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Biomedical subjects

G E Butterfield

Publications and source records attributed to G E Butterfield.

49 records · Page 3Linked to original sources

Muscle accounts for glucose disposal but not blood lactate appearance during exercise after acclimatization to 4,300 m.

We hypothesized that the increased blood glucose disappearance (Rd) observed during exercise and after acclimatization to high altitude (4,300 m) could be attributed to net glucose uptake (G) by the legs and that the increased arterial lactate concentration and rate of appearance (Ra) on arrival at altitude and subsequent decrease with acclimatization were caused by changes in net muscle lactate release (L). To evaluate these hypotheses, seven healthy males [23 +/- 2 (SE) yr, 72.2 +/- 1.6 kg], on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-D2]glucose (Brooks et al., J. Appl. Physiol. 70: 919-927, 1991) and [3-13C]lactate (Brooks et al., J. Appl. Physiol. 71:333-341, 1991) and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 uptake (65 +/- 2% of both acute altitude and acclimatization peak O2 uptake). Glucose and lactate arteriovenous differences across the legs and arms and leg blood flow were measured. Leg G increased during exercise compared with rest, at altitude compared with sea level, and after acclimatization. Leg G accounted for 27-36% of Rd at rest and essentially all glucose Rd during exercise. A shunting of the blood glucose flux to active muscle during exercise at altitude is indicated. With acute altitude exposure, at 5 min of exercise L was elevated compared with sea level or after acclimatization, but from 15 to 45 min of exercise the pattern and magnitude of L from the legs varied and followed neither the pattern nor the magnitude of responses in arterial lactate concentration or Ra. Leg L accounted for 6-65% of lactate Ra at rest and 17-63% during exercise, but the percent Ra from L was not affected by altitude. Tracer-measured lactate extraction by legs accounted for 10-25% of lactate Rd at rest and 31-83% during exercise. Arms released lactate under all conditions except during exercise with acute exposure to high altitude, when the arms consumed lactate. Both active and inactive muscle beds demonstrated simultaneous lactate extraction and release. We conclude that active skeletal muscle is the predominant site of glucose disposal during exercise and at high altitude but not the sole source of blood lactate during exercise at sea level or high altitude.

Acclimatization↗

Altitude acclimatization and energy metabolic adaptations in skeletal muscle during exercise.

To determine whether the working muscle is able to sustain ATP homeostasis during a hypoxic insult and the mechanisms associated with energy metabolic adaptations during the acclimatization process, seven male subjects [23 +/- 2 (SE) yr, 72.2 +/- 1.6 kg] were given a prolonged exercise challenge (45 min) at sea level (SL), within 4 h after ascent to an altitude of 4,300 m (acute hypoxia, AH), and after 3 wk of sustained residence at 4,300 m (chronic hypoxia, CH). The prolonged cycle test conducted at the same absolute intensity and representing 51 +/- 1% of SL maximal aerobic power (VO2 max) and between 64 +/- 2 (AH) and 66 +/- 1% (CH) at altitude was performed without a reduction in ATP concentration in the working vastus lateralis regardless of condition. Compared with rest, exercise performed during AH resulted in a greater increase (P < 0.05) in muscle lactate concentration (5.11 +/- 0.68 to 22.3 +/- 6.1 mmol/kg dry wt) than exercise performed either at SL (5.88 +/- 0.85 to 11.5 +/- 3.1) or CH (5.99 +/- 0.88 to 12.4 +/- 2.1). These differences in lactate concentration have been shown to reflect differences in arterial lactate concentration and glycolysis (Brooks et al. J. Appl. Physiol. 71: 333-341, 1991). The reduction in glycolysis at least between AH and CH appears to be accompanied by a tighter metabolic control. During CH, free ADP was lower and the ATP-to-free ADP ratio was increased (P < 0.05) compared with AH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

The generation and characterization of silicon carbide whiskers (fibers) for inhalation toxicology studies.

Atmospheres of silicon carbide whiskers (wh) were required for a repeated dose lung deposition study and a subchronic inhalation toxicity study, each involving exposure to three concentrations of whiskers for 6 hr/day, 5 days/week for 1 or 13 weeks. Target concentrations were 0, 500, 1500, and 7500 wh/cc. By using the mean fiber length (10 microns), diameter (0.555 micron), and density (3.2 g/cc) of the bulk material, target mass concentrations were approximately 0, 4, 12, and 60 mg/m3. The Pitt III generator, developed for cotton fiber dispersion at the University of Pittsburgh, was selected. This instrument consists of a vertical 18-in. long cylinder, which is closed at each end with rubber dams and coupled at the base to a loudspeaker. The sonic energy from the loudspeaker fluidizes the test material and the whiskers in the air column are carried out with the exhaust air. The output of the Pitt III generator was altered by changing the sound energy input, the rate of introduction of the test material into the fluidizing cylinder, or the airflow through the cylinder. Separate generation systems were used for each inhalation chamber. Chamber atmospheres were characterized gravimetrically and samples were analyzed by scanning electron microscopy. Mean mass and number concentrations for the subchronic study were 0.09, 3.93, 10.7, and 60.5 mg/m3 and 0, 630, 1746, and 7276 wh/cc, respectively. Weighted mean values for whisker diameters, lengths, and aspect ratios were 0.560 micron, 4.53 microns, and 8.62, respectively. Although whisker lengths were less than half those of the bulk material, nearly 30% of the whiskers were greater than 5 microns long.

Administration, Inhalation↗

Nutritional intake in patients with senile dementia of the Alzheimer type.

The dietary intake of 29 healthy controls was compared with that of 35 community-dwelling patients with probable or definite senile dementia of the Alzheimer type (SDAT), based on NINCDS-ADRDA criteria. The control subject or the caregiver of the SDAT patient completed a 3-day estimated-dietary-intake record. Foods offered to patients were chosen, for the most part, by caregivers, but SDAT patients were allowed to eat ad libitum from those choices, and food consumed was recorded. Dietary intake was evaluated against the 1989 Recommended Dietary Allowances (RDA). Dietary intakes did not differ significantly between control and SDAT patients for any of the 32 nutrients analyzed. The controls and SDAT patients met the RDA guidelines for intake of total energy, protein, and micronutrients, with the exception of female SDAT patients, who did not consume a minimum of two thirds of the RDA for vitamin D. All biochemical indices of nutritional status were within normal limits for the SDAT patients. In addition, cognitive function did not correlate with intake of any nutrient studied. We conclude that moderately impaired, community-dwelling patients with SDAT do not differ from healthy controls in nutritional status or nutrient intake. Neither general nor nutrient-specific malnutrition was present in this population. Based on this cross-sectional study, malnutrition does not appear to be a major contributor to the pathogenesis of Alzheimer disease. However, this investigation examined only a single point in time, when patients were being fed by caregivers, so that the role of malnutrition at the beginning of the disease was not addressed.

Aged↗

Arterial catecholamine responses during exercise with acute and chronic high-altitude exposure.

Exercise at high altitude is a stress that activates the sympathoadrenal systems, which could affect responses to acute altitude exposure and promote adaptations during chronic altitude exposure. However, catecholamine levels are not clearly described over time at high altitude. In seven male volunteers (23 yr, 72 kg), resting arterial norepinephrine concentrations (ng/ml) on arrival at Pikes Peak (0.338 +/- 0.041) decreased compared with sea-level values (0.525 +/- 0.034) but increased to above sea-level values after 21 days at 4,300 m (0.798 +/- 0.052). Furthermore, during 45 min of constant submaximal exercise, values were similar at sea level (1.670 +/- 0.221) and on acute exposure to 4,300 m (2.123 +/- 0.086) but increased after 21 days of chronic exposure (2.693 +/- 0.216). By contrast, resting arterial epinephrine values (ng/ml) during acute and chronic exposure (0.708 +/- 0.033 vs. 0.448 +/- 0.026) both exceeded those of sea level (0.356 +/- 0.020). During exercise values on arrival were greater than at sea level (0.921 +/- 0.024 vs. 0.397 +/- 0.035) but fell to 0.612 +/- 0.025 ng/ml after 21 days. Exercise norepinephrine levels were related to systemic vascular resistance measurements (r = 0.93), whereas epinephrine levels were related to circulating lactate (r = 0.95). We conclude that during exercise at altitude there is a dissociation between norepinephrine, an indicator of sympathetic neural activity, and epinephrine, an indicator of adrenal medullary response. These actions may account for different metabolic and physiological responses to acute vs. chronic altitude exposure.

Adult↗

Increased dependence on blood glucose after acclimatization to 4,300 m.

To evaluate the hypothesis that altitude exposure and acclimatization result in increased dependency on blood glucose as a fuel, seven healthy males (23 +/- 2 yr, 72.2 +/- 1.6 kg, mean +/- SE) on a controlled diet were studied in the postabsorptive condition at sea level (SL), on acute altitude exposure to 4,300 m (AA), and after 3 wk of chronic altitude exposure to 4,300 m (CA). Subjects received a primed continuous infusion of [6,6-2D]glucose and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the SL maximal O2 consumption (VO2 max; 65 +/- 2% of altitude VO2 max). At SL, resting arterial glucose concentration was 82.4 +/- 3.2 mg/dl and rose significantly to 91.2 +/- 3.2 mg/dl during exercise. Resting glucose appearance rate (Ra) was 1.79 +/- 0.02 mg.kg-1.min-1; this increased significantly during exercise at SL to 3.71 +/- 0.08 mg.kg-1.min-1. On AA, resting arterial glucose concentration (85.8 +/- 4.1 mg/dl) was not different from sea level, but Ra (2.11 +/- 0.14 mg.kg-1.min-1) rose significantly. During exercise on AA, glucose concentration rose to levels seen at SL (91.4 +/- 3.0 mg/dl), but Ra increased more than at SL (to 4.85 +/- 0.15 mg.kg-1.min-1; P less than 0.05). Resting arterial glucose was significantly depressed with CA (70.8 +/- 3.8 mg/dl), but resting Ra increased to 3.59 +/- 0.08 mg.kg-1.min-1, significantly exceeding SL and AA values.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

Oxygen transport during steady-state submaximal exercise in chronic hypoxia.

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

Decreased reliance on lactate during exercise after acclimatization to 4,300 m.

We hypothesized that the increased exercise arterial lactate concentration on arrival at high altitude and the subsequent decrease with acclimatization were caused by changes in blood lactate flux. Seven healthy men [age 23 +/- 2 (SE) yr, wt 72.2 +/- 1.6 kg] on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-2D]glucose (Brooks et al. J. Appl. Physiol. 70:919-927, 1991) and [3-13C]lactate and rested for a minimum of 90 min followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 consumption (VO2peak; 65 +/- 2% of both acute altitude and acclimatization). During rest at sea level, lactate appearance rate (Ra) was 0.52 +/- 0.03 mg.kg-1.min-1; this increased sixfold during exercise to 3.24 +/- 0.19 mg.kg-1.min-1. On acute exposure, resting lactate Ra rose from sea level values to 2.2 +/- 0.2 mg.kg-1.min-1. During exercise on acute exposure, lactate Ra rose to 18.6 +/- 2.9 mg.kg-1.min-1. Resting lactate Ra after acclimatization (1.77 +/- 0.25 mg.kg-1.min-1) was intermediate between sea level and acute exposure values. During exercise after acclimatization, lactate Ra (9.2 +/- 0.7 mg.kg-1.min-1) rose from resting values but was intermediate between sea level and acute exposure values. The increased exercise arterial lactate concentration response on arrival at high altitude and subsequent decrease with acclimatization are due to changes in blood lactate appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Discrepancies between energy intake and expenditure in physically active women.

Energy intake and expenditure in women runners and non-runners were assessed by weighed food records, evaluation of minute-by-minute activity diaries, and indirect calorimetry. All participants were adapted to their stated activity levels for at least 6 months and maintained a constant body-weight throughout their participation. Calculated daily energy intake equalled calculated expenditure in non-runners (7300 (SD 1536) v. 7476 (SD 872) kJ/d), but calculated energy expenditure in women running about 54 km/week was found to exceed intake by more than 2700 kJ/d (8259 (SD 1466) v. 10963 (SD 1367), P less than 0.01). The runners showed no evidence of compensating for the increased energy expenditure associated with running by engaging in lower-intensity activities during non-running time. Further, runners did not decrease energy expended at various activities. The findings suggest that women adapted to high levels of activity may possess mechanisms to maintain body-weight without significantly increasing energy intake.

Activities of Daily Living↗

Whole-body protein utilization in humans.

Recently, several authors have recommended protein intakes as high as 2 to 3 g X kg body weight-1 X d-1 for physically active individuals. Review of the literature cited to support this recommendation, as well as other published and unpublished work, suggests that there are at least three variables which have not been sufficiently controlled or investigated in much of the research done, making such a recommendation premature. These variables are timing of sampling relative to initiation of an exercise program (training), energy and protein intake associated with activity, and intensity of exercise performed. Several investigators report a 12- to 14-d adaptation period following initiation of an activity program during which nitrogen (N) balance falls and then returns near to equilibrium. Data collected during this adaptation period can be expected to reflect a more negative N balance than data collected after that time. Butterfield and co-workers have found that exercise at 40 to 50% of maximal oxygen consumption actually promotes N retention in previously untrained men given sufficient time to adjust to the new exercise regimen, allowing maintenance of N equilibrium on a marginal protein intake. Energy intake, energy balance, and quantity of protein ingested inter-act in this effect. Finally, recent experiments suggest that, at high intensity activities, energy balance becomes even more critical in the utilization of protein: when energy balance is negative, an intake of protein as high as 2 g X kg body weight-1 X d-1 may be inadequate to maintain N equilibrium in previously trained individuals exercising at 64% of maximal oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Proteins↗

Vitamin B6 utilization in active and inactive young men.

Two groups (22-37 yr) were studied to investigate the use of vitamin B6 with exercise. Four trained men (T) were confined and studied after they ran 10 and 5 miles/day, for two 4-wk periods. They were compared with six free-living inactive men (S) consuming the same diet that provided 4.2 mg of vitamin B6 each day. N-acetyl-L-methionine, was given (60 mg/kg) as a Vitamin B6 challenge on day 28 of each period, and 24-h urinary 4-pyridoxic acid (4-PA) and methionine metabolites were determined before and after the challenge. Basal 4-PA excretion was significantly lower (p less than or equal to 0.05) in T than in S. In T, postmethionine 4-PA was greater than basal, while in S, postmethionine 4-PA was lower. Compared with prechallenge, postchallenge metabolites decreased in T and increased in S. Basal 4-PA excretion provides no conclusive evidence of increased need for vitamin B6 in athletes: the postload excretion suggests that exercise may promote storage of the vitamin that is available for redistribution with increased need.

Adult↗

Physical activity improves protein utilization in young men.

Protein utilization in young men under circumstances of one or two periods of work and both adequate and surfeit energy intake was determined by nitrogen balance; protein intake was constant at the FAO/WHO (1973) safe level (0.57 g/kg body-weight). Physical activity affected protein utilization negatively by increasing sweat and faecal N losses, and positively by supporting increased energy intake. Efficiency with which surfeit energy improved N utilization (mg N retained/added kJ) was greater under circumstances of increased activity. Changes in body composition as determined by total body potassium and hydrostatic weighing supported the N retention values.

Adult↗

Nitrogen balance in men with adequate and deficient energy intake at three levels of work.

Two studies were conducted to investigate the effects of mild exercise on nitrogen balance in men given diets supplying adequate or slightly limiting energy. In experiment A the diet supplied 91 mg N/kg body weight (0.57 g protein/kg, the FAO/WHO safe level of intake) as egg white; in experiment B the same source was used to provide the 1980 NRC-RDA for adult males, 128 mg N/kg body weight (0.8 g protein/kg). By adjusting energy intake and activity, periods of energy equilibrium and negative energy balance (-15%) were achieved at three levels of activity (X for exercise): no programmed work (0.85X), 1 hour of treadmill walking (1.0X) and 1 hour each of treadmill and cycle ergometry (1.15X). "True" nitrogen balance (TNbal) was more positive or less negative during periods of energy equilibrium as compared to those of energy deficit. This effect of energy balance on TNbal increased with physical activity. At the lower protein intake the mean difference in TNbal between the period of energy equilibrium and that of energy deficit at 1.0X was 0.19 g N/day (nonsignificant difference) and 0.54 g N/day at 1.15X. When protein intake was increased, the difference in TNbal between periods of equilibrium and deficit was significant at all levels of activity: 0.65 g N/day at 0.85X, 0.93 g N/day at 1.0X and 1.09 g N/day at 1.15X. Physical activity was anabolic when energy balance was maintained. In experiment A the addition of 1 hour of exercise (1.0X to 1.15X) spared 2.5 mg N/kg body weight; reducing activity by 1 hour (1.0X to 0.85X) cost 1.4 mg N/kg body weight. In experiment B, TNbal was more positive with increased activity (by 5.9 mg N/kg body weight) and more negative (by 11.5 mg N/kg body weight) when the men were sedentary. During periods of energy deficit, the anabolic effect of activity was also present, although less markedly. When activity increased from 1 to 2 hours in experiment A, TNbal improved by 2.1 mg N/kg body weight and in experiment B, by 3.5 mg N/kg body weight. Thus, circumstances of negative energy balance with adequate protein intake are better tolerated when the energy deficit is generated by physical activity than when it derives from reduced intake; the picture when protein intake is marginal requires further investigation.

Adult↗