PubMed Health⌕ Search

Biomedical subjects

Daniel J Green

Publications and source records attributed to Daniel J Green.

At least 19 recordsLinked to original sources

Anti-tumour necrosis factor-alpha therapy over conventional therapy improves endothelial function in adults with rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with cardiovascular morbidity and mortality and inflammation contributes to related endothelial dysfunction. We aimed to investigate the effect of anti-TNFalpha therapy on endothelial function in subjects with rheumatoid arthritis. We measured flow-mediated (FMD) and GTN-mediated dilation of the brachial artery before and following 36 weeks of anti-TNFalpha therapy in nine RA patients and in a group of RA patients on conventional therapy. Thirty-six weeks of anti-TNFalpha therapy improved FMD relative to those on conventional therapy (8.65 +/- 1.50 vs. 1.70 +/- 1.36%, P = 0.02). No significant changes in GTN responses were evident. Significant improvements in tender (P = 0.03) and swollen (P = 0.02) joint counts, patients' global self-assessment (P = 0.01) and DAS-28 scores (P = 0.04) were observed in the anti-TNFalpha treated group. The addition of anti-TNFalpha treatment to conventional therapy, in those with severe RA, reduces inflammatory symptoms and improves endothelial function, potentially lowering future atherosclerotic risk.

Adult↗

Relationship between changes in brachial artery flow-mediated dilation and basal release of nitric oxide in subjects with Type 2 diabetes.

Assessment of flow-mediated dilation (FMD) after forearm ischemia is widely used as a noninvasive bioassay of stimulated nitric oxide (NO)-mediated conduit artery vasodilator function in vivo. Whether this stimulated endothelial NO function reflects basal endothelial NO function is unknown. To test this hypothesis, retrospective analysis of randomized crossover studies was undertaken in 17 subjects with Type 2 diabetes; 9 subjects undertook an exercise training or control period, whereas the remaining 8 subjects were administered an angiotensin II receptor blocker or placebo. FMD was assessed by using wall tracking of high-resolution brachial artery ultrasound images in response to reactive hyperemia. Resistance vessel basal endothelium-dependent NO function was assessed by using intrabrachial administration of NG-monomethyl-L-arginine (L-NMMA) and plethysmographic assessment of forearm blood flow (FBF). FMD was higher after intervention compared with control/placebo (6.15+/-0.53 vs. 3.81+/-0.72%, P<0.001). There were no significant changes in the FBF responses to L-NMMA. Regression analysis between FMD and L-NMMA responses at entry to the study revealed an insignificant correlation (r=-0.10, P=0.7), and improvements in FMD with the interventions were not associated with changes in the L-NMMA responses (r=-0.04, P=0.9). We conclude that conduit artery-stimulated endothelial NO function (FMD) does not reflect basal resistance vessel endothelial NO function in subjects with Type 2 diabetes.

Brachial Artery↗

Cardiac and vascular adaptations to exercise.

PURPOSE OF REVIEW: To briefly review some recent studies of cardiac and vascular adaptation to acute exercise and exercise training. RECENT FINDINGS: Recent studies have suggested that prolonged strenuous bouts of exercise may be associated with transient impairment in systolic and diastolic function, referred to as 'cardiac fatigue'. Furthermore, some studies have reported increased circulating concentrations of cardiac troponins and brain natriuretic peptide following prolonged endurance exercise, suggestive of possible myocyte damage or impairment. Meanwhile, emerging studies of the effects of exercise training on diastolic function are somewhat conflicting; the discrepancies may relate to variability in study designs, indices selected to represent diastolic function or timing of measurements around training cycles. Finally, recent studies of vascular structure and function confirm established evidence for remodelling of large and small arteries and improvement in vascular function with exercise training. SUMMARY: Emerging evidence suggests that prolonged strenuous exercise may be associated with 'cardiac fatigue' or 'cardiac damage', although the clinical implications remain obscure. Vascular adaptations to training improve vasomotor function and induce arterial enlargement, favouring decreased atherothrombotic risk.

Adaptation, Physiological↗

Effects of training resumption on conduit arterial diameter in elite rowers.

BACKGROUND: Exercise training is a known stimulus for arteriogenesis, but it is unclear whether elite athletes, who exhibit increased conduit vessel diameter at rest, experience further structural vascular adaptations as a result of intense exercise training. METHODS: Cross-sectional comparisons were performed between elite rowers (N = 17), following a respite from training, and eight untrained age- and gender-matched controls to assess the effects of long-term exercise on vessel structure. To determine the impact of the resumption of intensive exercise training on conduit artery structure, measures were repeated following 3 and 6 months of training in the athletes; the controls remained inactive. Conduit vessel structure was assessed, using high-resolution B-mode ultrasound, as brachial artery diameter at rest (BADr) and in response to 5-min (BAD5) and 10-min (BAD10) periods of forearm cuff ischemia. Shear rate profiles were also analyzed following cuff deflation at all time points. RESULTS: At entry, all measures of BAD were greater (all P < 0.05) in the athletes relative to controls (athletes vs controls; BADr 4.47 +/- 0.10 vs 3.84 +/- 0.22 mm; BAD5 4.70 +/- 0.10 vs 4.05 +/- 0.36 mm, and BAD10 4.93 +/- 0.10 vs 4.07 +/- 0.25 mm). Resumption of exercise training caused a further increase in brachial artery diameters in the athletes at 3 months (BADr, 4.71 +/- 0.10 mm, P < 0.01; BAD5 4.94 +/- 0.10 mm, P < 0.05; BAD10 5.12 +/- 0.10 mm, P < 0.001), which were maintained, but not further increased, after 6 months of training. CONCLUSIONS: Athletes exhibit enhanced conduit artery diameters at rest and in response to vasodilator stimuli. Despite this long-term training effect on arterial structure, resumption of training further enhances diameter, an effect that occurs within 3 months.

Adult↗

Do skinfolds accurately assess changes in body fat in obese children and adolescents?

PURPOSE: Obesity is epidemic in Western societies, with rapid rates of increase in the young. Various methods exist for the assessment of body composition, but these have not been compared in obese children and adolescents. This study compared methods of body composition assessment in obese young people to determine whether changes in various measures of body composition as a result of exercise training were correlated. METHODS: Multiple anthropometric measures (weight, height, body mass index (BMI), skinfolds, waist and hip girths) and dual-energy x-ray absorptiometry (DEXA) were undertaken in 38 obese children and adolescents (12.7 +/- 2.1 yr) at baseline and following 8 wk of exercise training. RESULTS: At baseline, there were strong relationships (all P < 0.01) between DEXA total fat and weight (r = 0.83), BMI (r = 0.86), waist girth (r = 0.81), hip girth (r = 0.88), sum of six skinfolds (sum6, r = 0.79), and percent body fat (percent body fat) calculated using a four-skinfold equation (EQ4; r = 0.69). Similar relationships (all P < 0.001) existed between DEXA abdominal fat and weight (r = 0.79), waist girth (r = 0.83), hip girth (r = 0.69), and height (r = 0.71). Neither skinfold sums, nor percent body fat calculated from skinfold equations, were selected as independent predictors of DEXA total or abdominal fat by stepwise hierarchical linear regression. The reductions in DEXA total and abdominal fat following exercise were not predicted by changes in skinfolds or percent body fat calculated from skinfolds. CONCLUSION: These data suggest that body fat derived from skinfold measures is poorly predictive of abdominal and total fat derived from DEXA in obese children and adolescents. This finding highlights the limitations of skinfolds in obese subjects and questions the validity of their use to assess changes in body composition with interventions such as exercise training.

Adolescent↗

Impaired skin blood flow response to environmental heating in chronic heart failure.

AIMS: We examined the thermoregulatory response to heat exposure in patients with chronic heart failure. METHODS AND RESULTS: Skin blood flow (SkBF) was measured in HF subjects and matched controls. Cutaneous vascular conductance (CVC) was calculated from laser-Doppler SkBF and blood pressure. To assess the nitric oxide contribution to thermoregulatory responses, subcutaneous microdialysis membranes were placed beneath the laser-Doppler probes to infuse N(G)-nitro-l-arginine methyl ester (l-NAME), or Ringer's solution. Core (T(C)) and skin temperatures (five sites, T(Sk)) were continuously recorded. Subjects were studied during normothermia then at 38 degrees C, 50%RH within a climate chamber. T(C) and T(Sk) did not differ between HF and controls during normothermia and heating induced similar increases in both groups. During heating, CVC rose in both groups, but significantly less so in HF (HF 43.9+/-7.8 vs. controls 58.0+/-7.5% CVC(max), P<0.05). l-NAME attenuated SkBF responses in the control (58.0+/-7.5 vs. 34.6+/-5.1% CVC(max), P<0.001) and HF subjects (43.9+/-7.8 vs. 27.0+/-2.2% CVC(max), P<0.005), with a larger effect evident in the controls (P<0.05). CONCLUSION: HF patients exhibit impaired thermoregulatory responses to heat exposure. Lower SkBF in HF, which defends blood pressure during heat exposure, also predisposes these subjects to heat intolerance.

Blood Flow Velocity↗

Measuring peripheral resistance and conduit arterial structure in humans using Doppler ultrasound.

The purpose of this study was to establish valid indexes of conduit and resistance vessel structure in humans by using edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, to calculate conduit artery blood flow and diameter continuously across the cardiac cycle. Nine subjects aged 36.7 (9.2) yr underwent, on separate days, assessment of brachial artery blood flow and diameter response to 5-, 10-, and 15-min periods of forearm ischemia in the presence and absence of combined sublingual glyceryl trinitrate (GTN) administration. Two further sessions examined responses to ischemic exercise, one in combination with GTN. The peak brachial artery diameter was observed in response to the combination of ischemic exercise and GTN; a significant difference existed between resting brachial artery diameter and peak brachial artery diameter, indicating that resting diameter may be a poor measure of conduit vessel structure in vivo. Peak brachial artery flow was also observed in response to a combination of forearm ischemia exercise and GTN administration, the response being greater than that induced by periods of ischemia, GTN, or ischemic exercise alone. These data indicate that noninvasive indexes of conduit and resistance vessel structure can be simultaneously determined in vivo in response to a single, brief, stimulus and that caution should be applied in using resting arterial diameter as a surrogate measure of conduit artery structure in vivo.

Adult↗

Reduced ventricular flow propagation velocity in elite athletes is augmented with the resumption of exercise training.

Chronic exercise induces physiological enlargement of the left ventricle ('athlete's heart'), but the effects of current and long-term exercise training on diastolic function have not been investigated. Echocardiography and Doppler imaging were used to assess left ventricular (LV) dimensions and indices of diastolic filling in 22 elite athletes at the end of their 'off-season' (baseline) and, subsequently, following 3 and 6 months of training. Twelve matched controls were also studied at baseline, 3 and 6 months. Compared to controls at baseline, athletes exhibited significantly higher LV mass (235.7 +/- 7.1 g versus 178.1 +/- 14.5 g, P < 0.01) and reduced flow propagation velocity (V(P): 50.21 +/- 1.7 versus 72.2 +/- 3.6 cm s(-1), P < 0.01), a measure of diastolic function. Three months of training further increased LV mass in athletes (253.2 +/- 7.1 g; P < 0.01 versus baseline), and significantly increased their V(P) (66.7 +/- 2.5 cm s(-1); P < 0.05 versus baseline). These trends for increased mass and diastolic filling persisted following 6 months of training (LV mass 249.0 +/- 8.7 g P < 0.05 versus baseline; V(P) 75.7 +/- 3.0 cm s(-1); P < 0.01 versus baseline, and P = 0.01 versus 3 months). This study suggests that following a period of relative inactivity the rate of ventricular relaxation during early diastole may be slowed in athletes who exhibit ventricular hypertrophy, whilst resumption of training increases the speed of ventricular relaxation in the presence of further hypertrophy of the left ventricle.

Adaptation, Physiological↗

The 6-minute walk test does not reliably detect changes in functional capacity of patients awaiting cardiac transplantation.

BACKGROUND: Peak oxygen consumption (Vo(2)peak) is a strong independent predictor of prognosis in patients with severe chronic heart failure (CHF) and is used to guide optimal timing of transplantation. However, its assessment is relatively expensive and time-consuming and requires sophisticated equipment and highly trained personnel. The purpose of this study was to determine whether changes in 6-minute walk test (6WT) distance, a simple, inexpensive potential alternative measure of functional capacity, can predict changes in Vo(2)peak in patients with severe CHF. METHODS: Sixteen subjects (ejection fraction 23+/-2%, Vo(2)peak 16.2+/-1.1 ml kg (-1)min(-1)) underwent repeated 6WT and Vo(2)peak assessments that included familiarization and 4 serial measures, 6 weeks apart (baseline and at Weeks 6, 12 and 18). Analysis compared baseline performance with each subsequent testing occasion. RESULTS: At baseline, mean (+/-SE) VO(2)peak was 16.3+/-1.1 ml kg(-1) min(-1) and 6WT distance was 458+/-21 m. 6WT and Vo(2)peak were strongly correlated at all timepoints (average r=0.82; all p<0.05). However, mixed model analysis, assessing the capacity of the changes seen in 6WT to predict changes in Vo(2)peak, showed no statistical significance (F=0.11; p=0.74). CONCLUSIONS: The 6WT is commonly used to assess functional capacity in patients with heart failure. This study demonstrates that, despite a strong cross-sectional correlation with Vo(2)peak, changes in the 6WT are not a reliable predictor of changes in Vo(2)peak within patients. Therefore, the 6WT has limited utility as a serial measure to assess changes in the clinical status of patients with severe heart failure.

Australia↗

Comparison of forearm blood flow responses to incremental handgrip and cycle ergometer exercise: relative contribution of nitric oxide.

The contribution of endothelium-derived nitric oxide (NO) to exercise hyperaemia remains controversial. Disparate findings may, in part, be explained by different shear stress stimuli as a result of different types of exercise. We have directly compared forearm blood flow (FBF) responses to incremental handgrip and cycle ergometer exercise in 14 subjects (age +/-s.e.m.) using a novel software system which calculates conduit artery blood flow continuously across the cardiac cycle by synchronising automated edge-detection and wall tracking of high resolution B-mode arterial ultrasound images and Doppler waveform envelope analysis. Monomethyl arginine (L-NMMA) was infused during repeat bouts of each incremental exercise test to assess the contribution of NO to hyperaemic responses. During handgrip, mean FBF increased with workload (P < 0.01) whereas FBF decreased at lower cycle workloads (P < 0.05), before increasing at 120 W (P < 0.001). Differences in these patterns of mean FBF response to different exercise modalities were due to the influence of retrograde diastolic flow during cycling, which had a relatively larger impact on mean flows at lower workloads. Retrograde diastolic flow was negligible during handgrip. Although mean FBF was lower in response to cycling than handgrip exercise, the impact of L-NMMA was significant during the cycle modality only (P < 0.05), possibly reflecting the importance of an oscillatory antegrade/retrograde flow pattern on shear stress-mediated release of NO from the endothelium. In conclusion, different types of exercise present different haemodynamic stimuli to the endothelium, which may result in differential effects of shear stress on the vasculature.

Enzyme Inhibitors↗

Effect of exercise training on endothelium-derived nitric oxide function in humans.

Vascular endothelial function is essential for maintenance of health of the vessel wall and for vasomotor control in both conduit and resistance vessels. These functions are due to the production of numerous autacoids, of which nitric oxide (NO) has been the most widely studied. Exercise training has been shown, in many animal and human studies, to augment endothelial, NO-dependent vasodilatation in both large and small vessels. The extent of the improvement in humans depends upon the muscle mass subjected to training; with forearm exercise, changes are restricted to the forearm vessels while lower body training can induce generalized benefit. Increased NO bioactivity with exercise training has been readily and consistently demonstrated in subjects with cardiovascular disease and risk factors, in whom antecedent endothelial dysfunction exists. These conditions may all be associated with increased oxygen free radicals which impact on NO synthase activity and with which NO reacts; repeated exercise and shear stress stimulation of NO bioactivity redresses this radical imbalance, hence leading to greater potential for autacoid bioavailability. Recent human studies also indicate that exercise training may improve endothelial function by up-regulating eNOS protein expression and phosphorylation. While improvement in NO vasodilator function has been less frequently found in healthy subjects, a higher level of training may lead to improvement. Regarding time course, studies indicate that short-term training increases NO bioactivity, which acts to homeostatically regulate the shear stress associated with exercise. Whilst the increase in NO bioactivity dissipates within weeks of training cessation, studies also indicate that if exercise is maintained, the short-term functional adaptation is succeeded by NO-dependent structural changes, leading to arterial remodelling and structural normalization of shear. Given the strong prognostic links between vascular structure, function and cardiovascular events, the implications of these findings are obvious, yet many unanswered questions remain, not only concerning the mechanisms responsible for NO bioactivity, the nature of the cellular effect and relevance of other autacoids, but also such practical questions as the optimal intensity, modality and volume of exercise training required in different populations.

Endothelium, Vascular↗

Vasomotor responses to decreased venous return: effects of cardiac deafferentation in humans.

We compared haemodynamic and peripheral vasomotor responses to lower body negative pressure (LBNP) in cardiac transplant recipients who had undergone bicaval anastomoses, involving right atrial deafferentation (-RA), and the conventional procedure in which some atrial baroreceptor afferents remain intact (+RA). We measured mean forearm blood flow (FBF) responses using Doppler/ultrasound during three randomised trials involving 0 (baseline), -20 and -40 mmHg LBNP in 15 transplant recipients (9 -RA, 6 +RA) and in eight healthy matched controls. A significant effect of LBNP on FBF existed between control and transplant groups (P < 0.05; two-way ANOVA). Mild LBNP (-20 mmHg), significantly decreased FBF by 29.7 +/- 10.0% relative to baseline in +RA subjects (P < 0.05), whereas the 17.7 +/- 10.3% decrease in -RA subjects was not significant. In response to -40 mmHg LBNP, FBF significantly decreased in control (42.4 +/- 4.6%, P < 0.05) and +RA subjects (33.3 +/- 11.4%, P < 0.05) with no significant change in the -RA group. The response of systolic blood pressure (SBP) to -40 mmHg significantly differed between groups (P < 0.05): -RA subjects decreased significantly (P < 0.05) whilst the decrease in SBP in +RA subjects did not achieve significance and control subjects exhibited an increase. The heart rate increase from baseline to -40 mmHg was significantly attenuated in -RA relative to controls and the +RA group (P < 0.05). The present study demonstrates that atrial deafferentation impairs reflex vasomotor control of the circulation in response to low- and high-level LBNP, indicating that atrial deafferentation may contribute to abnormal arterial pressure regulation.

Analysis of Variance↗

Exercise training normalizes vascular dysfunction and improves central adiposity in obese adolescents.

OBJECTIVES: We sought to characterize the impact of obesity on vascular function in adolescents and to determine whether an exercise program reverses abnormalities in endothelial function. BACKGROUND: Obesity, a major modifiable risk factor for cardiovascular disease, is epidemic in Western societies, with rapid rates of increase in the young. Atherosclerosis begins in childhood, and endothelial dysfunction is its earliest detectable manifestation. METHODS: The influence of eight weeks of circuit training (CT) was examined in 19 obese subjects (14.3 +/- 1.5 years), using a randomized, crossover protocol. Functional capacity and muscular strength were assessed by standard techniques. Body composition was examined using anthropometric measures and dual-energy X-ray absorptiometry. Conduit vessel endothelial function was assessed using high-resolution ultrasound and flow-mediated dilation (FMD) of the brachial artery. RESULTS: Circuit training decreased abdominal and trunk fat and significantly improved fitness and muscular strength (p < 0.05). In the obese group, FMD was significantly impaired relative to control subjects (n = 20) at entry (5.3 +/- 0.9% vs. 8.9 +/- 1.5%, p < 0.05) and was normalized after CT (8.8 +/- 0.8%, p < 0.05). CONCLUSIONS: Circuit training improved functional capacity, muscular strength, and body composition in obese adolescents. Furthermore, conduit vessel function was normalized after exercise training. If vascular dysfunction is an integral component of the pathogenesis of vascular disease, this study supports the value of an exercise program in the management of obese adolescents.

Adipose Tissue↗

Comparison of resistance and conduit vessel nitric oxide-mediated vascular function in vivo: effects of exercise training.

Exercise training improves vascular function in subjects with cardiovascular disease and risk factors, but there is mounting evidence these vascular adaptations may be vessel bed specific. We have therefore examined the hypothesis that exercise-induced improvements in conduit vessel function are related to changes in resistance vessel function. Endothelium-dependent and -independent conduit vessel function were assessed by using wall-tracking of high-resolution brachial artery ultrasound images of the response to flow-mediated dilation (FMD) and nitroglycerine [glyceryl trinitrate (GTN)] administration. Resistance vessel endothelium-dependent and -independent function were assessed using intrabrachial administration of acetylcholine (ACh) and nitroprusside (SNP). Randomized crossover studies of 8-wk exercise training were undertaken in untreated hypercholesterolemic (n = 10), treated hypercholesterolemic (n = 10), coronary artery disease (n = 8), and Type 2 diabetic subjects (n = 15). Exercise training significantly enhanced responses to ACh (P < 0.05) and FMD (P < 0.0001). There were no significant changes in either SNP or GTN responses. The correlation between ACh and FMD responses at entry was not significant (r = 0.186; P = 0.231), and training-induced changes in the ACh did not correlate with those in FMD (r = -0.022; P = 0.890). Similarly, no correlation was evident between the SNP and GTN responses at entry (r = -0.010; P = 0.951) or between changes in these variables with training (r = -0.211; P = 0.191). We conclude that, although short-term exercise training improves endothelium-dependent nitric oxide-mediated vascular function in both conduit and resistance vessels, the magnitude of these improvements are unrelated.

Acetylcholine↗

Effects of exercise training on vascular function in obese children.

OBJECTIVES: Atherosclerosis is a disease that begins in childhood; endothelial dysfunction is its earliest detectable manifestation, and primary prevention strategies are likely to be most effective if instituted early. The aim of this study was to characterize the impact of obesity on vascular function in young children and to determine whether an exercise program improves abnormalities in vascular function. STUDY DESIGN: The influence of 8 weeks of exercise training was examined in 14 obese subjects, 8.9 +/- 0.4 years of age, with the use of a randomized crossover protocol. Conduit vessel endothelial function was assessed by means of high-resolution ultrasound and flow-mediated dilation of the brachial artery (FMD). RESULTS: Exercise training did not change subcutaneous fat mass, body weight, or body mass index. FMD in the obese group was significantly impaired relative to matched control subjects at entry (6.00% +/- 0.69% to 12.32% +/- 3.14%, P <.0001). FMD significantly improved with exercise training (7.35% +/- 0.99%, P <.05) in the obese group. CONCLUSIONS: Conduit vessel FMD, a validated surrogate measure of early atherosclerosis, was impaired in obese children but improved as a result of exercise training. This study supports the value of an exercise program in the treatment of obese children in a primary prevention setting.

Analysis of Variance↗

The effect of learning on ventilatory responses to inspiratory threshold loading in COPD.

BACKGROUND: Progressive threshold loading (PTL) is a common test of respiratory muscle endurance. Healthy naive subjects improve endurance with successive exposures to PTL by altering their breathing responses, thus necessitating a familiarization period before reproducible measures can be obtained. This study sought to determine whether a similar "learning effect" is evident in patients with COPD, and what the mechanism of any such effect may be. METHODS: Ten subjects with COPD (FEV1 34+/-13% predicted) underwent PTL on four occasions (>24 h apart). During PTL measurements were obtained of breathing pattern and maximum threshold pressure (Pthmax) achieved. Maximum inspiratory pressure (PImax) was measured on each occasion. RESULTS: Over the four tests PImax improved by 21+/-16% (SD) (P<0.05) and Pthmax by 32+/-21% (P<0.05) with a plateau in these measures achieved by test three. Pthmax/PImax was unchanged, being 61+/-11% at test one and 67+/-12% at test four. In contrast to healthy subjects, PTL was not associated with increased expiratory time or decreased end-expiratory lung volume. CONCLUSIONS: In contrast to PImax and Pthmax, which changed with successive tests, a single measure of the ratio Pthmax/PImax may present a useful guide to the endurance capacity of the respiratory muscles in patients with COPD.

Adaptation, Physiological↗