Christopher D. Askew

Effect of Ramipril on Walking Times and Quality of Life Among Patients With Peripheral Artery Disease and Intermittent Claudication: A Randomized Controlled Trial

IMPORTANCE Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life. OBJECTIVE To determine the efficacy of ramipril for improving walking ability, patient-perceived walking performance, and quality of life in patients with claudication. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, placebo-controlled trial conducted among 212 patients with peripheral artery disease (mean age, 65.5 [SD, 6.2] years), initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia. INTERVENTION Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. MAIN OUTCOME MEASURES Maximum and pain-free walking times were recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively. RESULTS At 6 months, relative to placebo, ramipril was associated with a 75-second (95% CI, 60-89 seconds) increase in mean pain-free walking time (P < .001) and a 255-second (95% CI, 215-295 seconds) increase in maximum walking time (P < .001). Relative to placebo, ramipril improved the WIQ median distance score by 13.8 (Hodges-Lehmann 95% CI, 12.2-15.5), speed score by 13.3 (95% CI, 11.9-15.2), and stair climbing score by 25.2 (95% CI, 25.1-29.4) (P < .001 for all). The overall SF-36 median Physical Component Summary score improved by 8.2 (Hodges-Lehmann 95% CI, 3.6-11.4; P = .02) in the ramipril group relative to placebo. Ramipril did not affect the overall SF-36 median Mental Component Summary score. CONCLUSIONS AND RELEVANCE Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681226.

EEG activity and mood in health orientated runners after different exercise intensities.

An increasing number of studies within the recent years connected physical exercise with changes in brain cortical activity. Most of this data (1) refers to aerobic exercise and (2) does not correlate to psychological parameters although it is well known that exercise has a positive effect on mood. In times where health activities play a major role it is increasingly necessary to connect somato-physiological and somatopsychological components of physical activity. This study aimed to find changes in EEG activity and mood after low, preferred and high intensity running. EEG and actual state of mood were recorded before and after exercise. Results showed an effect for the preferred and high intensity velocity in both, EEG and mood. As only the higher frequency areas N18 Hz showed persisting decreases post-exercise we concluded that this might be a sign of outlasting effects of exercise on brain cortical activity which may have influences on general well-being. We could also show that there is a clear relationship between EEG activity and mood reflecting a basic principle of cortical excitation.

Primary Motor Cortex Activity is Elevated with Incremental Exercise Intensity

While the effects of exercise on brain cortical activity from pre-to post-exercise have been thoroughly evaluated, few studies have investigated the change in activity during exercise. As such, it is not clear to what extent changes in exercise intensity influence brain cortical activity. Furthermore, due to the difficulty in using brain-imaging methods during complex whole-body movements like cycling, it is unclear to what extent the activity in specific brain areas is altered with incremental exercise intensity over time. Latterly, active electroencephalography (EEG) electrodes combined with source localization methods allow for the assessment of brain activity, measured as EEG current density, within specific cortical regions. The present study aimed to investigate the application of this method during exercise on a cycle ergometer, and to investigate the effect of increasing exercise intensity on the magnitude and location of any changes in electrocortical current density. Subjects performed an incremental cycle ergometer test until subjective exhaustion. Current density of the EEG recordings during each test stage, as well as before and after exercise, was determined. Spatial changes in current density were localized using low-resolution brain electromagnetic tomography (LORETA) to three regions of interest; the primary motor cortex, primary sensory cortex and prefrontal cortex, and were expressed relative to current density within the local lobe. It was demonstrated that the relative current density of the primary motor cortex was intensified with increasing exercise intensity, whereas activity of the primary sensory cortex and that of the prefrontal cortex were not altered with exercise. The results indicate that the combined active EEG/LORETA method allows for the recording of brain cortical activity during complex movements and incremental exercise. These findings indicate that primary motor cortex activity is elevated with incremental exercise intensity during a whole-body movement, like cycling.

What happens to the brain in weightlessness? A first approach by EEG tomography.

Basic changes in environmental conditions are fundamental to understanding brain cortical mechanisms. Several studies have reported impairment of central nervous processes during weightlessness. There is ongoing debate as to whether these impairments are attributable to primary physiological effects or secondary psychological effects of the weightlessness environment. This study evaluates the physiological effects of changed gravity conditions on brain cortical activity. In a first experiment, EEG activity of seven participants was recorded at normal, increased and zero gravity during a parabolic flight. Additionally an EEG under normal gravity conditions preflight was recorded. In a second experiment, 24 participants were exposed to a supine, seated and 9 degree head-down tilt position while EEG was recorded. Data were analysed using low resolution brain electromagnetic tomography (LORETA). Beta-2 EEG activity (18-35 Hz) was found to be increased in the right superior frontal gyrus under normal gravity conditions inflight. By exposure to weightlessness a distinct inhibition of this activity within the same areas could be noticed. As the tilt experiment showed changes in the left inferior temporal gyrus in supine and tilted positions we conclude that the observed changes under weightlessness are not explainable by hemodynamic changes but rather reflect emotional processes related to the experience of weightlessness. These findings suggest that weightlessness has a major impact on electro cortical activity and may affect central nervous and adaptation processes.

The hyperaemic response to passive leg movement is dependent on nitric oxide: a new tool to evaluate endothelial nitric oxide function

Passive leg movement is associated with a ∼3‐fold increase in blood flow to the leg, but the underlying mechanisms remain unknown. Passive leg movement increased venous levels of metabolites of nitric oxide (NO) in young subjects, whereas they remained unaltered in the muscle interstitial space. Inhibition of NO synthesis lowered the vasodilatory response to passive leg movement by ∼90%. The increase in leg blood flow was lower in elderly subjects compared to young subjects and leg blood flow did not increase when passive leg movement was performed by elderly with peripheral artery disease. The results suggest that the hyperaemia induced by passive leg movement is NO dependent. The hyperaemic response to passive leg movement and to ACh was also assessed in elderly subjects and patients with peripheral artery disease.

Effective attacking strategies in rugby union

Abstract Evasive change-of-direction manoeuvres (agility skills) are a fundamental ability in rugby union. In this study, we explored the attributes of agility skill execution as they relate to effective attacking strategies in rugby union. Seven Super 14 games were coded using variables that assessed team patterns and individual movement characteristics during attacking ball carries. The results indicated that tackle-breaks are a key determinant of try-scoring ability and team success in rugby union. The ability of the attacking ball carrier to receive the ball at high speed with at least two body lengths from the defence line against an isolated defender promoted tackle-breaks. Furthermore, the execution of a side-step evasive manoeuvre at a change of direction angle of 20–60° and a distance of one to two body lengths from the defence, and then straightening the running line following the initial direction change at an angle of 20–60°, was associated with tackle-breaks. This study provides critical insight regarding the attributes of agility skill execution that are associated with effective ball carries in rugby union.

Effect of training on the response of plasma vascular endothelial growth factor to exercise in patients with peripheral arterial disease

Expansion of the capillary network, or angiogenesis, occurs following endurance training. This process, which is reliant on the presence of VEGF (vascular endothelial growth factor), is an adaptation to a chronic mismatch between oxygen demand and supply. Patients with IC (intermittent claudication) experience pain during exercise associated with an inadequate oxygen delivery to the muscles. Therefore the aims of the present study were to examine the plasma VEGF response to acute exercise, and to establish whether exercise training alters this response in patients with IC. In Part A, blood was collected from patients with IC (n=18) before and after (+20 and +60 min post-exercise) a maximal walking test to determine the plasma VEGF response to acute exercise. VEGF was present in the plasma of patients (45.11+/-29.96 pg/ml) and was unchanged in response to acute exercise. Part B was a training study to determine whether exercise training altered the VEGF response to acute exercise. Patients were randomly assigned to a treatment group (TMT; n=7) that completed 6 weeks of high-intensity treadmill training, or to a control group (CON; n=6). All patients completed a maximal walking test before and after the intervention, with blood samples drawn as for Part A. Training had no effect on plasma VEGF at rest or in response to acute exercise, despite a significant increase in maximal walking time in the TMT group (915+/-533 to 1206+/-500 s; P=0.009) following the intervention. The absence of a change in plasma VEGF may reflect altered VEGF binding at the endothelium, although this cannot be confirmed by the present data.

Brain and exercise : a first approach using electrotomography

PURPOSE The impact of exercise on brain function has gained broad interest. Because hemodynamic and imaging studies are difficult to perform during and after exercise, electroencephalography (EEG) is often the method of choice. Within this study, we aimed 1) to extend prior work examining changes in scalp-recorded brain electrical activity associated with exercise and 2) to use a distributed source localization algorithm (standardized low-resolution brain electromagnetic tomography [sLORETA]) to model the probable neural sources of changes in EEG activity after exercise. METHODS Electrocortical activity of 22 recreational runners (21-45 yr) was recorded before and after exhaustive treadmill ergometry. Data were analyzed using sLORETA. RESULTS There was an increase in alpha-1 activity (7.5-10 Hz) immediately after exercise, which was localized to the left frontal gyrus (Brodmann area 8). This finding is consistent with alterations in emotional processing. Fifteen minutes after exercise, a decrease in alpha-2 (10-12.5 Hz), beta-1 (12.5-18 Hz), and gamma activities (35-48 Hz) was observed in Brodmann areas 18 and 20-22, which are well known to be involved in language processing. CONCLUSION This study demonstrates that sLORETA is a robust method that allows brain activity maps to be generated from standardized EEG recordings following exercise.

Angiogenic response to passive movement and active exercise in individuals with peripheral arterial disease

Peripheral arterial disease (PAD) is caused by atherosclerosis and is associated with microcirculatory impairments in skeletal muscle. The present study evaluated the angiogenic response to exercise and passive movement in skeletal muscle of PAD patients compared with healthy control subjects. Twenty-one PAD patients and 17 aged control subjects were randomly assigned to either a passive movement or an active exercise study. Interstitial fluid microdialysate and tissue samples were obtained from the thigh skeletal muscle. Muscle dialysate vascular endothelial growth factor (VEGF) levels were modestly increased in response to either passive movement or active exercise in both subject groups. The basal muscle dialysate level of the angiostatic factor thrombospondin-1 protein was markedly higher (P < 0.05) in PAD patients compared with the control subjects, whereas soluble VEGF receptor-1 dialysate levels were similar in the two groups. The basal VEGF protein content in the muscle tissue samples was ∼27% lower (P < 0.05) in the PAD patients compared with the control subjects. Analysis of mRNA expression for a range of angiogenic and angiostatic factors revealed a modest change with active exercise and passive movement in both groups, except for an increase (P < 0.05) in the ratio of angiopoietin-2 to angiopoietin-1 mRNA in the PAD group with both interventions. PAD patients and aged individuals showed a similar limited angiogenic response to active exercise and passive movement. The limited increase in muscle extracellular VEGF combined with an elevated basal level of thrombospondin-1 in muscle extracellular fluid of PAD patients may restrict capillary growth in these patients.

The effect of parabolic flight on perceived physical, motivational and psychological state in men and women: Correlation with neuroendocrine stress parameters and electrocortical activity

Previous findings of decreased mental and perceptual motor performance during parabolic flights have been attributed mainly to the primary effects of weightlessness rather than the accompanying effects of stress and altered mood. Although recent studies have alluded to the possible negative effects of stress on performance, there has been no attempt to investigate this during parabolic flights. Over a period of 3 years, 27 human participants (male n = 18, mean age ± SD 34.67 ± 7.59 years; female n = 9, 36.22 ± 9.92 years) were recruited with the aim to evaluate if, and to what extent, parabolic flights are accompanied by changes in mood. Furthermore, the relationships between mood and physiological markers of stress and arousal, namely circulating stress hormones (ACTH, cortisol, epinephrine, norepinephrine, prolactin and brain activity (EEG)) were investigated. A strong and significant correlation was found between circulating stress hormone concentrations and perceived physical state, motivational state (MOT) and psychological strain (PSYCHO), whereas no interaction between mood and EEG or EEG and stress hormone concentrations was observed. Therefore, two different stress responses appear to be present during parabolic flight. The first seems to be characterised by general cortical arousal, whereas the second seems to evolve from the adrenomedullary system. It is likely that both these mechanisms have different effects on mental and perceptual motor performance, which require further investigation and should to be taken into account when interpreting previous weightlessness research.