Howard H. Carter

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.

Obligatory role of hyperaemia and shear stress in microvascular adaptation to repeated heating in humans.

The endothelium, a single layer of cells lining the entire circulatory system, plays a key role in maintaining vascular health. Endothelial dysfunction independently predicts cardiovascular events and improvement in endothelial function is associated with decreased vascular risk. Previous studies have suggested that exercise training improves endothelial function in macrovessels, a benefit mediated via repeated episodic increases in shear stress. However, less is known of the effects of shear stress modulation in microvessels. In the present study we examined the hypothesis that repeated skin heating improves cutaneous microvascular vasodilator function via a shear stress‐dependent mechanism. We recruited 10 recreationally active males who underwent bilateral forearm immersion in warm water (42°C), 3 times per week for 30 min. During these immersion sessions, shear stress was manipulated in one arm by inflating a pneumatic cuff to 100 mmHg, whilst the other arm remained uncuffed. Vasodilatation to local heating, a NO‐dependent response assessed using laser Doppler, improved across the 8 week intervention period in the uncuffed arm (cutaneous vascular conductance week 0 vs. week 4 at 41°C: 1.37 ± 0.45 vs. 2.0 ± 0.91 units, P= 0.04; 42°C: 2.06 ± 0.45 vs. 2.68 ± 0.83 units; P= 0.04), whereas no significant changes were evident in the cuffed arm. We conclude that increased blood flow, and the likely attendant increase in shear stress, is a key physiological stimulus for enhancing microvascular vasodilator function in humans.

Repeated increases in blood flow, independent of exercise, enhance conduit artery vasodilator function in humans

This study aimed to determine the importance of repeated increases in blood flow to conduit artery adaptation, using an exercise-independent repeated episodic stimulus. Recent studies suggest that exercise training improves vasodilator function of conduit arteries via shear stress-mediated mechanisms. However, exercise is a complex stimulus that may induce shear-independent adaptations. Nine healthy men immersed their forearms in water at 42°C for three 30-min sessions/wk across 8 wk. During each session, a pneumatic pressure cuff was inflated around one forearm to unilaterally modulate heating-induced increases in shear. Forearm heating was associated with an increase in brachial artery blood flow (P<0.001) and shear rate (P<0.001) in the uncuffed forearm; this response was attenuated in the cuffed limb (P<0.005). Repeated episodic exposure to bilateral heating induced an increase in endothelium-dependent vasodilation in response to 5-min ischemic (P<0.05) and ischemic handgrip exercise (P<0.005) stimuli in the uncuffed forearm, whereas the 8-wk heating intervention did not influence dilation to either stimulus in the cuffed limb. Endothelium-independent glyceryl trinitrate responses were not altered in either limb. Repeated heating increases blood flow to levels that enhance endothelium-mediated vasodilator function in humans. These findings reinforce the importance of the direct impacts of shear stress on the vascular endothelium in humans.

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.

Impact of sympathetic nervous system activity on post-exercise flow-mediated dilatation in humans.

Previous studies indicate a transient reduction in arterial function following large muscle group exercise, but the mechanisms involved are unknown. Sympathetic nervous system activation may contribute to such reductions through direct effects in the artery wall, or because of decreases in arterial shear stress. Administration of prazosin (an α1‐adrenoreceptor blocker) abolished the transient reduction in vascular function observed under placebo conditions following exercise. This effect could not be explained by drug‐induced changes in arterial shear stress. These results suggest that sympathetic vasoconstriction directly competes with endothelium‐dependent dilator activity to influence post‐exercise vascular function. These findings have implications for understanding the stimuli responsible for exercise‐induced adaptations in arterial function and health in humans.

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.

Optical coherence tomography in the assessment of acute changes in cutaneous vascular diameter induced by heat stress

There are limited imaging technologies available that can accurately assess or provide surrogate markers of the in vivo cutaneous microvessel network in humans. In this study, we establish the use of optical coherence tomography (OCT) as a novel imaging technique to assess acute changes in cutaneous microvessel area density and diameter in humans. OCT speckle decorrelation images of the skin on the ventral side of the forearm up to a depth of 500 μm were obtained prior to and following 20-25 min of lower limb heating in eight healthy men [30.3 ± 7.6 (SD) yr]. Skin red blood cell flux was also collected using laser Doppler flowmetry probes immediately adjacent to the OCT skin sites, along with skin temperature. OCT speckle decorrelation images were obtained at both baseline and heating time points. Forearm skin flux increased significantly (0.20 ± 0.15 to 1.75 ± 0.38 cutaneous vascular conductance, P < 0.01), along with forearm skin temperature (32.0 ± 1.2 to 34.3 ± 1.0°C, P < 0.01). Quantitative differences in the automated calculation of vascular area densities (26 ± 9 to 49 ± 19%, P < 0.01) and individual microvessel diameters (68 ± 17 to 105 ± 25 μm, P < 0.01) were evident following the heating session. This is the first in vivo within-subject assessment of acute changes in the cutaneous microvasculature in response to heating in humans and highlights the use of OCT as an exciting new imaging approach for skin physiology and clinical research.

Brachial and cerebrovascular functions are enhanced in postmenopausal women after ingestion of chocolate with a high concentration of cocoa

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426.

Does echocardiography accurately reflect CMR-determined changes in left ventricular parameters following exercise training? A prospective longitudinal study

Cardiac adaptation in response to exercise has historically been described using echocardiography. Cardiac magnetic resonance (CMR), however, has evolved as a preferred imaging methodology for cardiac morphological assessment. While direct imaging modality comparisons in athletes suggest that large absolute differences in cardiac dimensions exist, it is currently unknown whether changes in cardiac morphology in response to exercise training are comparable when using echocardiography and CMR. Twenty-two young men were randomly assigned to undertake a supervised and intensive endurance or resistance exercise-training program for 24 wk. Echocardiography and CMR assessment of left ventricular (LV) mass, LV end-diastolic volume, internal cavity dimensions, and wall thicknesses were completed before and after training. At baseline, pooled data for all cardiac parameters were significantly different between imaging methods, while LV mass (r = 0.756, P < 0.001) and volumes (LV end-diastolic volume, r = 0.792, P < 0.001) were highly correlated across modalities. Changes in cardiac morphology data with exercise training were not significantly related when echocardiographic and CMR measures were compared. For example, posterior wall thickness increased by 8.3% (P < 0.05) when assessed using echocardiography, but decreased by 2% when using CMR. In summary, echocardiography and CMR imaging modalities produce findings that differ with respect to changes in cardiac size and volume following exercise training.