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Biomedical subjects

Phillip E Gates

Publications and source records attributed to Phillip E Gates.

15 recordsLinked to original sources
PubMed2006

Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression.

Aging is associated with a decline in vascular endothelial function, manifesting in part as impaired flow-mediated arterial dilation (FMD), but the underlying mechanisms are uncertain. Impaired FMD may be mediated in part by a decrease in synthesis of nitric oxide by endothelial nitric oxide synthase, and in clinical populations this has been attributed to competitive inhibition of l-arginine binding sites by asymmetric dimethylarginine (ADMA). If this mechanism is involved in the age-associated decline in FMD, increasing l-arginine concentration may swing the competitive balance in favor of l-arginine binding, restoring nitric oxide synthesis, and enhancing FMD in older humans. To test this hypothesis, we measured FMD (brachial ultrasound) in 10 younger (21 +/- 1 yr) and 12 older healthy men and women (60 +/- 2 yr) following infusion of vehicle or vehicle + l-arginine. Baseline FMD in the older subjects was only approximately 60% of that in the younger subjects (P = 0.002). l-Arginine did not significantly increase FMD in either group despite 23-fold (older) and 19-fold (younger) increases in plasma l-arginine concentrations (P < 0.0001 vs. control). Protein expression (immunofluorescence) in vascular endothelial cells showed that ADMA and the enzyme isoform that controls its degradation, dimethylarginine dimethylaminohydrolase II, were not different in the younger and older subjects. Endothelium-independent vasodilation (sublingual nitroglycerine) was not different between age groups or conditions. We conclude that acutely increasing plasma concentrations of l-arginine do not significantly improve brachial artery FMD in healthy older subjects and thus does not restore the age-associated loss of FMD. Together with the finding that endothelial cell ADMA protein expression was not increased in older adults, these findings suggest that competitive inhibition of l-arginine binding sites on endothelial nitric oxide synthase by ADMA is not an important mechanism contributing to impaired conduit artery endothelium-dependent dilation with aging in healthy humans.

Adolescent↗
PubMed2006

Modulatory influences on ageing of the vasculature in healthy humans.

Increased arterial stiffness and impaired vascular endothelial function are the two most clinically important events that occur with vascular ageing in humans. Together they contribute to age-associated increases in systolic hypertension, left ventricular remodeling and diastolic dysfunction, coronary artery and other atherosclerotic vascular diseases, congestive heart failure, and the attendant cardiac events such as myocardial infarction. However, there is marked individual variability in arterial stiffness and endothelial function with advancing age, which suggests modulation by one or, more likely, several biological and/or lifestyle factors. Consistent with this idea, habitual aerobic exercise appears to attenuate or completely prevent these adverse changes. Other factors including sex hormone status, circulating total and low-density lipoprotein-cholesterol levels, total body and abdominal fatness, and dietary sodium intake also appear to influence arterial stiffening and endothelial dysfunction with ageing. It is now clear that a number of physiological factors and lifestyle behaviors collectively determine how much and, perhaps in some cases, if functionally or clinically significant vascular ageing occurs in adult humans. Of these, the existing evidence indicates that habitual aerobic exercise may be the single most important modulatory influence.

Aging↗
PubMed2005

Aortic input impedance increases with age in healthy men and women.

Aortic input impedance represents the hydraulic load presented by the systemic circulation to the left ventricle of the heart and is increased in patients with cardiovascular disease. Aging is a strong independent risk factor for cardiovascular disease and could exert this effect partly through an increase in modulus of aortic input impedance. We used a novel noninvasive technique to determine aortic input impedance in 71 healthy men and women aged 20 to 69 years. We found that the aortic input impedance spectrum was shifted rightward with advancing age, characterized by a 37% increase in the frequency of the minimum modulus between the third and seventh decade (P<0.0001). The frequency of the minimum modulus correlated with age in all subjects (r=0.48; P<0.0001), in men (r=0.43; P<0.005), and in women (r=0.53; P=0.001). Although several physical characteristics were associated with the frequency of the minimum modulus (bivariate correlation), a regression model that included age and these physical characteristics showed that age was the only independent predictor of the frequency of the minimum modulus. We conclude that aortic input impedance increases with advancing age in healthy men and women. This increase in aortic input impedance may be an important mechanism by which age increases the risk of cardiovascular disease in humans.

Adult↗
PubMed2005

Fatness is a better predictor of cardiovascular disease risk factor profile than aerobic fitness in healthy men.

BACKGROUND: The prevalence of cardiovascular disease (CVD) is partly attributable to an inactive and/or overweight population. However, the independent association of body fatness and aerobic fitness with CVD risk factors is uncertain. We sought to determine whether fatness or fitness better predicted traditional CVD risk factors in men with broad fatness, aerobic fitness, and age ranges using 3 expressions of adiposity. METHODS AND RESULTS: In 135 carefully screened healthy men, we measured 18 established CVD risk factors, body mass index, total percent body fat, waist circumference, and maximal aerobic capacity. Body mass index, percent body fat, and waist circumference were consistently associated with all metabolic risk factors (r=-0.44 to 0.51, P<0.05) after partialling out the effects of aerobic fitness and age. Body mass index and waist circumference were also independently associated with selective hemodynamic risk factors (r=0.20 to 0.30, P< or =0.01). In contrast, aerobic fitness was independently associated with only selective metabolic risk factors (r=-0.21 to 0.19, P<0.05) and was not associated with any hemodynamic risk factors (P>0.05). Both aerobic fitness and body fatness were independently associated with selective hemostatic risk factors (r=-0.22 to -0.26, P< or =0.01; r=-0.32 to 0.48, P<0.05, respectively). Overall, fatness was more strongly and consistently associated with CVD risk factors than aerobic fitness. CONCLUSIONS: Body fatness is a better predictor of CVD risk factor profile than aerobic fitness in healthy men. Although habitual physical activity is an effective strategy for preventing CVD, elevated body fatness is associated with an adverse CVD risk factor profile independently of aerobic fitness.

Adipose Tissue↗
PubMed2004

Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension.

We determined the temporal effects of dietary sodium restriction on large elastic artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64+/-2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54+/-11 mmol/d, P<0.01) versus baseline (135+/-14). Compared with baseline (0.11+/-0.01 mm/mm Hg), carotid artery compliance was increased by 27% (to 0.14+/-0.02, P<0.05) at the end of week 1 of sodium restriction, attaining peak levels by week 2 (+46%, to 0.16+/-0.02, P<0.01). Similarly, supine resting brachial artery SBP was reduced by >5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (-12 mm Hg, P<0.01 versus baseline). The 24-hour ambulatory SBP was approximately 3 mm Hg lower at week 1 of sodium restriction and approximately 6 mm Hg lower by week 2 (P<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of sodium restriction were strongly related to the corresponding increases in carotid compliance (r=0.80, P<0.01). Urinary sodium excretion, carotid artery compliance, and SBP were not different during normal sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium restriction rapidly improves large elastic artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by sodium restriction in these patients.

Aged↗
PubMed2004

Concentric left ventricular morphology in aerobically trained kayak canoeists.

The aim of the present study was to test the hypothesis that upper body aerobically trained athletes (kayak canoeists) would have greater left ventricular wall thickness, but similar left ventricular diastolic chamber dimensions, compared with recreationally active and sedentary men. Ultrasound echocardiography was used to determine cardiac structure and function in highly trained kayak canoeists (n = 10), moderately active (n = 10) and sedentary men (n = 10). The septal and posterior left ventricular walls were approximately 0.2 cm thicker in kayak canoeists (P < 0.05), and left ventricular mass was 51% and 32% greater (P < 0.05) in canoeists than in the sedentary and moderately trained participants, respectively. There were no differences in left ventricular chamber dimension, suggesting that the kayak canoeists had a concentric pattern of left ventricular adaptation to aerobic upper body training. Scaling the data to body composition indices had no effect on the outcome of the statistical analysis. There were no differences in resting Doppler left ventricular diastolic or systolic function among the groups. Ejection fraction was lower in the kayak canoeists, but the magnitude of the difference was within the normal variability for this measurement. Thus aerobically upper body trained athletes demonstrated a concentric pattern of cardiac enlargement, but resting left ventricle function was not different between athletes, moderately active and sedentary individuals.

Adult↗
PubMed2003

Greater rate of decline in maximal aerobic capacity with age in endurance-trained than in sedentary men.

To determine the relation between habitual endurance exercise status and the age-associated decline in maximal aerobic capacity [i.e., maximal O(2) consumption (Vo(2 max))] in men, we performed a well-controlled cross-sectional laboratory study on 153 healthy men aged 20-75 yr: 64 sedentary and 89 endurance trained. Vo(2 max) (ml. kg(-1). min(-1)), measured by maximal treadmill exercise, was inversely related to age in the endurance-trained (r = -0.80) and sedentary (r = -0.74) men but was higher in the endurance-trained men at any age. The rate of decline in Vo(2 max) with age (ml. kg(-1). min(-1)) was greater (P < 0.001) in the endurance-trained than in the sedentary men. Whereas the relative rate of decline in Vo(2 max) (percent decrease per decade from baseline levels in young adulthood) was similar in the two groups, the absolute rate of decline in Vo(2 max) was -5.4 and -3.9 ml. kg(-1). min(-). decade(-1) in the endurance-trained and sedentary men, respectively. Vo(2 max) declined linearly across the age range in the sedentary men but was maintained in the endurance-trained men until approximately 50 yr of age. The accelerated decline in Vo(2 max) after 50 yr of age in the endurance-trained men was related to a decline in training volume (r = 0.46, P < 0.0001) and was associated with an increase in 10-km running time (r = -0.84, P < 0.0001). We conclude that the rate of decline in maximal aerobic capacity during middle and older age is greater in endurance-trained men than in their sedentary peers and is associated with a marked decline in O(2) pulse.

Adult↗
PubMed2003

Left ventricular structure and diastolic function with human ageing. Relation to habitual exercise and arterial stiffness.

AIMS: We sought to determine if attenuation of the age-associated increase in arterial stiffness by habitual aerobic-endurance exercise would have corresponding effects on left ventricular (LV) structure and diastolic function. METHODS AND RESULTS: We performed a cross-sectional study on 138 young, middle-aged, and older men who were either sedentary, recreationally active, or endurance exercise-trained. Ageing was associated with increased large artery stiffness (aortic pulse wave velocity) and habitual aerobic-endurance exercise was associated with decreased large artery stiffness (lower aortic pulse wave velocity; all P<0.05). Ageing was associated with increased mean LV wall thickness, chamber diameter, mass, concentric remodelling, and a decline in LV diastolic function (all P<0.05). Habitual aerobic-endurance exercise was independently associated with increased LV wall thickness, chamber diameter, and mass (echocardiography; P=0.05 or better). The largest LV mass was seen in older endurance trained men, suggesting an additive effect of exercise training and ageing on the LV. Indices of LV diastolic function declined with age, irrespective of habitual physical activity status. Aortic pulse wave velocity was an independent predictor of concentric LV remodelling in the pooled sample, but did not predict other properties of LV structure and diastolic function. In general, habitual aerobic-endurance exercise status was not uniformly associated with favourable modulation of age-associated changes in LV structure and diastolic function. CONCLUSIONS: We conclude that in contrast to its ability to favourably modulate the stiffness of large elastic arteries, regular aerobic-endurance exercise does not consistently modulate the changes in LV structure and diastolic function that occur with physiological ageing in men.

Adult↗
PubMed2003

Greater age-related reductions in central arterial compliance in resistance-trained men.

Reductions in the compliance of central arteries exert a number of adverse effects on systemic cardiovascular function and disease risk. Using the cross-sectional study design, we determined the relation between chronic resistance training and carotid arterial compliance. A total of 62 healthy normotensive men, 20 to 39 years of age (young) and 40 to 60 years of age (middle-aged), who were either sedentary or resistance-trained, were studied. In both activity groups, carotid arterial compliance (simultaneous ultrasound and applanation tonometry) was lower (P<0.05) in the middle-aged compared with the young men. There was no significant difference between young sedentary and resistance-trained men. In the middle-aged group, carotid arterial compliance in the resistance-trained men was approximately 30% lower (P<0.01) than their sedentary peers. Femoral artery compliance and arm pulse wave velocity (measures of peripheral artery stiffness) were not different among any groups. Left ventricular hypertrophy index (echocardiography) was greater (P<0.05) in resistance-trained compared with sedentary men and was associated with carotid arterial compliance (r=-0.35; P<0.01). We concluded that (1) resistance training is associated with the smaller central arterial compliance in healthy middle-aged men; (2) age-related reductions in arterial compliance was greater in resistance-trained men than in sedentary men; and (3) the lower arterial compliance in the resistance-trained men is associated with left ventricular hypertrophy. In marked contrast to the beneficial effect of regular aerobic exercise, the present findings are not consistent with the idea that resistance training exerts beneficial influences on arterial wall buffering functions.

Adult↗
PubMed2003

Adiposity contributes to differences in left ventricular structure and diastolic function with age in healthy men.

We sought to examine the influence of adiposity in age-associated changes in the left ventricle (LV) in a cohort of 113 healthy men, aged 20-79 yr, by measuring LV structure and diastolic function (echocardiography), whole body composition, and regional adiposity (dual energy x-ray absorptiometry). Aging was associated with increased levels of adiposity, greater wall thickness to chamber radius ratio, LV concentric remodeling, and reduced LV diastolic function (all P < 0.05). Bivariate correlation analysis showed that mean LV wall thickness, a concentric LV morphology, and diastolic function were related to adiposity (r = -0.63 to 0.51; all P < 0.05). The relation between age and both mean LV wall thickness and concentric remodeling was reduced after controlling for percentage total body fat (by 38% and 54%, respectively), percentage abdominal fat (by 42% and 62%), and the abdominal/thigh fat ratio (by 35% and 46%). The diastolic function-age relation was reduced after controlling for percentage total body fat (by 35%), percentage abdominal fat (by 39%), and the abdominal/thigh fat ratio (by 29%). There were no apparent differences in the contribution of percentage total body fat, percentage abdominal fat, or abdominal/thigh fat to the association between age and LV structure/diastolic function. We conclude that increasing adiposity contributes to the LV remodeling/reduced diastolic function that occurs with aging in healthy men.

Abdomen↗
PubMed2002

Basal leg blood flow in healthy women is related to age and hormone replacement therapy status.

Basal leg blood flow declines with age in healthy men, an effect that is mediated by augmented sympathetic vasoconstriction. However, in women the presence or absence of oestrogen and selective use of hormone replacement therapy (HRT) may alter these relationships with ageing. We studied 103 healthy women: 73 postmenopausal (41 HRT, mean +/- S.E.M. 61 +/- 1 years; 32 no-HRT, 63 +/- 2 years) and 30 premenopausal (29 +/- 1 years). Compared with the premenopausal controls, absolute femoral artery blood flow (duplex ultrasound) was 23 % lower (P < 0.001) in the postmenopausal no-HRT group, but only 13 % lower in the HRT group (P < 0.01). The age and HRT group differences in leg blood flow were consistently associated with differences in leg vascular conductance, but not with femoral artery lumen diameter, leg muscle sympathetic nerve activity or cardiac output (systemic arterial blood flow). Leg fat-free mass was smaller in the postmenopausal groups (P < 0.05). Femoral blood flow normalized for leg fat-free mass was 17 % lower (P < 0.01) in the postmenopausal no-HRT compared with the premenopausal women, but was not different in the postmenopausal HRT and premenopausal groups. Femoral artery shear stress was similar in the postmenopausal HRT and premenopausal women, but was lower in the postmenopausal no-HRT group (P < 0.01). Basal whole-leg blood flow declines with age in healthy, oestrogen-deficient women, a phenomenon that is mediated primarily by reductions in leg vascular conductance. Among postmenopausal women, chronic HRT use is associated with augmented basal leg blood flow and vascular conductance. Leg blood flow normalized for leg fat-free mass is preserved with age in women taking chronic HRT. In contrast to men, differences in leg sympathetic vasoconstrictor nerve activity do not explain group differences in leg blood flow and vascular conductance with ageing in women.

Adult↗
PubMed2002

Concentric adaptation of the left ventricle in response to controlled upper body exercise training.

Upper body exercise has many applications to the rehabilitation and maintenance of cardiovascular health of individuals who are unable to exercise their lower body. The hemodynamic loads of upper body aerobic exercise are characterized by relatively high blood pressure and relatively low venous return. It is not clear how the left ventricle adapts to the specific hemodynamic loads associated with this form of exercise training. The purpose of this study was to measure left ventricular structure and function in previously sedentary men by using echocardiography before and after 12 wk of aerobic arm-crank exercise training (n = 22) or a time control period (n = 22). Arm-crank peak oxygen consumption (in ml x kg(-1) x min(-1)) increased by 16% (P < 0.05) after training, and significant differences (P < 0.05) were found in wall thickness (from 0.86 to 0.99 cm) but not in left ventricular internal dimension in diastole or systole. This suggested a concentric pattern of left ventricular hypertrophy that persisted after scaling to changes in anthropometric characteristics. No differences (P < 0.05) were found for any measurements of resting left ventricular function. We conclude that upper body aerobic exercise training results in a specific left ventricular adaptation that is characterized by increased left ventricular wall thickness but no change in chamber dimension.

Adaptation, Physiological↗
PubMed2002

Absence of training-specific cardiac adaptation in paraplegic athletes.

PURPOSE: The distinctive nature of left ventricular (LV) adaptation reported in able-bodied endurance- and power-trained athletes probably reflects the different hemodynamic loading patterns that occur during acute exercise. The exercise-induced hemodynamic loads in spinal cord injured athletes are different to those in able-bodied counterparts (lower venous return and stroke volume, higher heart rate). We sought to test the hypothesis that wall thickness, but not chamber dimension, would be larger in endurance- and power-trained spinal cord injured athletes compared with sedentary spinal cord injured subjects. METHODS: We undertook resting two-dimensional, motion-mode, and Doppler examinations of 11 power-trained, 10 endurance-trained, and 5 sedentary spinal cord injured volunteers and compared structural and functional LV data by using ANOVA. LV structural data were also analyzed after being scaled to body mass (BM)(0.33). RESULTS: There were no statistically significant differences among groups for any of the LV structural or functional measurements. However, there was a trend for larger mean wall thickness (0.95 +/- 0.12 vs 0.83 +/- 0.10 cm) and left ventricular mass (193 +/- 57 vs 164 +/- 66 g) in athletes compared with sedentary individuals. CONCLUSION: It seems unlikely that endurance and power training elicits distinctive patterns of LV enlargement in spinal cord injured athletes. Small adaptations of the left ventricle may occur with athletic training in the spinal cord injured athlete. Research within this population is complicated by extreme heterogeneity in important physical, physiological, and athletic-related variables.

Adaptation, Physiological↗
PubMedDate not supplied

Impact of aerobic training upon left ventricular morphology and function in pre-pubescent children.

Current knowledge of the impact of training on left ventricular (LV) morphology and function in pre-pubescent children is limited. After ethical approval, 59 pre-pubescent children (mean +/- SD age 10.5 +/- 0.7 years) volunteered for the study. Twenty-five (11 girls) participated in a 12-week progressive, cycle-based aerobic exercise training programme (ET) of three 30-min sessions per week at 80% maximum heart rate (HR) and 34 (15 girls) as matched controls (CON). Pre- and post-training echocardiograms assessed LV structures and function such as LV internal dimension in diastole (LVIDd), LV mass, stroke volume (SV) and early to late LV filling velocity ratio (E:A). Peak VO2 was determined via a modified McMaster protocol. Mixed, two-way ANOVA and multiple linear regression were used to analyse peak VO2 and LV structural/functional data that had been allometrically scaled. A significant interaction for peak VO2 was observed (54 +/- 7 to 55 +/- 6 and 57 +/- 6 to 56 +/- 7 ml/lean body mass (LBM) per min in ET and CON, respectively). A small, but significant, main effect for time was observed for LVIDd over the intervention period (13.9 +/- 1.0 to 14.2 +/- 1.1 and 13.5 +/- 0.9 to 13.8 +/- 1.0 cm.LBM(-0.33) in ET and CON, respectively) that could be attributed to normal growth and development. Similar changes in SV (2.12 +/- 0.45 to 2.24 +/- 0.45 and 1.95 +/- 0.42 to 2.08 +/- 0.44 ml/LBM) and LV mass (2.59 +/- 0.55 to 2.79 +/- 0.69 and 2.45 +/- 0.60 to 2.61 +/- 0.65 g/LBM) were evident (main effect for time p < 0.05). The E:A ratio did not alter in either group. A decrease in resting HR in ET (p < 0.05) suggested a training effect. Multiple regression revealed that post-training resting HR was the only significant predictor of peak VO2 (R2 = 18.2% and 16.9% CON and ET respectively). These data suggest that training in pre-pubescent children does not influence LV morphology and function within the current population. Moreover, the association between LV structure/function and peak VO2 was small. Future work may wish to impose a greater training volume and assess cardiovascular responses in pre-pubescent children.

Anthropometry↗