Joaquin U. Gonzales

Age and sex influence the balance between maximal cardiac output and peripheral vascular reserve

We evaluated the influence of age and sex on the relationship between central and peripheral vasodilatory capacity. Healthy men (19 younger, 12 older) and women (17 younger, 17 older) performed treadmill and knee extensor exercise to fatigue on separate days while maximal cardiac output (Q, acetylene uptake) and peak femoral blood flow (FBF, Doppler ultrasound) were measured, respectively. Maximal Q was reduced with age similarly in men (Y: 23.6 +/- 2.7 vs. O: 17.4 +/- 3.5 l/min; P < 0.05) and women (Y: 17.7 +/- 1.9 vs. O: 12.3 +/- 1.6 l/min; P < 0.05). Peak FBF was similar between younger (Y) and older (O) men (Y: 2.1 +/- 0.5 vs. O: 2.2 +/- 0.7 l/min) but was lower in older women compared with younger women (Y: 1.9 +/- 0.4 vs. O: 1.4 +/- 0.4 l/min; P < 0.05). Maximal Q was positively correlated with peak FBF in men (Y: r = 0.55, O: r = 0.74; P < 0.05) but not in women (Y: r = 0.34, O: r = 0.10). Normalization of cardiac output to appendicular muscle mass and peak FBF to quadriceps mass reduced the correlation between these variables in younger men (r = 0.30), but the significant association remained in older men (r = 0.68; P < 0.05), with no change in women. These data suggest that 1) aerobic capacity is associated with peripheral vascular reserve in men but not women, and 2) aging is accompanied by a more pronounced sex difference in this relationship.

Effects of physical activity on vasomotor symptoms: examination using objective and subjective measures.

Objective Physical activity (PA) is essential for successful aging and for the prevention and management of common chronic diseases. The empirical support for the beneficial effects of PA on vasomotor symptoms has, however, been mixed. The purpose of this study was to assess the effects of acute aerobic exercise and daily PA on menopausal vasomotor symptoms. Methods Community-dwelling midlife women (N = 121; age range, 40-60 y) not using hormone therapy were recruited for a 15-day daily diary study. Women completed psychological, cardiorespiratory fitness, body composition, and hormonal status screening followed by a 15-day prospective assessment in a “real-life” setting using a personal digital assistant. Participants also completed a 30-minute moderate-intensity aerobic exercise bout on a treadmill between days 5 and 8. Daily PA was assessed objectively through accelerometry, and all symptomatic women (n = 92) completed two 24-hour Biolog sternal skin conductance recordings of hot flashes (HFs)—one at baseline and one immediately after treadmill exercise. Results Both total objective (P = 0.054) and total subjective (P < 0.05) HFs decreased after the acute exercise bout. At the between-person level, daily PA was not associated with self-reported HFs. However, at the within-person level, performing more moderate physical activity than usual was associated with more self-reported HFs in women with lower fitness levels. Conclusions Moderate aerobic exercise decreases objective and subjective HFs 24 hours after exercise; however, in women with lower fitness levels, more daily moderate PA leads to more self-reported symptoms.

Effect of acetazolamide on respiratory muscle fatigue in humans

Previous studies have demonstrated that carbonic anhydrase inhibition with acetazolamide reduces exercise capacity. The mechanism responsible for this early fatigue is unclear, but may be partly mediated by impaired respiratory muscle function. Inspiratory muscle strength and endurance were assessed in seven healthy men (age 28 ± 5 yrs, ±SD) by measuring maximal inspiratory pressure (MIP) and time to task failure during a constant-load breathing test (CLBT), respectively, under control (CON) and acetazolamide (ACZ; 500 mg/8 h po for 3 days) conditions that were separated by two weeks and randomized between subjects. In addition, MIP was measured before and after moderate-intensity cycling exercise to fatigue while pulmonary gas exchange, plasma pH, and ventilation were measured during exercise. ACZ did not alter pulmonary function (FVC, FEV1, MVV) or MIP measured at rest (CON, -157 ± 47 vs. ACZ, -154 ± 45 cmH(2)O, p>0.05), but decreased time to task failure during the CLBT (CON, 1340 ± 820 vs. ACZ, 698 ± 434 s; p=0.01). Exercise duration during cycling exercise was reduced (p=0.003) with ACZ (1090 ± 254 s) compared to CON (1944 ± 532 s) in the presence of a significantly lower plasma pH and higher ventilation compared to control (p<0.05). Compared to resting values, MIP was reduced (p=0.03) in ACZ but not CON at exhaustion. In conclusion, carbonic anhydrase inhibition with ACZ is associated with impaired respiratory muscle function at rest and following constant load cycling which may contribute to reduced exercise tolerance with carbonic anhydrase inhibition.

Role of retrograde flow in the shear stimulus associated with exercise blood flow

To test the hypothesis that retrograde flow influences the shear stimulus of exercise blood flow, eight healthy men [25·6 ± 3·1 years (SD)] performed 20 min of single‐leg knee‐extension exercise at two contraction velocities: fast (FR, 1·5 m s−1) and slow (SR, 0·4 m s−1). Contraction frequency (30 cpm) and workload (5 kg) were kept constant resulting in a work rate of 15·25 W for both contraction velocities. Common femoral artery diameter and blood velocity were measured at rest and during exercise using ultrasound Doppler. Mean blood flow was not different between contraction velocities while antegrade (2012·4 ± 379·9 versus 1745·6 ± 601·5 ml min−1; P = 0·05) and retrograde (121·7 ± 43·0 versus 11·2 ± 6·6 ml min−1; P<0·001) flows were higher during FR than SR contractions, respectively. Despite the similar mean blood flow response, vascular resistance was lower during FR than SR contractions (0·06 ± 0·01 versus 0·08 ± 0·03 units; P = 0·03) and was closely related to shear rate (pooled data: r = −0·77, P<0·01). Retrograde flow was associated with a lower vascular resistance during exercise (pooled data: r = −0·48, P≤0·05). In addition, calculated oscillatory flow indices were higher during FR than SR contractions and were significantly correlated to retrograde flow, shear rate and vascular resistance. These results indicate that retrograde blood flow influences the shear stimulus of exercise blood flow by enhancing the oscillatory behaviour of flow.

Steps per Day, Daily Peak Stepping Cadence, and Walking Performance in Older Adults

We tested the hypothesis that the intensity of daily ambulation would relate with functional walking capacity in older adults. Forty-three women (n = 25) and men (n = 18) between the ages of 60-78 years wore an accelerometer for measurement of average daily steps and 30-min peak stepping cadence. A 400-m walk test was used to measure walking speed. No sex difference was found for average daily steps (p = .76), average peak cadence (p = .96), or walking speed (p = .89). Daily steps (women: r = .68, p < .01; men: r = .04) and peak cadence (women: r = .81, p < .01; men: r = -.16) were positively correlated with walking speed in women but not in men. After controlling for daily steps, peak cadence remained significantly associated with walking speed in women (partial r = .61, p < .01). Walking intensity during daily ambulation is independently related to functional walking capacity in older adults, albeit this relation may be more significant for women than men.

Relation of femoral diameter, shear rate, and dilatory response to knee extensor exercise.

INTRODUCTION Younger women typically exhibit marked dilation of the common femoral artery (CFA) during knee extensor exercise; this is in apparent contrast to subject groups with larger (men) and/or older (older women) vessels, which on average display much smaller exercise-induced increases in CFA diameter. To gain additional insight into this variation, the present study closely examined within- and between-group relationships among CFA diameter, shear rate, and the magnitude of exercise-induced CFA dilation. METHODS Healthy women (15 younger and 18 older) and men (15 younger and 13 older) performed graded single-leg knee extensor exercise while CFA diameter and blood velocity were measured using Doppler ultrasound. RESULTS Resting CFA diameter was smaller (P < 0.05) in women (younger: 0.71 ± 0.02 cm; older: 0.72 ± 0.02 cm) compared with men (younger: 0.84 ± 0.01 cm; older: 0.97 ± 0.03 cm). Resting CFA diameter was inversely associated with peak shear rate (combined groups: r = -0.83, P < 0.001) and the magnitude of dilation in women (younger: r = -0.82; older: r = -0.73, P < 0.001) and younger men (r = -0.66, P < 0.01) but not in older men (r = -0.17, P = 0.56). The dilatory response of the CFA to graded increases in shear rate showed a continuum across groups best described by a quadratic function (r2 = 0.89). Using piecewise regression modeling, a threshold diameter of 0.79 cm was identified below which diameter is inversely related to the magnitude of CFA dilation but above which little to no dilation was present. CONCLUSIONS The CFA dilates to knee extensor exercise in women and men, the magnitude of which varies because of differences in shear rate across CFA diameters.

Arterial stiffness is higher in older adults with increased perceived fatigue and fatigability during walking

We investigated whether central and/or peripheral arterial stiffness contributes to increased perceived fatigue during walking in mobility-intact older adults. Arterial stiffness of the common carotid artery and superficial femoral artery (SFA) was measured using Doppler-ultrasound in 45 community-dwelling women and men (60-78yrs). The change in perceived fatigue was measured after a fast-pace 400meter walk test. Adults that rated feeling more tired after walking (n=10) had higher SFA stiffness (p<0.01), but not carotid artery stiffness, than adults that reported feeling more energetic after walking (n=22). The change in perceived fatigue rating was normalized to energy expenditure during walking to determine perceived fatigability. Adults were divided into lower and higher perceived fatigability groups (n=22 per group). Carotid artery stiffness was not different between perceived fatigability groups after adjusting for age, sex, body fat, systolic blood pressure, fasting blood glucose, daily physical activity levels, and resting diameter. However, SFA stiffness was significantly elevated in the higher as compared to lower perceived fatigability group (β-index: 20.7±1.3 vs. 15.3±1.4U; p=0.02) after adjusting for the abovementioned variables. Moreover, stepwise regression identified SFA β-index to be an independent predictor of perceived fatigability (r(2)=0.38, p<0.01). These results suggest that peripheral arterial stiffness is independently associated with perceived fatigue and fatigability in older adults.

Gait performance in relation to aortic pulse wave velocity, carotid artery elasticity and peripheral perfusion in healthy older adults

Arterial stiffening is a widely known physiological change that occurs with ageing, but the functional consequences of vascular ageing are unclear. The purpose of this study was to determine whether carotid–femoral pulse wave velocity (PWV), mechanical properties of the carotid and femoral arteries and/or peripheral perfusion was associated with gait performance measured using a 400‐m walk test. Twenty‐one healthy older (68 ± 5 years) adults without cardiovascular disease participated in this study. Applanation tonometry was used to measure PWV, and Doppler ultrasound was used to measure arterial wall properties of the left common carotid and common femoral artery along with femoral blood flow. The median walk distance in the first 2 min of the test was 585 ft, and the overall gait speed was 1·5 m s−1. Gait performance was inversely correlated with PWV (distance: r = ‐0·51; speed: r = −0·48; P<0·05) and carotid artery stiffness index β (distance: r = −0·56; speed: r = −0·51; P<0·05) after adjustment for age, body mass index, waist circumference and systolic blood pressure. No significant correlations were found between gait performance and femoral artery stiffness index β or femoral artery blood flow. These results found higher central arterial stiffness, as assessed by segmental arterial stiffness or local arterial wall properties, is associated with lower gait performance in older adults independent of other confounders.

Does l‐citrulline supplementation improve exercise blood flow in older adults?

What is the central question of this study? Does short‐term supplementation with l‐citrulline in order to increase l‐arginine improve exercise blood flow and peripheral dilatation responses to exercise in older adults? What is the main finding and its importance? l‐Citrulline increased femoral blood flow by 11% and vascular conductance by 14% during lower‐limb exercise in older men, whereas no changes were observed in older women. This modest improvement in bulk muscle blood flow in older men has implications for altering muscle metabolism that may result in enhanced exercise tolerance in older adults.

Calf exercise-induced vasodilation is blunted in healthy older adults with increased walking performance fatigue.

Vascular aging as measured by central arterial stiffness contributes to slow walking speed in older adults, but the impact of age-related changes in peripheral vascular function on walking performance is unclear. The aim of this study was to test the hypothesis that calf muscle-specific vasodilator responses are associated with walking performance fatigue in healthy older adults. Forty-five older (60-78yrs) adults performed a fast-paced 400m walk test. Twelve of these adults exhibited fatigue as defined by slowing of walking speed (≥0.02m/s) measured during the first and last 100m segments of the 400m test. Peak calf vascular conductance was measured following 10min of arterial occlusion using strain-gauge plethysmography. Superficial femoral artery (SFA) vascular conductance response to graded plantar-flexion exercise was measured using Doppler ultrasound. No difference was found for peak calf vascular conductance between adults that slowed walking speed and those that maintained walking speed (p>0.05); however, older adults that slowed walking speed had a lower SFA vascular conductance response to calf exercise (at highest workload: slowed group, 2.4±0.9 vs. maintained group, 3.6±0.9ml/kg/min/mmHg; p<0.01). Moreover, the initial increase in SFA vascular conductance from rest to exercise was positively correlated with the change in walking speed for all adults (rho=0.41, p=0.005). In conclusion, these results suggest that calf exercise hemodynamics are associated with walking performance fatigability in older adults.