Exercise intensity and the protection from postprandial vascular dysfunction in adolescents

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this recordBACKGROUND: Acute exercise transiently improves endothelial function, and protects the vasculature from the deleterious effects of a high fat meal (HFM). We sought to identify whether this response is dependent on exercise intensity in adolescents. METHODS: Twenty adolescents (10 male, 14.3 ± 0.3 y) completed three 1-day trials: 1) rest (CON); 2) 8x1 min cycling at 90% peak power with 75s recovery (high-intensity interval exercise; HIIE); 3) cycling at 90% of the gas exchange threshold (moderate-intensity exercise; MIE) one hour before consuming a HFM (1.50 g∙kg(-1) fat). Macrovascular and microvascular endothelial function were assessed before and immediately after exercise, and three hours after the HFM by flow mediated dilation (FMD) and laser Doppler imaging (peak reactive hyperaemia; PRH). RESULTS: FMD and PRH increased one hour after HIIE (P<0.001, ES=1.20 and P=0.048, ES=0.56) but were unchanged after MIE. FMD and PRH were attenuated three hours after the HFM in CON (P<0.001, ES=1.78 and P=0.02, ES=0.59). FMD remained greater three hours after the HFM in HIIE compared to MIE (P<0.001, ES=1.47) and CON (P<0.001, ES=2.54), and in MIE compared to CON (P<0.001, ES=1.40). Compared to CON, PRH was greater three hours after the HFM in HIIE (P=0.02, ES=0.71) and MIE (P=0.02, ES=0.84), with no differences between HIIE and MIE (P=0.72, ES=0.16). Plasma [triacylglycerol] and [total antioxidant status] were not different between trials. CONCLUSIONS: Exercise intensity plays an important role in protecting the vasculature from the deleterious effects of a HFM. Performing HIIE may provide superior vascular benefits than MIE in adolescent groups

Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordVascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (−44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.National Institute of HealthNational Institute for Health Research (NIHR

Brachial artery vasodilatory response and wall shear rate determined by multi-gate Doppler in a healthy young cohort

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Wall shear rate (WSR) is an important stimulus for the brachial artery flow-mediated dilation (FMD) response. However, WSR estimation near the arterial wall by conventional Doppler is inherently difficult. To overcome this limitation, we utilised multi-gate Doppler to accurately determine the WSR stimulus near the vessel wall simultaneously with the FMD response using an integrated FMD system [Ultrasound Advanced Open Platform (ULA-OP)]. Using the system, we aimed to perform a detailed analysis of WSR-FMD response and establish novel WSR parameters in a healthy young population. Data from 33 young healthy individuals (27.5±4.9yrs, 19F) were analysed. FMD was assessed with reactive hyperemia using ULA-OP. All acquired raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The acquired velocity data revealed that non-parabolic flow-profiles within the cardiac cycle and under different flow-states, with heterogeneity between participants. We also identified seven WSR magnitude and four WSR time-course parameters. Among them, WSR area under the curve until its return to baseline was the strongest predictor of the absolute (R2 =0.25) and percentage (R2 =0.31) diameter changes in response to reactive hyperemia. For the first time, we identified mono- and biphasic WSR stimulus patterns within our cohort that produced different magnitudes of FMD response [absolute diameter change: 0.24±0.10mm (monophasic) vs 0.17±0.09mm (biphasic), p<0.05]. We concluded that accurate and detailed measurement of the WSR stimulus is important to comprehensively understand the FMD response and that this advance in current FMD technology could be important to better understand vascular physiology and pathology.This study was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement number IMI/115006 (the SUMMIT consortium), in part by the National Institute of Health Research (NIHR) Exeter Clinical Research Facility, and by the Italian Ministry of University and Research (MIUR, Project PRIN 2010-2011)

Reservoir-Excess Pressure Parameters Independently Predicts Cardiovascular Events in Individuals With Type 2 Diabetes.

The parameters derived from reservoir-excess pressure analysis have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM and whether they would predict cardiovascular events in individuals with T2DM. We studied 306 people with T2DM with cardiovascular disease (CVD; DMCVD, 70.4±7.8 years), 348 people with T2DM but without CVD (diabetes mellitus, 67.7±8.4 years), and 178 people without T2DM or CVD (control group [CTRL], 67.2±8.9 years). Reservoir-excess pressure analysis-derived parameters, including reservoir pressure integral, peak reservoir pressure, excess pressure integral, systolic rate constant, and diastolic rate constant, were obtained by radial artery tonometry. Reservoir pressure integral was lower in DMCVD diabetes mellitus and than CTRL. Peak reservoir pressure was lower, and excess pressure integral was greater in DMCVD diabetes mellitus than and CTRL. Systolic rate constant was lower in a stepwise manner among groups (DMCVD< diabetes mellitus <CTRL). Diastolic rate constant was greater in DMCVD than CTRL. In the subgroup of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9 noncardiovascular causes), and 108 cardiovascular events occurred during a 3-year follow-up period. Logistic regression analysis revealed that reservoir pressure integral (odds ratio, 0.59 [95% CI, 0.45-0.79]) and diastolic rate constant (odds ratio, 1.60 [95% CI, 1.25-2.06]) were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors (both P<0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered reservoir-excess pressure analysis-derived parameters are associated with T2DM. Furthermore, baseline values of reservoir pressure integral and diastolic rate constant independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM

The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS: 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS: People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (β) -0.096, p = <0.008 and -0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (β -0.099; p = 0.006 and -0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (β -0.043; p = 0.3), but not between HbA1c and SNP (β -0.105; p = 0.02). CONCLUSIONS: In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for "advanced disease" than concomitant CVD, although this requires prospective validation.This received support from the Innovative Medicines Initiative Joint Undertaking under the Grant Agreement No. 115006; http://www.imi-summit.eu

The effectiveness of interventions to change six health behaviours: a review of reviews

Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency). Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis. Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities. Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p

The effect of arm training on thermoregulatory responses and calf volume during upper body exercise

The final publication is available at Springer via https://doi.org/10.1007/s00421-014-2842-9.PURPOSE: The smaller muscle mass of the upper body compared to the lower body may elicit a smaller thermoregulatory stimulus during exercise and thus produce novel training-induced thermoregulatory adaptations. Therefore, the principal aim of the study was to examine the effect of arm training on thermoregulatory responses during submaximal exercise. METHODS: Thirteen healthy male participants (Mean ± SD age 27.8 ± 5.0 years, body mass 74.8 ± 9.5 kg) took part in 8 weeks of arm crank ergometry training. Thermoregulatory and calf blood flow responses were measured during 30 min of arm cranking at 60% peak power (W peak) pre-, and post-training and post-training at the same absolute intensity as pre-training. Core temperature and skin temperatures were measured, along with heat flow at the calf, thigh, upper arm and chest. Calf blood flow using venous occlusion plethysmography was performed pre- and post-exercise and calf volume was determined during exercise. RESULTS: The upper body training reduced aural temperature (0.1 ± 0.3 °C) and heat storage (0.3 ± 0.2 J g(-1)) at a given power output as a result of increased whole body sweating and heat flow. Arm crank training produced a smaller change in calf volume post-training at the same absolute exercise intensity (-1.2 ± 0.8% compared to -2.2 ± 0.9% pre-training; P < 0.05) suggesting reduced leg vasoconstriction. CONCLUSION: Training improved the main markers of aerobic fitness. However, the results of this study suggest arm crank training additionally elicits physiological responses specific to the lower body which may aid thermoregulation.Peer reviewedFinal Accepted Versio

DRhoGEF2 Regulates Cellular Tension and Cell Pulsations in the Amnioserosa during Drosophila Dorsal Closure

Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction

Left atrial mechanics and aortic stiffness following high intensity interval training: a randomised controlled study

Purpose: High intensity interval training (HIIT) has been shown to improve important health parameters, including aerobic capacity, blood pressure, cardiac autonomic modulation and left ventricular (LV) mechanics. However, adaptations in left atrial (LA) mechanics and aortic stiffness remain unclear. Methods: Forty-one physically inactive males and females were recruited. Participants were randomised to either a 4-week HIIT intervention (n=21) or 4-week control period (n=20). The HIIT protocol consisted of 3x30-second maximal cycle ergometer sprints with a resistance of 7.5% body weight, interspersed with 2-minutes of active unloaded recovery, 3 times per week. Speckle tracking imaging of the LA and M-Mode tracing of the aorta was performed pre and post HIIT and control period. Results: Following HIIT, there was significant improvement in LA mechanics, including LA reservoir (13.9±13.4%, p=0.033), LA conduit (8.9±11.2%, p=0.023) and LA contractile (5±4.5%, p=0.044) mechanics compared to the control condition. In addition, aortic distensibility (2.1±2.7cm2dyn-1103, p=0.031) and aortic stiffness index (-2.6±4.6, p=0.041) were improved compared to the control condition. In stepwise linear regression analysis, aortic distensibility change was significantly associated with LA stiffness change R2 of 0.613 (p=0.002). Conclusion: A short-term programme of HIIT was associated with a significant improvement in LA mechanics and aortic stiffness. These adaptations may have important health implications and contribute to the improved LV diastolic and systolic mechanics, aerobic capacity and blood pressure previously documented following HIIT