalized retrograde SR, catecholamine levels, and FMD (all P > 0.05). Attenuation of retrograde SR during 30 min (LBNP30+heat) was associated with increased FMD% (interaction effects, P < 0.05), whereas increased retrograde SR (LBNP30+cuff) diminished FMD% (interaction effects, P < 0.05). These data suggest that LBNP-induced SNS stimulation decreases FMD, at least in part due to the impact of LBNP on arterial shear stress. Prolonged LBNP stimulation was not associated with changes in SR or FMD%. Our data support a role for changes in SR to the impact of SNS stimulation on FMD.

Cardiovascular responses to water immersion in humans: Impact on cerebral perfusion

Episodic increases in cerebrovascular perfusion and shear stress may have beneficial impacts on endothelial function that improve brain health. We hypothesized that water immersion to the level of the right atrium in humans would increase cerebral perfusion. We continuously measured, in 9 young (means ± SD, 24.6 ± 2.0 yr) healthy men, systemic hemodynamic variables along with blood flows in the common carotid and middle and posterior cerebral arteries during controlled filling and emptying of a water tank to the level of the right atrium. Mean arterial pressure (80 ± 9 vs. 91 ± 12 mmHg, P < 0.05), cardiac output (4.8 ± 0.7 vs. 5.1 ± 0.6 l/min, P < 0.05) and end-tidal carbon dioxide (PetCO2, 39.5 ± 2.0 vs. 44.4 ± 3.5 mmHg, P < 0.05) increased with water immersion, along with middle (59 ± 6 vs. 64 ± 6 cm/s, P < 0.05) and posterior cerebral artery blood flow velocities (41 ± 9 vs. 44 ± 10 cm/s, P < 0.05). These changes were reversed when the tank was emptied. Water immersion is associated with hemodynamic and PetCO2 changes, which increase cerebral blood velocities in humans. This study provides an evidence base for future studies to examine the potential additive effect of exercise in water on improving cerebrovascular health.