Knee-extensor Exercise Research Articles

Preserved metabolic reserve capacity in skeletal muscle of post‐infarction heart failure patients

It has been proposed that exercise capacity during whole body exercise in post-infarction congestive heart failure (CHF) patients is limited by skeletal muscle function. We therefore investigated the balance between cardiopulmonary and muscular metabolic capacity. CHF patients (n=8) and healthy subjects (HS, n=12) were included. Patients with coronary artery disease (CAD, n=8) were included as a control for medication. All subjects performed a stepwise incremental load test during bicycling (∼24 kg muscle mass), two-legged knee extensor (2-KE) exercise (∼4 kg muscle mass) and one-legged knee extensor (1-KE) exercise (∼2 kg muscle mass). Peak power and peak pulmonary oxygen uptake (VO(2peak) ) increased and muscle-specific VO(2peak) decreased with an increasing muscle mass involved in the exercise. Peak power and VO(2peak) were lower for CHF patients than HS, with values for CAD patients falling between CHF patients and HS. During bicycling, all groups utilized 24-29% of the muscle-specific VO(2peak) as measured during 1-KE exercise, with no difference between the groups. Hence, the muscle metabolic reserve capacity during whole body exercise is not different between CHF patients and HS, indicating that appropriately medicated and stable post-infarction CHF patients are not more limited by intrinsic skeletal muscle properties during whole body exercise than HS.

Vascular reactivity at rest and during exercise in middle-aged obese men: effects of short-term, low-intensity, exercise training

Although increased blood flow (BF) in exercising muscles is thought to be impaired in obese subjects and may contribute to physical inactivity, data are scarce in this regard and the involvement of endothelium dysfunction remains partly hypothetical. A total of 16 middle-aged obese men (body mass index, BMI ≥ 30 kg m(-2)) and 16 normal-weight men (BMI<25 kg m(-2)), matched for age, were recruited. We used ultrasonography to compare intima-media thickness (IMT) and distensibility of the carotid artery, flow-mediated dilation (FMD), nitrate-dependent dilation (NDD) and peak BF during post-ischemic hyperemia in the brachial artery (a conduit artery), and leg BF during knee-extensor exercise (indicative of resistance vessel function) in obese and in normal-weight men. In addition, 10 obese men participated in an 8 week individualized low-intensity training program. Compared with normal-weight men, obese men had higher carotid IMT (0.50 ± 0.01 vs 0.62 ± 0.04 mm, P < 0.05) but lower carotid distensibility (0.26 ± 0.03 vs 0.11 ± 0.03 mm Hg(-1) 10(-2), P < 0.05), FMD (5.7 ± 0.4 vs 3.3 ± 0.5%, P < 0.05) and peak BF during post-ischemic hyperemia (398 ± 52 vs 229 ± 24%, P < 0.05), despite similar maximal shear rate, without NDD differences. Lower limb BF (ml min(-1) 100 g(-1)) increased significantly from rest to maximal exercise in both groups with lower values in obese men (at peak power, 36.9 ± 1.6 vs 31.5+2.2 ml min(-1) 100 g(-1), P < 0.05). Exercise training normalized carotid distensibility (0.14 ± 0.04 before vs 0.23 ± 0.03 mm Hg(-1) 10(-2) after training, P = 0.09) and FMD (2.7 ± 0.4 before vs 4.8 ± 0.5% after training, P < 0.05), but did not improve brachial post-ischemic peak BF or exercising leg BF. In obese men, conduit and resistance vessel reactivity is depressed, but a short-term low-intensity exercise training improves distensibility and endothelium dependent vasodilation in the large conduit artery, but not post ischemic or exercise muscle BF.

Erythrocyte-dependent regulation of human skeletal muscle blood flow: role of varied oxyhemoglobin and exercise on nitrite, S-nitrosohemoglobin, and ATP

The erythrocyte is proposed to play a key role in the control of local tissue perfusion via three O(2)-dependent signaling mechanisms: 1) reduction of circulating nitrite to vasoactive NO, 2) S-nitrosohemoglobin (SNO-Hb)-dependent vasodilatation, and 3) release of the vasodilator and sympatholytic ATP; however, their relative roles in vivo remain unclear. Here we evaluated each mechanism to gain insight into their roles in the regulation of human skeletal muscle blood flow during hypoxia and hyperoxia at rest and during exercise. Arterial and femoral venous hemoglobin O(2) saturation (O(2)Hb), plasma and erythrocyte NO and ATP metabolites, and leg and systemic hemodynamics were measured in 10 healthy males exposed to graded hypoxia, normoxia, and graded hyperoxia both at rest and during submaximal one-legged knee-extensor exercise. At rest, leg blood flow and NO and ATP metabolites in plasma and erythrocytes remained unchanged despite large alterations in O(2)Hb. During exercise, however, leg and systemic perfusion and vascular conductance increased in direct proportion to decreases in arterial and venous O(2)Hb (r(2) = 0.86-0.98; P = 0.01), decreases in venous plasma nitrite (r(2) = 0.93; P < 0.01), increases in venous erythrocyte nitroso species (r(2) = 0.74; P < 0.05), and to a lesser extent increases in erythrocyte SNO (r(2) = 0.59; P = 0.07). No relationship was observed with plasma ATP (r(2) = 0.01; P = 0.99) or its degradation compounds. These in vivo data indicate that, during low-intensity exercise and hypoxic stress, but not hypoxic stress alone, plasma nitrite consumption and formation of erythrocyte nitroso species are associated with limb vasodilatation and increased blood flow in the human skeletal muscle vasculature.

Separate and combined effects of heat stress and exercise on circulatory markers of oxidative stress in euhydrated humans

Combined heat stress, dehydration, and exercise is associated with enhanced oxidative stress in humans, but the separate and combined effects of heat stress and exercise on circulatory markers of oxidative stress without the influence of dehydration remain uncertain. The purpose of this study was to determine the effects of whole body heat stress alone and in combination with exercise on blood markers of oxidative stress in euhydrated humans. Eight males wore a water-perfused suit at rest and during 6min of one-legged knee extensor exercise under control and heat stress conditions while maintaining euhydration. Following the control trial and a 15min resting period, hot water was perfused through the suit in order to increase core, skin, and mean body temperatures by ~1, ~6, and ~2°C, respectively. Blood samples were taken to measure reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD) and plasma isoprostanes. Heat stress alone did not alter GSH, SOD activity, or plasma isoprostanes, but increased GSSG leading to a reduction in the GSH/GSSG ratio. No changes in these variables were observed with exercise alone. Conversely, combined heat stress and exercise increased both GSH and GSSG, decreased SOD activity, but did not alter GSH/GSSG ratio or isoprostanes. In conclusion, these findings suggest that heat stress, independently of dehydration, induces non-radical oxidative stress at rest but not during moderate exercise because an increase in antioxidant defense compensates the heat stress-induced non-radical oxidative stress.

Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

The role of adenosine and contraction for secretion of vascular endothelial growth factor (VEGF) in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted in the thigh muscle of seven male subjects, and dialysate was collected at rest, during infusion of adenosine, and during knee extensor exercise. The dialysate was analyzed for content of VEGF protein and adenosine. The mechanism of VEGF secretion from muscle cells in culture was examined in resting and electrostimulated cells and in response to the adenosine analog NECA and the adenosine A(2A) receptor specific analog CGS-21680. Adenosine receptors A(1), A(2A), and A(2B) were blocked with DPCPX, ZM-241385, and enprofylline, respectively. cAMP-dependent protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) were inhibited by H-89 and PD-98509, respectively. The human experiment showed that adenosine infusion enhanced (P < 0.05) the interstitial concentration of VEGF protein approximately fourfold above baseline. Exercise increased (P < 0.05) the interstitial VEGF concentration approximately sixfold above rest in parallel with an approximately threefold increase in adenosine concentration. In accordance, in cultured muscle cells, NECA and contraction caused secretion of VEGF (P < 0.05). The contraction-induced secretion of VEGF was abolished by the A(2B) antagonist enprofylline and by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells and that the contraction-induced secretion of VEGF protein is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction-induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent, revealing involvement of additional pathways in VEGF secretion.

Sedentary aging increases resting and exercise-induced intramuscular free radical formation

Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 + or - 6 yr) and six aged (71 + or - 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 + or - 62%) and during exercise (+143 + or - 40%), and this was further complemented by a greater increase in alpha-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 + or - 96% and +298 + or - 120%). Lipid hydroperoxides were also elevated at rest (0.190 + or - 0.169 vs. 0.148 + or - 0.071 nmol/mg total protein) and during exercise (0.567 + or - 0.259 vs. 0.320 + or - 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of alpha/beta-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans.

Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans

The purpose of this study was to elucidate the mechanistic bases for the reported reduction in the O(2) cost of exercise following short-term dietary nitrate (NO(3)(-)) supplementation. In a randomized, double-blind, crossover study, seven men (aged 19-38 yr) consumed 500 ml/day of either nitrate-rich beet root juice (BR, 5.1 mmol of NO(3)(-)/day) or placebo (PL, with negligible nitrate content) for 6 consecutive days, and completed a series of low-intensity and high-intensity "step" exercise tests on the last 3 days for the determination of the muscle metabolic (using (31)P-MRS) and pulmonary oxygen uptake (Vo(2)) responses to exercise. On days 4-6, BR resulted in a significant increase in plasma [nitrite] (mean +/- SE, PL 231 +/- 76 vs. BR 547 +/- 55 nM; P < 0.05). During low-intensity exercise, BR attenuated the reduction in muscle phosphocreatine concentration ([PCr]; PL 8.1 +/- 1.2 vs. BR 5.2 +/- 0.8 mM; P < 0.05) and the increase in Vo(2) (PL 484 +/- 41 vs. BR 362 +/- 30 ml/min; P < 0.05). During high-intensity exercise, BR reduced the amplitudes of the [PCr] (PL 3.9 +/- 1.1 vs. BR 1.6 +/- 0.7 mM; P < 0.05) and Vo(2) (PL 209 +/- 30 vs. BR 100 +/- 26 ml/min; P < 0.05) slow components and improved time to exhaustion (PL 586 +/- 80 vs. BR 734 +/- 109 s; P < 0.01). The total ATP turnover rate was estimated to be less for both low-intensity (PL 296 +/- 58 vs. BR 192 +/- 38 microM/s; P < 0.05) and high-intensity (PL 607 +/- 65 vs. BR 436 +/- 43 microM/s; P < 0.05) exercise. Thus the reduced O(2) cost of exercise following dietary NO(3)(-) supplementation appears to be due to a reduced ATP cost of muscle force production. The reduced muscle metabolic perturbation with NO(3)(-) supplementation allowed high-intensity exercise to be tolerated for a greater period of time.

Exercise-Induced Femoral Artery Dilation is Related to Resting Diameter

PURPOSE: To determine the relationship between resting common femoral artery (CFA) diameter and knee extensor exercise-induced dilation in younger and older men and women. METHODS: Women (15 younger, 18 older) and men (15 younger, 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 smallest (P < 0.05) in women (younger: 0.71 ± 0.02 cm; older: 0.72 ± 0.02 cm) as compared to men (younger: 0.84 ± 0.01 cm; older: 0.97 ± 0.03 cm). Exercise-induced dilation was greater (P < 0.05) in younger women (5.9 ± 1.3%) as compared to older women (1.7 ± 0.7%) and men (younger: 1.5 ± 0.5%; older: 0.7 ± 0.3%). The slope of the relationship between CFA dilation and shear rate was similar in younger women and younger men, but significantly reduced in older groups (P < 0.05). Resting CFA diameter was inversely associated with 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 older men (r = -0.17; P = 0.56). Correction of dilation for shear rate did not abolish these relationships. Resting diameter was also inversely related to the slope of the relationship between CFA dilation and shear rate in women (younger: r = -0.61; older: r = -0.55; P = 0.01) and younger men (r = -0.52, P = 0.04) but not older men (r = 0.11, P =0.69). CONCLUSIONS: Resting diameter is an important factor to consider when studying the dilatory response of the CFA to knee extensor exercise.

Arterial Compliance And Responsiveness: Relative Impact Of Menopause And Fitness

PURPOSE: To determine if arterial stiffness and vasodilator responsiveness are different between peri- and early post -menopausal women. METHODS: Women going through the menopausal transition were divided into peri-menopausal (PERI, n=8, 50 ± 1 yrs) and early post-menopausal (n=18, 53 ± 1 yrs) based on self-reported menstrual bleeding history. To determine the influence of fitness level, early post-menopausal women were further divided into average fit (POSTAF, n=9) and low fit (POSTLF, n=9) based on maximal oxygen uptake measured during a graded treadmill test to fatigue. Regional measures of arterial stiffness were assessed using applanation tonometry and femoral artery blood flow response to knee extensor exercise (5W step increases every 3 min, 0-25W) was measured using Doppler ultrasound. RESULTS: Maximal oxygen uptake was similar between PERI and POSTAF (34 ± 1 vs. 33 ± 1 ml/kg/min, respectively), but was lower in POSTLF (25 ± 1 ml/kg/min, P < 0.05). Central arterial stiffness was similar between PERI and POSTAF (1145 ± 76 vs. 1106 ± 78 cm/s), but higher in POSTLF (1327 ± 89 cm/s, P < 0.05 versus POSTAF). Lower-extremity arterial stiffness was not different between PERI and POSTAF (956 ± 26 vs. 902 ± 25 cm/s, P = 0.09), but higher in POSTLF (1018 ± 33 cm/s, P < 0.05 versus POSTAF). Increases in femoral vascular conductance during exercise were similar between PERI and POSTAF (P > 0.05), but lower in POSTLF as compared to POST AF from 15-25W (P < 0.05). CONCLUSIONS: Menopausal status at mid-life has no apparent influence on arterial compliance or femoral vasodilatory responsiveness; however, aerobic fitness modulates these responses in early post-menopausal women.

Sex-specific Effect Of Age On Submaximal Leg Exercise Hemodynamics In Middle-aged Adults

PURPOSE: To examine predictors of the leg hemodynamic response to exercise in middle-aged men and women. METHODS: We measured femoral artery blood flow (FBF; from Doppler-ultrasound derived measurements of diameter and blood velocity), mean arterial pressure (MAP), and femoral vascular conductance (FVC; calculated as the quotient of FBF and MAP) at rest and during five minutes of steady-state single knee-extensor exercise at an ∼ 10 watt (W) workload in healthy men (n=23) and women (n=30) (ages 40-72). Exercising FBF and FVC were normalized to power output achieved during exercise (FBF/W and FVC/W, respectively). Age, maximal quadriceps isometric and isokinetic strength (isokinetic dynamometer), maximal oxygen uptake (VO2max; graded treadmill test to maximal exertion), estimated physical activity (scores from the Paffenbarger Physical Activity Questionnaire), blood pressure, and anthropometric variables (estimated quadriceps muscle mass and body mass index (BMI)) were investigated with stepwise multiple linear regression as predictors of FBF/W and FVC/W in men and women separately. RESULTS: The effect of age on FBF/W and FVC/W was negative and marginally significant in men (p = 0.06 and 0.09, respectively) but highly insignificant in women (p = 0.91 and 0.89, respectively). Exercising FBF/W was predicted by age, BMI, and resting femoral blood flow (p < 0.01) and exercising FVC/W was predicted by age, BMI and resting femoral vascular conductance (p < 0.01) in men. Conversely, both exercising FBF/W and FVC/W were predicted by resting systolic blood pressure and weekly physical activity (Paffenbarger question 6 score) (p < 0.01 and p = 0.01, respectively) in women. CONCLUSIONS: There is sex-specificity in factors mediating exercising leg blood flow and vascular conductance in middle-aged adults. Notably, there is no relation between age and submaximal leg exercise hemodynamics in women across this age range, suggesting that the significant deficits in exercising leg vasodilator responses previously observed in older women may either occur prior to middle-age or be mediated by factors other than chronological age. Research Supported by NIH award 5R01HL081893-03.

Challenging The Heart - Effects Of Exercise, Dehydration And Hyperthermia

The combined stress of prolonged exercise, dehydration and hyperthermia leads to a reduced stroke volume (SV) in humans, yet the precise left ventricular (LV) diastolic and systolic responses remain unclear. This reduction in SV may be underpinned by lower LV strain rates and/or twist rates (LV mechanics), which have been shown to link LV filling with ejection. PURPOSE: To examine diastolic and systolic LV strain and twist rates at rest and during exercise with hyperthermia and progressive levels of dehydration. METHODS: Echocardiographic images were obtained, from seven healthy young men (VO2max 58±8 ml.kg-1.min-1) at rest and during sub-maximal one-legged knee-extensor exercise, to estimate end-diastolic volume (EDV), end-systolic volume (ESV), SV, strain rates, systolic twist rate, diastolic untwisting rate in four experimental conditions: 1) Control (euhydration, core temperature ∼37°C), 2) ∼2% Dehydration (∼38°C), 3) ∼3.5% Dehydration (∼38°C), and 4) after Rehydration (∼37°C). RESULTS: At rest, 3.5% Dehydration significantly reduced EDV and SV by 34±15 and 22±15 ml, respectively (P<0.01). In contrast, peak systolic twist rate increased from 77±21 to 148±35 deg.sec-1 (P<0.01) while peak diastolic untwisting rate tended to increase (P=0.11) and was significantly delayed from 7±3% to 23±8% of diastole (P<0.01). Delayed peak untwisting rate at rest was paralleled by a delay in peak diastolic strain rates (P<0.01). Similar to rest, during exercise, EDV and SV were reduced (32±9 and 23±9 ml, respectively, P<0.01). However, the significant change in twist rate observed at rest with dehydration was not apparent during exercise as LV twist rate was already enhanced during Control exercise and did not increase further with superimposed hyperthermia and dehydration. CONCLUSIONS: Maintained strain rates coupled with reduced EDV and enhanced twist rates suggest that the lowering of SV with dehydration and hyperthermia at rest and during small muscle mass exercise is associated with reductions in LV filling likely due to hypovolemia rather than reduced contractility or LV mechanics. This study was Supported by the Gatorade Sports Science Institute.

Limited Maximal Exercise Capacity in Patients With Chronic Heart Failure: Partitioning the Contributors

This study aimed to assess the factors limiting maximal exercise capacity in patients with chronic heart failure (CHF). Maximal exercise capacity, an important index of health in CHF, might be limited by central and/or peripheral factors; however, their contributions remain poorly understood. We studied oxygen (O2) transport and metabolism at maximal cycle (centrally taxing) and knee-extensor (KE) (peripherally taxing) exercise in 12 patients with CHF and 8 healthy control subjects in normoxia and hyperoxia (100% O2). Peak oxygen uptake (VO2) while cycling was 33% lower in CHF patients than in control subjects. By experimental design, peak cardiac output was reduced during KE exercise when compared with cycling (approximately 35%); although muscle mass specific peak leg VO2was increased equally in both groups (approximately 70%), VO2in the CHF patients was still 28% lower. Hyperoxia increased O2carriage in all cases but only facilitated a 7% increase in peak leg VO2in the CHF patients during cycling, the most likely scenario to benefit from increased O2delivery. Several relationships, peak leg VO2(KE + cycle) to capillary-fiber-ratio and capillaries around a fiber to mitochondrial volume, were similar in both groups (r = 0.6–0.7). Multiple independent observations, including a significant skeletal muscle metabolic reserve, suggest skeletal muscle per se contributes minimally to limiting maximal cycle exercise in CHF or healthy control subjects. However, the consistent attenuation of the convective and diffusive components of O2transport (25% to 30%) in patients with CHF during both cycle and even KE exercise compared with control subjects reveals an underlying peripheral O2transport limitation from blood to skeletal muscle in this pathology.

The effect of fatigue from exercise on human limb position sense

We have previously shown, in a two-limb position-matching task in human subjects, that exercise of elbow flexors of one arm led the forearm to be perceived as more extended, while exercise of knee extensors of one leg led the lower leg to be perceived as more flexed. These findings led us to propose that exercise disturbs position sense because subjects perceive their exercised muscles as longer than they actually are. In order to obtain further support for this hypothesis, in the first experiment reported here, elbow extensors were exercised, with the prediction that the exercised arm would be perceived as more flexed after exercise. The experiment was carried out under three load conditions, with the exercised arm resting on a support, with it supporting its own weight and with it supporting a load of 10% of its voluntary contraction strength. For each condition, the forearm was perceived as more extended, not more flexed, after exercise. This result was confirmed in a second experiment on elbow flexors. Again, under all three conditions the exercised arm was perceived as more extended. To explore the distribution of the phenomenon, in a third experiment finger flexor muscles were exercised. This had no significant effect on position sense at the elbow. In a fourth experiment, position sense at the knee was measured after knee flexors of one leg were exercised and, as for knee extensors, it led subjects to perceive their exercised leg to be more flexed at the knee than it actually was. Putting all the observations together, it is concluded that while the influences responsible for the effects of exercise may have a peripheral origin, their effect on position sense occurs centrally, perhaps at the level of the sensorimotor cortex.

The skeletal muscle VEGF mRNA response to acute exercise in patients with chronic heart failure

In seven patients with chronic heart failure (CHF) and six controls, we examined (a) resting and post-exercise muscle vascular endothelial growth factor (VEGF) mRNA levels and (b) their relationship with muscle structure and function. Muscle biopsies were taken after 30 min of single-leg knee-extensor exercise at 50% of maximum work rate (50% WRmax) from both the exercised and rested legs. Muscle blood flow and O2 uptake were measured during exercise. Resting VEGF mRNA levels were not different between patients and controls and both groups upregulated VEGF mRNA equally in response to acute exercise. Patients had lower , , and mitochondrial density but similar capillarity and fiber area. These findings reveal a normal basal level of muscle VEGF mRNA, its appropriate upregulation in response to acute exercise and, despite increased vascular resistance during exercise, a normal skeletal muscle vascular structure in patients with CHF.

Low blood flow at onset of moderate-intensity exercise does not limit muscle oxygen uptake

The effect of low blood flow at onset of moderate-intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5-min one-legged knee-extensor exercise bout (24 +/- 1 W, mean +/- SD) without (Con) and with (double blockade; DB) arterial infusion of inhibitors of nitric oxide synthase (N(G)-monomethyl-l-arginine) and cyclooxygenase (indomethacin) to inhibit the synthesis of nitric oxide and prostanoids, respectively. Leg blood flow and leg oxygen delivery throughout exercise was 25-50% lower (P < 0.05) in DB compared with Con. Leg oxygen extraction (arteriovenous O(2) difference) was higher (P < 0.05) in DB than in Con (5 s: 127 +/- 3 vs. 56 +/- 4 ml/l), and leg oxygen uptake was not different between Con and DB during exercise. The difference between leg oxygen delivery and leg oxygen uptake was smaller (P < 0.05) during exercise in DB than in Con (5 s: 59 +/- 12 vs. 262 +/- 39 ml/min). The present data demonstrate that muscle blood flow and oxygen delivery can be markedly reduced without affecting muscle oxygen uptake in the initial phase of moderate-intensity exercise, suggesting that blood flow does not limit muscle oxygen uptake at the onset of exercise. Additionally, prostanoids and/or nitric oxide appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise.

Exercise-induced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men

Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 +/- 2 yr; old, 71 +/- 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and alpha-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = approximately 3.0 and approximately 6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = approximately 7.0%) to match the young. KE training also improved exercise-induced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young.

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 consecutive eccentric training at different range of motion on muscle damage and recovery

This study compared two training regimens in which knee extensor exercises were performed at different range of motion. Sixteen males performed bouts of 90 maximal isokinetic eccentric contractions over 6 consecutive days (B1-B6) at either small (n=8) or large (n=8) range of motion. Average of peak torque (Mp) of each of the 90 contraction trials were calculated, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities were measured before, 24 h, 48 h and 6 d after B1. Muscle soreness was evaluated every day during the experiment. At B3 Mp reduced more in group L than in group S. From B1 to B6 group S increased Mp, while in group L Mp did not return to the baseline level. In both groups CK activity elevated 24 h following B1. CK activity was significantly higher in group L 6d after B1. In group L muscle soreness was higher at 48 h, 72 h, 4 d and 5 d after B1. High-intensity, consecutive eccentric knee extensor exercise training at large range of motion may induce greater development of muscle damage and force deficit, than training at small range of motion. Training at small range of motion may induce early adaptation in voluntary torque production.

Higher skeletal muscular metabolic reserve capacity in COPD patients than healthy subjects

We investigated the interaction between skeletal muscle exercise capacity and central restrictions using exercise modalities, which recruit differing levels of muscle mass in eight patients chronic obstructive lung disease (COPD) (FEV(1)% of predicted; 35 [SE 4%]) and eight healthy controls. Subjects performed conventional bicycling, two-leg knee extensor (2-KE) and single-leg knee extensor (1-KE) exercises. Maximal values for pulmonary VO(2) (VO(2max)), power output, blood lactate, heart rate, blood pressure, and arterial oxygen saturation of hemoglobin were registered. VO(2max) in controls was 2453 (210), 1468 (124), and 976 (76) mL/min during bicycling, 2-KE and 1-KE, respectively. The COPD patients achieved 48% (P<0.05), 62% (P<0.05), and 81% (P=0.10) of the control values. The mass-specific VO(2max) (VO(2max)/exercising muscle mass) during 1-KE was 345 (25) and 263 (30) mL/kg/min (P<0.05) in controls and COPD patients, respectively. During 2-KE the controls and COPD patients achieved 85% (4%) and 67% (5%) (P=0.06) of the mass-specific VO(2) during 1-KE, while during bicycling they achieved 31% (2%) and 17% (1%) (P<0.05), respectively. The COPD patients have central restrictions when exercising with a relatively small muscle mass (2-KE) and have a higher muscular metabolic reserve capacity than controls during whole body exercise.

Low Muscle Glycogen and Elevated Plasma Free Fatty Acid Modify but Do Not Prevent Exercise-Induced PDH Activation in Human Skeletal Muscle

OBJECTIVETo test the hypothesis that free fatty acid (FFA) and muscle glycogen modify exercise-induced regulation of PDH (pyruvate dehydrogenase) in human skeletal muscle through regulation of PDK4 expression.RESEARCH DESIGN AND METHODSOn two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relative to the contra-lateral leg (CON) the day before the experimental day. On the experimental days, plasma FFA was ensured normal or remained elevated by consuming breakfast rich (low FFA) or poor (high FFA) in carbohydrate, 2 h before performing 20 min of two-legged knee extensor exercise. Vastus lateralis biopsies were obtained before and after exercise.RESULTSPDK4 protein content was ∼2.2- and ∼1.5-fold higher in LOW than CON leg in high FFA and low FFA, respectively, and the PDK4 protein content in the CON leg was approximately twofold higher in high FFA than in low FFA. In all conditions, exercise increased PDHa (PDH in the active form) activity, resulting in similar levels in LOW leg in both trials and CON leg in high FFA, but higher level in CON leg in low FFA. PDHa activity was closely associated with the PDH-E1α phosphorylation level.CONCLUSIONSMuscle glycogen and plasma FFA attenuate exercise-induced PDH regulation in human skeletal muscle in a nonadditive manner. This might be through regulation of PDK4 expression. The activation of PDH by exercise independent of changes in muscle glycogen or plasma FFA suggests that exercise overrules FFA-mediated inhibition of PDH (i.e., carbohydrate oxidation), and this may thus be one mechanism behind the health-promoting effects of exercise.