Garry A. Tew

Comparison of laser speckle contrast imaging with laser Doppler for assessing microvascular function

OBJECTIVE To compare the inter-day reproducibility of post-occlusive reactive hyperaemia (PORH) and sympathetic vasomotor reflexes assessed by single-point laser Doppler flowmetry (SP-LDF), integrating-probe LDF (IP-LDF) and laser speckle contrast imaging (LSCI), and the spatial variability of PORH assessed by IP-LDF and LSCI. We also evaluated the relationship between IP-LDF and LSCI perfusion values across a broad range of skin blood flows. METHODS Eighteen healthy adults (50% male, age 27 ± 4 years) participated in this study. Using SP-LDF, IP-LDF and LSCI, indices of skin blood flow were measured on the forearm during PORH (1-, 5- and 10-min occlusions) and on the finger pad during inspiratory gasp and cold pressor tests. These tests were repeated 3-7 days later. Data were converted to cutaneous vascular conductance (CVC; laser Doppler flow/mean arterial pressure) and expressed as absolute and relative changes from pre-stimulus CVC (ΔCVC(ABS) and ΔCVC(REL), respectively), as well as normalised to peak CVC for the PORH tests. Reproducibility was expressed as within-subjects coefficients of variation (CV, in %) and intraclass correlation coefficients. RESULTS The reproducibility of PORH on the forearm was poorer when assessed with SP-LDF and IP-LDF compared to LSCI (e.g., CV for 5-min PORH ΔCVC(ABS)=35%, 27% and 19%, respectively), with no superior method of data expression. In contrast, the reproducibility of the inspiratory gasp and cold pressor test responses on the finger pad were better with SP-LDF and IP-LDF compared to LSCI (e.g., CV for inspiratory gasp ΔCVC(REL)=13%, 7% and 19%, respectively). The spatial variability of PORH responses was poorer with IP-LDF compared to LSCI (e.g., CV ranging 11-35% versus 3-16%, respectively). The association between simultaneous LSCI and IP-LDF perfusion values was non-linear. CONCLUSION The reproducibility of cutaneous PORH was better when assessed with LSCI compared to SP-LDF and IP-LDF; probably due to measuring larger skin areas (lower inter-site variability). However, when measuring sympathetic vasomotor reflexes on the finger pad, reproducibility was better with SP-LDF and IP-LDF, perhaps due to the high sensitivity of LSCI to changes in skin blood flow at low levels.

Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: A double-blind randomized controlled feasibility study

BACKGROUND This study assessed the feasibility of a 12-week program of exercise, with and without intramuscular testosterone supplementation, in male patients with chronic heart failure (CHF) and low testosterone status and collected preliminary data for key health outcomes. METHODS Male patients with CHF (n = 41, age 67.2 years, range 51-84 years) with mean ± SD testosterone levels of 10.7 ± 2.6 nmol/L (309 ± 76 ng/dL) were randomly allocated to exercise with testosterone or placebo groups. Feasibility was assessed in terms of recruitment, intervention compliance, and attrition. Outcomes included an incremental shuttle walk test, peak oxygen uptake, muscular strength, echocardiographic measures, N-terminal pro-brain natriuretic peptide, inflammatory markers, depression (Beck Depression Inventory), and health-related quality of life (Minnesota Living with Heart Failure Questionnaire and Medical Outcomes Study Short-Form). RESULTS Attrition was 30% but with 100% compliance to exercise and injections in patients who completed the study. Similar improvements in shuttle walk test (18% vs 19%), body mass (-1.3 kg vs -1.0 kg), and hand grip strength (2.1 kg vs 2.5 kg) from baseline were observed in both groups. The exercise with testosterone group showed improvements from baseline in peak oxygen uptake (P < .01), Beck Depression Inventory (P < .05), leg strength (P < .05), and several Medical Outcomes Study Short-Form quality of life domains (P < .05), which were generally not apparent in the exercise with placebo group. Echocardiographic measures, N-terminal pro-brain natriuretic peptide, and inflammatory markers were mostly unchanged. CONCLUSIONS This study shows for the first time that testosterone supplementation during a program of exercise rehabilitation is feasible and can positively impact on a range of key health outcomes in elderly male patients with CHF who have a low testosterone status.

Limb-specific and cross-transfer effects of arm-crank exercise training in patients with symptomatic peripheral arterial disease.

Arm cranking is a useful alternative exercise modality for improving walking performance in patients with intermittent claudication; however, the mechanisms of such an improvement are poorly understood. The main aim of the present study was to investigate the effects of arm-crank exercise training on lower-limb O2 delivery in patients with intermittent claudication. A total of 57 patients with intermittent claudication (age, 70+/-8 years; mean+/-S.D.) were randomized to an arm-crank exercise group or a non-exercise control group. The exercise group trained twice weekly for 12 weeks. At baseline and 12 weeks, patients completed incremental tests to maximum exercise tolerance on both an arm-crank ergometer and a treadmill. Respiratory variables were measured breath-by-breath to determine peak VO2 (O2 uptake) and ventilatory threshold. Near-IR spectroscopy was used in the treadmill test to determine changes in calf muscle StO2 (tissue O2 saturation). Patients also completed a square-wave treadmill-walking protocol to determine VO2 kinetics. A total of 51 patients completed the study. In the exercise group, higher maximum walking distances (from 496+/-250 to 661+/-324 m) and peak VO2 values (from 17.2+/-2.7 to 18.2+/-3.4 ml.kg-1 of body mass.min-1) were recorded in the incremental treadmill test (P<0.05). After training, there was also an increase in time to minimum StO2 (from 268+/-305 s to 410+/-366 s), a speeding of VO2 kinetics (from 44.7+/-10.4 to 41.3+/-14.4 s) and an increase in submaximal StO2 during treadmill walking (P<0.05). There were no significant changes in the control group. The results suggest that the improvement in walking performance after arm-crank exercise training in patients with intermittent claudication is attributable, at least in part, to improved lower-limb O2 delivery.

Nordic poles immediately improve walking distance in patients with intermittent claudication

OBJECTIVES To investigate the immediate effects of Nordic pole walking (NPW) on walking distance and cardiopulmonary workload in patients with intermittent claudication. METHODS Using a standardised treadmill test (3.2 km h(-1) at 4% gradient), walking distance, cardiopulmonary responses, leg pain and perceived exertion during NPW were compared to responses evoked by normal walking in 20 patients with intermittent claudication. The distance to onset of claudication pain (claudication distance: CD) and to maximum walking distance (MWD), heart rate (HR), expired gas parameters, leg pain (Borgs CR-10 Scale) and perceived exertion (Borgs Rating of Perceived Exertion: RPE Scale) were compared. RESULTS CD increased significantly from a median (range) distance of 77 m (28-503) to 130 m (41-1080) and MWD increased significantly from 206 m (81-1078) to 285 m (107-1080) when patients used the Nordic poles (P=0.000). The level of leg pain at MWD was also significantly reduced during NPW (P=0.002). Perceived exertion at MWD did not increase despite an increase in cardiopulmonary work, as indicated by an increase in oxygen consumption (16.5%; P=0.000). CONCLUSION These results show that NPW immediately enables patients with intermittent claudication to walk further with less pain, despite a higher workload. NPW might also be a useful exercise strategy for improving the cardiovascular fitness of patients with intermittent claudication.

Reproducibility of cutaneous thermal hyperaemia assessed by laser Doppler flowmetry in young and older adults

OBJECTIVES The primary objective of this study was to assess the inter-day reproducibility of cutaneous thermal hyperaemia, as assessed using integrating-probe laser Doppler flowmetry (LDF), in young and older men. A secondary objective was to identify the most reproducible form of data expression. METHODS Cutaneous thermal hyperaemia was assessed on the forearm in 14 young (25±1 year) and 14 older (65±1 year) men, using integrating-probe LDF. The test was repeated 7-14 days later. The baseline, initial peak, and plateau phases of the data traces were identified and expressed as raw cutaneous vascular conductance (CVC), CVC normalised to baseline (%CVC(BL)), and CVC normalised to 44°C vasodilatation (%CVC(MAX)). Reproducibility was assessed using the coefficient of variation (CV) and intraclass correlation coefficient (ICC) statistics. RESULTS The inter-day reproducibility was dependent on how the data were expressed. The reproducibility of the initial peak and plateau was equally acceptable in both young and older adults when data were expressed as %CVC(MAX) (e.g., CVs ranging from 4 to 11%). However, the baseline phase was poorly reproducible in both groups irrespective of the data presentation method used (e.g., CVs ranging from 25 to 35%). Furthermore, expressing data as raw CVC or as %CVC(BL) generally showed poor reproducibility for both groups and all phases of the test (e.g., CVs ranging from 15 to 39%). CONCLUSION Integrating-probe LDF is a reproducible technique to assess cutaneous thermal hyperaemia on the forearm when data are expressed as %CVC(MAX) in healthy young and older adults without history of hypertension or taking system drugs.

Role of sensory nerves in the rapid cutaneous vasodilator response to local heating in young and older endurance‐trained and untrained men

The ability to increase skin blood flow (SkBF) rapidly in response to local heating is diminished with advanced age; however, the mechanisms are unclear. The primary aim of this study was to investigate the role of sensory nerves in this age‐related change. A secondary aim was to investigate the effect of aerobic fitness on sensory nerve‐mediated vasodilatation in young and aged skin. We measured SkBF (using laser Doppler flowmetry) in young and older endurance‐trained and untrained men (n = 7 in each group) at baseline and during 35 min of local skin heating to 42°C at two sites on the ventral forearm. One site was pretreated with topical anaesthetic cream to block local sensory nerve function. Cutaneous vascular conductance (CVC) was calculated as SkBF divided by mean arterial pressure and normalized to maximal values (CVCmax) achieved during local heating to 44°C. At the untreated site, the rapid vasodilatation during the first ∼5 min of local heating (initial peak) was lower in the older untrained group (68 ± 3%CVCmax) compared with all other groups (young trained, 76 ± 4%CVCmax; young untrained, 75 ± 5%CVCmax; and older trained, 81 ± 3%CVCmax; P < 0.05). Sensory nerve blockade abolished these differences among the groups (P > 0.05). The contribution of sensory nerve‐mediated vasodilatation was lower in the older untrained group compared with all other groups (P< 0.05). Our results suggest that the age‐related decline in the rapid vasodilator response to local heating in human skin is explained by diminished sensory nerve‐mediated vasodilatation. These findings also indicate that this age‐related change can be prevented through participation in regular aerobic exercise.

Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves by assessing 1) the age-related decline and 2) the effect of aerobic fitness. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in young (24 ± 1 yr) and older (64 ± 1 yr) endurance-trained and sedentary men (n = 7 per group) at baseline and during 35 min of local skin heating to 42°C at 1) untreated forearm sites, 2) forearm sites treated with bretylium tosylate (BT), which prevents neurotransmitter release from noradrenergic sympathetic nerves, and 3) forearm sites treated with yohimbine + propranolol (YP), which antagonizes α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC = SkBF/mean arterial pressure) and normalized to maximal CVC (%CVC(max)) achieved by skin heating to 44°C. Pharmacological agents were administered using microdialysis. In the young trained group, the rapid vasodilator response was reduced at BT and YP sites (P < 0.05); by contrast, in the young sedentary and older trained groups, YP had no effect (P > 0.05), but BT did (P > 0.05). Neither BT nor YP affected the rapid vasodilator response in the older sedentary group (P > 0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men and nonadrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system.

Endurance Exercise Training in Patients With Small Abdominal Aortic Aneurysm: A Randomized Controlled Pilot Study

OBJECTIVE To investigate the feasibility of endurance exercise training in patients with small abdominal aortic aneurysm (AAA), and to obtain preliminary data of its impact on important health outcomes. DESIGN Randomized controlled pilot study. SETTING University rehabilitation facility. PARTICIPANTS Patients with small AAA (N=28; mean age ± SD, 72±7 y). INTERVENTION Participants were randomized to a 12-week program of moderate-intensity endurance exercise or standard care control (encouragement to exercise only). MAIN OUTCOME MEASURES Safety was assessed in terms of the frequency of adverse events and changes in maximum AAA diameter. Outcomes were assessed at baseline and 12 weeks including cardiopulmonary fitness (ventilatory threshold), health-related quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey [version 2]), and markers of vascular risk (eg, blood pressure and high-sensitivity C-reactive protein). RESULTS Of 545 patients contacted, 28 (5%) entered the trial. There were 3 (11%) dropouts. Adherence to the exercise program was 94%. There were no paradoxical increases in AAA size or adverse clinical events. Ventilatory threshold increased in the exercise group, but not the control group (adjusted mean difference, 2.5 mL·kg(-1)·min(-1); 95% confidence interval, 0.5-4.5; d=.82). Systolic blood pressure and high-sensitivity C-reactive protein decreased in the exercise group compared with the control group (d=.34 and d=.58, respectively). There were no substantial changes in anthropometric variables or quality of life. CONCLUSIONS Despite a low recruitment rate, the findings suggest that moderate-intensity endurance exercise training is feasible in patients with small AAA, and can evoke improvements in important health outcomes.

Exercise training improves cutaneous microvascular endothelial function in post-surgical varicose vein patients

This study investigated the effects of exercise training on cutaneous microvascular function in post-surgical varicose vein patients. Sixteen post-surgical (4-5 weeks) varicose vein patients were randomised to a treadmill-walking exercise group or a non-exercise control group. The exercise group trained twice weekly for 8 weeks. Changes in cutaneous microvascular function of the gaiter area were assessed using laser Doppler flowmetry combined with incremental-dose iontophoretic administration of acetylcholine chloride (ACh) and sodium nitroprusside (SNP) in both supine and standing positions. At 8 weeks, peak flux responses to ACh in the supine position were increased in the exercise group (44+/-30 to 62+/-33 PU; P=0.03) with a similar trend in the standing position (37+/-27 to 74+/-31 PU; P=0.08). There were no such changes in the control group (P>0.05). Additionally, peak flux responses to SNP were unchanged in both groups and body positions (P>0.05). The results suggest that moderate-intensity lower-limb exercise training improves microvascular endothelial vasodilator function in post-surgical varicose vein patients.

Systematic review: height-adjustable workstations to reduce sedentary behaviour in office-based workers

BACKGROUND Time spent sitting in the workplace is an important contributor to overall sedentary risk. Installation of height-adjustable workstations has been proposed as a feasible approach for reducing occupational sitting time in office workers. AIMS To provide an accurate overview of the controlled trials that have evaluated the effects of height-adjustable workstation interventions on workplace sitting time in office-based workers. METHODS A comprehensive search was conducted up until March 2014 in the following databases: Medline, PsychINFO, CENTRAL, EMBASE and PEDro. To identify unpublished studies and grey literature, the reference lists of relevant official or scientific web pages were also checked. Studies assessing the effectiveness of height-adjustable workstations using a randomized or non-randomized controlled design were included. RESULTS The initial search yielded a total of 8497 citations. After a thorough selection process, five studies were included with 172 participants. A formal quality assessment indicated that risk of bias was high in all studies and heterogeneity in interventions and outcomes prevented meta-analysis. Nevertheless, all studies reported that height-adjustable workstation interventions reduced occupational sitting time in office workers. There was insufficient evidence to determine effects on other relevant health outcomes (e.g. body composition, musculoskeletal symptoms, mental health). CONCLUSIONS There is insufficient evidence to make firm conclusions regarding the effects of installing height-adjustable workstations on sedentary behaviour and associated health outcomes in office workers. Larger and longer term controlled studies are needed, which include more representative populations.