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Biomedical subjects

D N Proctor

Publications and source records attributed to D N Proctor.

18 recordsLinked to original sources

Reserve capacity for ATP consumption during isometric contraction in human skeletal muscle fibers.

Maximum velocity of the actomyosin ATPase reaction (V(max) ATPase) and ATP consumption rate during maximum isometric activation (ATP(iso)) were determined in human vastus lateralis (VL) muscle fibers expressing different myosin heavy chain (MHC) isoforms. We hypothesized that the reserve capacity for ATP consumption [1 -- (ratio of ATP(iso) to V(max) ATPase)] varies across VL muscle fibers expressing different MHC isoforms. Biopsies were obtained from 12 subjects (10 men and 2 women; age 21--66 yr). A quantitative histochemical procedure was used to measure V(max) ATPase. In permeabilized fibers, ATP(iso) was measured using an NADH-linked fluorometric procedure. The reserve capacity for ATP consumption was lower for fibers coexpressing MHC(2X) and MHC(2A) compared with fibers singularly expressing MHC(2A) and MHC(slow) (39 vs. 52 and 56%, respectively). Tension cost (ratio of ATP(iso) to generated force) also varied with fiber type, being highest in fibers coexpressing MHC(2X) and MHC(2A). We conclude that fiber-type differences in the reserve capacity for ATP consumption and tension cost reflect functional differences such as susceptibility to fatigue.

Adenosine Triphosphatases↗

Reduced submaximal leg blood flow after high-intensity aerobic training.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and blunted splanchnic vasoconstriction. Eight untrained subjects (4 men, 4 women, 23-31 yr) performed high-intensity aerobic training for 9-12 wk. Leg blood flow (femoral vein thermodilution), splanchnic blood flow (indocyanine green clearance), cardiac output (acetylene rebreathing), whole body O(2) uptake (VO(2)), and arterial-venous blood gases were measured before and after training at identical submaximal power outputs (70 and 140 W; upright 2-leg cycling). Training increased (P < 0.05) peak VO(2) (12-36%) but did not significantly change submaximal VO(2) or cardiac output. Leg blood flow during both submaximal power outputs averaged 18% lower after training (P = 0.001; n = 7), but these reductions were not correlated with changes in splanchnic vasoconstriction. Submaximal leg VO(2) was also lower after training. These findings support the hypothesis that aerobic training reduces active muscle blood flow at a given submaximal power output. However, changes in leg and splanchnic blood flow resulting from high-intensity training may not be causally linked.

Adult↗

Relative influence of physical activity, muscle mass and strength on bone density.

In a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years), we evaluated the relationship of bone density assessed at a variety of skeletal sites by dual-energy X-ray absorptiometry (DXA) with various muscle mass estimates obtained also from the DXA scan and with physical activity by interview and strength assessed both subjectively and objectively. All these parameters declined with age as judged from these cross-sectional data. All estimates of total skeletal muscle mass were strongly correlated with bone density at different skeletal sites. Muscle mass, in turn, was correlated with physical activity and hand strength. In multivariate models including these variables, muscle mass was the strongest determinant of bone density, accounting for 6-53% (mean 27%) of the variance at the different skeletal sites. Physical activity (and/or a physical activity x age interaction) was an independent predictor of bone mass in 48% of the site-specific models and accounted for 0.03-39% (mean 10%) of the variance, while hand strength (and/or a hand strength x age interaction) accounted for up to 4% (mean 1%) of the variance as an independent predictor of bone density in a third of the models. Although these variables together accounted for a large proportion of the variance in bone density, other potential predictors were not assessed in these analyses. The dramatic decline in physical activity over life seemed unable to completely explain the age-related loss of bone mass, and additional research is needed to determine whether the relationship of muscle mass with bone density is a direct one or due instead to other factors such as circulating hormone levels.

Absorptiometry, Photon↗

Cardiac output during exercise by the open circuit acetylene washin method: comparison with direct Fick.

An open-circuit (OpCirc) acetylene uptake cardiac output (QT) method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated uptake vs. end-tidal change in acetylene, and OpCirc2 was based on an iterative finite difference modeling method. Six subjects [28-44 yr, peak oxygen consumption (VO(2)) = 120% predicted] performed cycle ergometry exercise to compare QT using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by a 10-min rest, and subsequently subjects exercised at 85-90% of their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%, OpCirc2, 12%, Fick, 10%) but were lower at moderate to high exercise intensities (OpCirc1, 3%, OpCirc2, 3%, Fick, 5%). OpCirc1 and OpCirc2 QT correlated highly with Fick QT (R(2) = 0.90 and 0.89, respectively). There were minimal differences between OpCirc1 and OpCirc2 compared with Fick up to moderate-intensity exercise (<70% peak VO(2)); however, both techniques tended to underestimate Fick at >70% peak VO(2). These differences became significant for OpCirc1 only. Part of the differences between Fick and OpCirc methods at the higher exercise intensities are likely related to inhomogeneities in ventilation and perfusion matching (R(2) = 0.36 for Fick - OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided reproducible, reliable measurements of QT during mild to moderate exercise. However, only OpCirc2 appeared to approximate Fick QT at the higher work intensities.

Acetylene↗

Muscle blood flow during exercise: the limits of reductionism.

This paper attempts to integrate some important concepts about the various mechanisms that are thought to cause blood flow to rise during rhythmic exercise. Mechanisms including the muscle pump, substances released by skeletal muscle, substances transported by blood, and factors released by nerves have been postulated to contribute to the rise in muscle blood flow during exercise. Additionally, the factors that initiate the dilation may not be those which sustain it. Although there is normally a close relationship between contractile activity, metabolic rate, and muscle blood flow, this relationship can be disrupted under a variety of circumstances and the active skeletal muscle overperfused. This delinking of flow and metabolism raises important questions about the nature of the vasodilating substances responsible for the rise in blood flow during exercise. We propose that understanding the mechanisms responsible for the "delinking" of flow and metabolism, along with a more synergistic view of current concepts, can provide new insight into the mechanisms which govern exercise hyperemia.

Blood Flow Velocity↗

Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups.

An estimate of total body muscle mass with dual-energy X-ray absorptiometry (DXA; appendicular muscle mass divided by 0.75) was compared with 24-h urinary creatinine excretion in 59 healthy men and women [20-30 yr (younger), 45-59 yr (middle age), and 60-79 yr (older)] who stayed in a clinical research center for 5 days. Total body water ((2)H(2)O dilution), fat (underwater weighing), bone mineral (DXA), and total body protein mass (based on a 4-compartment model) were also measured. Muscle mass estimates by DXA and creatinine were highly correlated (r = 0.80). However, stepwise multiple regression indicated that a significant amount of additional between-subject variability in DXA-based muscle mass estimates could be explained by total body water. Creatinine excretion, knee extensor strength, and total body protein mass all decreased with age, suggesting a decline in muscle cell mass with aging. However, DXA-based muscle mass and measures of nonfat body mass (i.e., lean body mass by (2)H(2)O and fat-free body mass by underwater weighing) did not change with age. These results indicate that DXA and urinary creatinine excretion give different results regarding the decline in total body muscle mass with aging. The factor(s) responsible for the apparent underestimate of age-related sarcopenia by DXA remain to be fully defined, but changes in body water may be an important contributor.

Absorptiometry, Photon↗

Effects of genetic selection and voluntary activity on the medial gastrocnemius muscle in house mice.

In a previous study, we found that in house mice both genetic selection (10 generations of artificial selection for high voluntary activity on running wheels) and access to running wheels (7-8 weeks) elicited a modest increase in maximal oxygen consumption. Based on these results, we hypothesized that genetic selection would affect the changes in endurance and oxidative capacity of the medial gastrocnemius (MG) muscle induced by wheel access (training response). Wheel access increased the isotonic endurance of the MG in both genetically selected and random-bred (control) mice. However, this exercise-induced improvement in isotonic endurance of the MG was similar between genetically selected and control mice. Wheel access also increased the succinate dehydrogenase activity of MG muscle fibers in both selected and control lines. However, this exercise-induced increase in succinate dehydrogenase activity was comparable between genetically selected and control animals. Taken together, these results indicate that the modest increase in maximal oxygen consumption associated with genetic selection is not reflected by the training-induced changes in oxidative capacity and endurance of MG muscle fibers.

Animals↗

Age-related sarcopenia in humans is associated with reduced synthetic rates of specific muscle proteins.

Sarcopenia of aging is not explained entirely on the basis of age-associated reduced physical activity. Progressive neuromuscular changes and diminishing anabolic hormone levels are thought to contribute to the pathogenesis of sarcopenia. Decline in muscle mass indicates a decline in muscle protein content. Recent studies demonstrated an age-related decline in synthesis rate of mixed muscle proteins, myosin heavy chain and mitochondrial protein. Reductions in myosin heavy chain and mitochondrial protein synthesis rates have been correlated with age-associated decrements in muscle strength and aerobic exercise tolerance, respectively. These changes have been reported as early as 50 y of age and are related to the decline in insulin-like growth factor (IGF)-I, testosterone and dehydroepiandrosterone (DHEA)-sulfate. The declining ability to remodel these important muscle proteins may therefore play a role in the development of muscle wasting, metabolic abnormalities and impaired physical functioning seen in old age.

Aging↗

Influence of age and gender on cardiac output-VO2 relationships during submaximal cycle ergometry.

It is presently unclear how gender, aging, and physical activity status interact to determine the magnitude of the rise in cardiac output (Qc) during dynamic exercise. To clarify this issue, the present study examined the Qc-O2 uptake (Vo2) relationship during graded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups (n = 6-8/group): younger men (20-30 yr), older men (56-72 yr), younger women (24-31 yr), and older women (51-72 yr). Qc (acetylene rebreathing), stroke volume (Qc/heart rate), and whole body Vo2 were measured at rest and during submaximal exercise intensities (40, 70, and approximately 90% of peak Vo2). Baseline resting levels of Qc were 0.6-1.2 l/min less in the older groups. However, the slopes of the Qc-Vo2 relationship across submaximal levels of cycling were similar among all four groups (5.4-5.9 l/l). The absolute Qc associated with a given Vo2 (1.0-2.0 l/min) was also similar among groups. Resting and exercise stroke volumes (ml/beat) were lower in women than in men but did not differ among age groups. However, older men and women showed a reduced ability, relative to their younger counterparts, to maintain stroke volume at exercise intensities above 70% of peak Vo2. This latter effect was most prominent in the oldest women. These findings suggest that neither age nor gender has a significant impact on the Qc-Vo2 relationships during submaximal cycle ergometry among chronically endurance-trained individuals.

Adult↗

Reduced leg blood flow during dynamic exercise in older endurance-trained men.

It is currently unclear whether aging alters the perfusion of active muscles during large-muscle dynamic exercise in humans. To study this issue, direct measurements of leg blood flow (femoral vein thermodilution) and systemic arterial pressure during submaximal cycle ergometry (70, 140, and 210 W) were compared between six younger (Y; 22-30 yr) and six older (O; 55-68 yr) chronically endurance-trained men. Whole body O2 uptake, ventilation, and arterial and femoral venous samples for blood-gas, catecholamine, and lactate determinations were also obtained. Training duration (min/day), estimated leg muscle mass (dual-energy X-ray absorptiometry; Y, 21.5 +/- 1.2 vs. O, 19.9 +/- 0.9 kg), and blood hemoglobin concentration (Y, 14.9 +/- 0.4 vs. O, 14.7 +/- 0.2 g/dl) did not significantly differ (P > 0.05) between groups. Leg blood flow, leg vascular conductance, and femoral venous O2 saturation were approximately 20-30% lower in the older men at each work rate (all P < 0.05), despite similar levels of whole body O2 uptake. At 210 W, leg norepinephrine spillover rates and femoral venous lactate concentrations were more than twofold higher in the older men. Pulmonary ventilation was also higher in the older men at 140 (+24%) and 210 (+39%) W. These results indicate that leg blood flow and vascular conductance during cycle ergometer exercise are significantly lower in older endurance-trained men in comparison to their younger counterparts. The mechanisms responsible for this phenomenon and the extent to which they operate in other groups of older subjects deserve further attention.

Adult↗

Skeletal muscle mass and the reduction of VO2max in trained older subjects.

The role of skeletal muscle mass in the age-associated decline in maximal O2 uptake (VO2max) is poorly defined because of confounding changes in muscle oxidative capacity and in body fat and the difficulty of quantifying active muscle mass during exercise. We attempted to clarify these issues by examining the relationship between several indexes of muscle mass, as estimated by using dual-energy X-ray absorptiometry and treadmill VO2max in 32 chronically endurance-trained subjects from four groups (n = 8/group): young men (20-30 yr), older men (56-72 yr), young women (19-31 yr), and older women (51-72 yr). VO2max per kilogram body mass was 26 and 22% lower in the older men (45.9 vs. 62.0 ml.kg-1.min-1) and older women (40.0 vs. 51.5 ml.kg-1.min-1). These age differences were reduced to 14 and 13%, respectively, when VO2max was expressed per kilogram of appendicular muscle. When appropriately adjusted for age and gender differences in appendicular muscle mass by analysis of covariance, whole body VO2max was 0.50 +/- 0.09 l/min less (P < 0.001) in the older subjects. This effect was similar in both genders. These findings suggest that the reduced VO2max seen in highly trained older men and women relative to their younger counterparts is due, in part, to a reduced aerobic capacity per kilogram of active muscle independent of age-associated changes in body composition, i.e., replacement of muscle tissue by fat. Because skeletal muscle adaptations to endurance training can be well maintained in older subjects, the reduced aerobic capacity per kilogram of muscle likely results from age-associated reductions in maximal O2 delivery (cardiac output and/or muscle blood flow).

Absorptiometry, Photon↗

Cardiovascular and peak VO2 responses to supine exercise: effects of age and training status.

Although stroke volume during exercise is affected by aging and posture, few studies have carefully examined the heart rate, blood pressure, and peak oxygen uptake (VO2) responses of older subjects to supine exercise. The present study examined these responses during graded supine cycling in younger (21-30 yr) and older (51-62 yr) untrained (Treadmill VO2max = 47.0 vs 32.3 ml.kg-1.min-1) and endurance-trained (66.3 vs 52.7 ml.kg-1.min-1) men (N = 6/group). All subjects had lower (P < 0.05) peak VO2 (ml.min-1) and peak heart rate responses during supine cycling compared with treadmill exercise. Additionally, the age-related reduction in peak VO2 (approximately 20-30%) was similar for supine compared with treadmill testing, even when normalized to fat-free leg volume and fat-free mass, respectively. However, at given absolute intensities (VO2) of supine exercise, heart rates were 10-15 beats.min-1 less (P < 0.05) in both older groups. Across relative supine work intensities (% of peak), systolic pressure increased most rapidly in the younger trained and older untrained groups. These findings suggest that the effects of aging on peak VO2 are similar during treadmill and supine exercise in both endurance-trained and untrained men. These data also indicate that the heart rate response to supine exercise is attenuated in healthy older men and contributes to their reduced peak VO2.

Adult↗

Peak calf blood flow estimates are higher with Dohn than with Whitney plethysmograph.

Estimates of calf blood flow with venous occlusion plethysmography vary widely between studies, perhaps due to the use of different plethysmographs. Consequently, we compared calf blood flow estimates at rest and during reactive hyperemia in eight healthy subjects (four men and four women) with two commonly used plethysmographs: the mercury-in-silastic (Whitney) strain gauge and Dohn air-filled cuff. To minimize technical variability, flow estimates were compared with a Whitney gauge and a Dohn cuff on opposite calves before and after 10 min of bilateral femoral arterial occlusion. To account for any differences between limbs, a second trial was conducted in which the plethysmographs were switched. Resting flows did not differ between the plethysmographs (P = 0.096), but a trend toward lower values with the Whitney was apparent. Peak flows averaged 37% lower with the Whitney (27.8 +/- 2.8 ml.dl-1.min-1) than with the Dohn plethysmograph (44.4 +/- 2.8 ml.dl-1.min-1; P < 0.05). Peak flow expressed as a multiple above baseline was also lower with the Whitney (10-fold) than with the Dohn plethysmograph (14.5-fold; P = 0.02). Across all flows at rest and during reactive hyperemia, estimates were highly correlated between the plethysmographs in all subjects (r2 = 0.96-0.99). However, the mean slope for the Whitney-Dohn relationship was only 60 +/- 2%, indicating that over a wide range of flows the Whitney gauge estimate was 40% lower than that for the Dohn cuff. These results demonstrate that the same qualitative results can be obtained with either plethysmograph but that absolute flow values will generally be lower with Whitney gauges.

Adult↗

Contribution of nitric oxide and prostaglandins to reactive hyperemia in human forearm.

We investigated the separate and combined contributions of nitric oxide (NO) and vasodilating prostaglandins as mediators of reactive hyperemia in the human forearm. Forearm blood flow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol (n = 12), measurements were made before and after intra-arterial administration of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) to one forearm. In a separate protocol (n = 7), measurements were made before and after systemic administration of the cyclooxygenase inhibitor ibuprofen and again after L-NMMA. L-NMMA reduced baseline FBF at rest (2.7 +/- 0.4 to 1.6 +/- 0.2 ml.100 ml-1.min-1; P < 0.05) and had a modest effect on peak forearm vascular conductance and flow (forearm vascular conductance = 31.1 +/- 3.1 vs. 25.7 +/- 2.5 ml.min-1.100 ml forearm-1.100 mmHg of perfusion pressure-1.min-1, P < 0.05; FBF = 26.6 +/- 2.9 vs. 22.8 +/- 2.6 ml.100 ml-1.min-1, P = 0.055). Total excess flow above baseline during reactive hyperemia was unaffected by L-NMMA (14.3 +/- 3.0 vs. 13.1 +/- 2.4 ml/100 ml; P < 0.05). Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 +/- 1.9 to 20.3 +/- 2.7 ml.100 ml-1.min-1 (P < 0.05), but had no effect on total excess flow above baseline, Infusion of L-NMMA after ibuprofen reduced FBF at rest by 40%, had no effect on peak flow, but reduced total excess flow above baseline from 12.0 +/- 2.5 to 7.6 +/- 1.3 ml/100 ml (P < 0.05). These date demonstrate that NO synthase inhibition has a modest effect on peak vasodilation during reactive hyperemia but plays a minimal role later. Prostaglandins appear to be important determinants of peak flow. The effects of NO synthase inhibition during reactive hyperemia may also be potentiated by concurrent cyclooxygenase inhibition.

Adolescent↗

Delay time adjustments to minimize errors in breath-by-breath measurement of Vo2 during exercise.

If the delay time between gas concentration and flow signals is not adequately corrected during breath-by-breath analysis of expired gas, an error in calculation of oxygen consumption (Vo2) will result. To examine the frequency and delay time dependences of errors in Vo2 measurement, six healthy men exercised at 100, 200, and 250 W on a cycle ergometer while breath-by-breath assessment of Vo2 was made simultaneously with collection of expired air. Subjects breathed first at normal rates (15-30 breaths/min) and then at 70 breaths/min. Each subject performed each level of exercise twice by using erroneous values for the delay time between gas concentration and flow signals. At normal breathing frequencies, errors in Vo2 measurement were +/- 10% over the full range of delay times used, and the errors were not tightly correlated with variations in delay times from optimum. However, at 70 breaths/min, errors approached +/- 30% as the variations in delay times deviated +/- 0.1 s from the optimal, and the errors were highly correlated with the variations in delay times. We conclude that there is greater potential for errors in Vo2 measurement with incorrect delay time at higher breathing frequencies. These findings suggest that the optimal delay time for breath-by-breath systems should be adjusted by using high breathing frequencies.

Adult↗

Role of nitric oxide in exercise hyperaemia during prolonged rhythmic handgripping in humans.

1. We sought to determine whether the vasodilating molecule nitric oxide (NO) contributes to the forearm hyperaemia observed during prolonged rhythmic handgripping in humans. 2. Two bouts of exercise were performed during experimental protocols conducted on separate days. During each protocol the subject performed a 10 min and a 20 min bout of rhythmic (30 min-1) handgripping at 15% of maximum. Two exercise bouts were required to facilitate pharmacological interventions during the second protocol. Blood flow in the exercising forearm was measured every minute with plethysmography during brief pauses in the contractions. During both exercise bouts in the first protocol, forearm blood flow increased 2- to 3-fold above rest after 1 min of handgripping and remained constant at that level throughout the exercise. 3. During the 10 min bout of exercise in the second protocol, acetylcholine was given via a brachial artery catheter at 16 micrograms min-1 for 3 min to evoke NO release from the vascular endothelium. This caused forearm blood flow to increase above the values observed during exercise alone. 4. During the 20 min trial of handgripping in the second protocol, the NO synthase blocker NG-monomethyl-L-arginine (L-NMMA) was infused in the exercising forearm via the brachial catheter after 5 min of handgripping. The L-NMMA was infused at 4 mg min-1 for 10 min. 5. L-NMMA during exercise caused forearm blood flow to fall to values approximately 20-30% lower than those observed during exercise alone. When ACh was given during exercise after L-NMMA administration the rise in blood flow was also blunted, indicating blockade of NO synthase. These data suggest NO plays a role in exercise hyperaemia in humans.

Acetylcholine↗

Oxidative capacity of human muscle fiber types: effects of age and training status.

Morphometry and oxidative capacity of slow-twitch (type I) and fast-twitch (type IIa and IIb) muscle fibers obtained from vastus lateralis needle biopsies were compared between younger (21-30 yr) and older (51-62 yr) normal fit (maximal O2 uptake = 47.0 vs. 32.3 ml.kg-1.min-1) and endurance-trained (66.3 vs. 52.7 ml.kg-1.min-1) men (n = 6/group). The older groups had smaller type IIa (31%) and IIb (40%) fiber areas and fewer capillaries surrounding these fibers than did younger groups. The reduced type II fiber areas and capillary contacts associated with aging were also observed in the older trained men. However, the capillary supply per unit type II fiber area was not affected by age but was enhanced by training. Additionally, on the basis of quantitative histochemical analysis, succinate dehydrogenase activities of type IIa fibers in the older trained men [4.07 +/- 0.68 (SD) mmol.min-1.l-1] were similar to those observed in younger trained men (4.00 +/- 0.48 mmol.min-1.l-1) and twofold higher than in older normal fit men (2.01 +/- 0.65 mmol.min-1.l-1; age x fitness interaction, P < 0.05). Type I muscle fibers were unaffected by age but were larger and had more capillary contacts and higher succinate dehydrogenase activities in the trained groups. The findings of this study suggest that aging results in a decrease in type II fiber size and oxidative capacity in healthy men and that this latter effect can be prevented by endurance training. Conclusions regarding the effects of age and training status on muscle capillarization depend largely on how these data are expressed.

Adult↗

Protein intake and athletic performance.

For most of the current century, exercise/nutritional scientists have generally accepted the belief that exercise has little effect on protein/amino acid requirements. However, during the same time period many athletes (especially strength athletes) have routinely consumed diets high in protein. In recent years, the results of a number of investigations involving both strength and endurance athletes indicate that, in fact, exercise does increase protein/amino acid need. For endurance athletes, regular exercise may increase protein need by 50 to 100%. For strength athletes, the data are less clear; however, protein intakes in excess of sedentary needs may enhance muscle development. Despite these observations increased protein intake may not improve athletic performance because many athletes routinely consume 150 to 200% of sedentary protein requirements. Assuming total energy intake is sufficient to cover the high expenditures caused by daily training, a diet containing 12 to 15% of its energy from protein should be adequate for both types of athletes.

Dietary Proteins↗