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Biomedical subjects

T E Graham

Publications and source records attributed to T E Graham.

At least 91 records · Page 5Linked to original sources

Estimation of the mitochondrial redox state in human skeletal muscle during exercise.

The mitochondrial redox (NAD+/NADH) state can be used as a reflection of oxygen availability within the mitochondrion. Previous studies using isolated muscle preparations suggest that active muscle is not hypoxic during lactate production, whereas experiments with humans come to the opposite conclusion. Six men exercised for 5 min at 75% maximal O2 consumption (VO2max) and then at 100% VO2max to exhaustion. Ammonia, oxoglutarate (alpha-ketoglutarate), and glutamate, as well as lactate, were measured in biopsies (vastus lateralis) taken at the end of each exercise. The three former metabolites were used to determine the mass action ratio of glutamate dehydrogenase and thus were used as an estimate of the mitochondrial redox state. Muscle lactate increased (P less than 0.05) to 14.5 and 24.5 mmol/kg wet wt after 75 and 100% VO2max, respectively. At both exercise intensities, muscle ammonia rose (P less than 0.05), glutamate fell (P less than 0.05) to only 30-35% of rest levels, and oxoglutarate declined (P less than 0.05). Despite the high levels of muscle lactate accumulation, the estimated mitochondrial redox rate rose 300% (P less than 0.05) in both exercise bouts. This response should increase the activity of key oxidative enzymes and promote increased VO2. Furthermore the data do not support the concept that muscle lactate is formed because of tissue hypoxia.

Adult↗

Thermal and metabolic responses to cold by men and by eumenorrheic and amenorrheic women.

Previous work has suggested that men (M) are more sensitive to cold stress than women. There have also been observations that suggest that amenorrheic women (AW) are less thermally responsive than eumenorrheic women (EW). We investigated the hypothesis that M, EW, and AW would have different responses to cold stress. The subjects (6/group) were tested four times: twice at rest for 60 min (5 and 22 degrees C) and twice in a progressive exercise test (5 and 22 degrees C). At rest at 22 degrees C AW had a lower O2 uptake (VO2) than M and lower rectal (Tre) and finger temperatures than EW. At rest at 5 degrees C both AW and EW had lower skin temperature (Tsk) than M, but there were no group differences in peripheral Tsk sites. M increased VO2 after 10 min and EW after 20 min of cold stress; however, AW did not increase metabolism until 60 min. In the two exercise tests Tre increased in proportion to relative work load; in the 5 degrees C test there was little evidence that exercise increased Tsk sites above rest levels. Few of the metabolic or thermal differences could be accounted for by body fatness, body surface area (BSA), or BSA/kg. The data support the hypothesis that M, EW, and AW have different responses to cold stress.

Adult↗

Thermal, metabolic, and cardiovascular changes in men and women during cold stress.

Our understanding of the responses of men and women to cold stress is extremely limited. Various scientists have suggested that there could be gender differences in thermoregulatory responses due to sexual dimorphism in body fatness and its distribution, in body surface area, and in mass. In addition, there are also several lines of evidence supporting the hypothesis that there are gender-specific physiological responses to body cooling. In cold water studies, women cool more rapidly than men when at rest; this potentially greater stimulus does not result in a greater metabolic response by the women. If both groups increase their metabolism by performing a prescribed amount of exercise, there are no differences in body cooling. However, if they exercise spontaneously, the women select a lower metabolic rate and experience greater body cooling. Thus, it appears that women are less thermally sensitive to cold water. In cold air stress women have a lower mean skin temperature than men, but this is not observed in peripheral skin sites. In contrast to cold water, women do not experience greater drops in deep body temperature than men in cold air. Furthermore, men may be more metabolically sensitive than women to cold air stress. Men also respond to cold air with a bradycardia and increased stroke volume, while women show no change in these parameters. Similarly, men show a greater blood pressure response than women to local cooling of a hand or the face. Many of these gender-specific responses cannot be explained fully by differences in body morphology and support the concept that men and women respond differently to the cold.

Adaptation, Physiological↗

Gender differences in cardiovascular and metabolic responses to cold and exercise.

This study was conducted because of the paucity of information concerning gender differences in the cardiovascular and metabolic responses to cold stress. Lightly clad men (n = 8) and women (n = 8) were tested in 21 and 5 degrees C environments during a 20-min rest, followed by 20 min each of 50, 100, and 150 W of exercise. At 21 degrees C there was no gender differences in VO2 or cardiac output. Cold lowered skin temperature more in women than in men, but women demonstrated no differences in heart rate, stroke volume, or VO2 at 5 and 21 degrees C. The women's noradrenaline levels in the cold were higher than comparable 21 degrees C data at rest and 50 W and increased with work intensity in both tests. In contrast, men had a lower heart rate, higher stroke volume, and higher VO2 throughout the 5 degrees C treatment compared with 21 degrees C. The men's noradrenaline response to 5 degrees C was similar to that of women at rest and 50 W, but the level subsequently declined at 100 and 150 W. Thus, the women do not show a heart rate-stroke volume shift in either resting or exercising states in cold environments. Furthermore, the data fail to support that either skin cooling or changes in noradrenaline cause the bradycardia and enhanced stroke volume seen in men.

Adult↗

Hyperoxia, mitochondrial redox state, and lactate metabolism of in situ canine muscle.

The effect of hyperoxia on lactate production and release and the mitochondrial NAD+-to-NADH ratio was studied in the in situ canine gastrocnemius to determine whether elevated PO2 altered metabolic regulation. Dogs breathed either air (21% O2) [arterial O2 partial pressure (PaO2) 90 mmHg; n = 8] or hyperoxia (100% O2) (PaO2 546 mmHg; n = 8). The left muscle was stimulated for 10 min at 3 Hz and then both right and left muscles were quick frozen in N2. Hyperoxia did not affect O2 uptake, blood flow, and developed tension. Activity increased glucose 6-phosphate (G-6-P), D-fructose 6-phosphate (F-6-P), NH3, lactate, and F-6-P/F-1,6-P in both treatment groups. No significant differences in arterial or venous lactate, muscle lactate, glucose uptake, or glycogen depletion were noted in hyperoxia. Cytoplasmic NAD+/NADH was in a more oxidized state in hyperoxia at rest but not during activity. The increase in NH3 with stimulation was significantly larger in hyperoxia. Activity decreased alpha-ketoglutarate in hyperoxia but not in air. At stimulation, the estimated mitochondrial NAD+/NADH increased in both groups suggesting that hypoxia was not present. Thus hyperoxia did not affect mitochondrial redox state or lactate production and release in active muscle.

Animals↗

Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women.

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.

Adult↗

Muscle and blood ammonia and lactate responses to prolonged exercise with hyperoxia.

Investigations using nonsteady-state and fatiguing exercise protocols have demonstrated a strong relationship between ammonia and lactate metabolism and have suggested a cause and effect relationship between these two variables. We investigated the lactate-ammonia response using prolonged exercise and inspiration of hyperoxic gas (60% O2-40% N2). The exercise consisted of either 70-75% maximal O2 uptake (VO2 max) for 40 min (series 1, n = 6) or 75-80% VO2max for 30 min (series 2, n = 6) with the subjects inspiring room air on one occasion and hyperoxia in the other test. In both series blood ammonia rose continuously throughout the exercise regardless of the inspired gas treatment; in contrast blood lactate did not increase after 10 min with room air, and with hyperoxia blood lactate was reduced. Muscle lactate and ammonia (series 2; vastus lateralis) had responses similar to the blood data. The data demonstrated no apparent lactate-ammonia relationship with prolonged exercise or in response to hyperoxia, suggesting that ammonia production can be independent of lactate metabolism. The data also suggest that type I fibers can be a major source of ammonia in humans.

Adult↗

Skeletal muscle lactate release and glycolytic intermediates during hypercapnia.

The effects of respiratory acidosis on glycolysis in the autoperfused canine gastrocnemius-plantaris were studied using anesthetized dogs that were ventilated either with air (n = 30) or with 4% CO2-21% O2-75% N2 (n = 30). The left muscle group was stimulated at 3 Hz for up to 20 min, after which the active and the contralateral resting muscles were removed and frozen in liquid N2. Blood flow, VO2, Vco2, and tension development were unaffected by CO2. Glycogen catabolism was not affected, but lactate release (La) was lower (P less than 0.05) during activity with CO2; and greater fructose 6-phosphate, fructose 6-phosphate/fructose 1,6-diphosphate, and alpha-glycerophosphate/dihydroxyacetone phosphate ratios resulted (P less than 0.05). With respiratory acidosis, muscle lactate tended to accumulate early in contractions, but a net lactate uptake occurred during the last 10 min of contractions. Thus, respiratory acidosis reduced lactate efflux and there was a net uptake late in the contraction period. Glycogen phosphorylase did not appear to be affected by the respiratory acidosis, but there was evidence of inhibition at the phosphofructokinase step as well as a tendency for lactate to accumulate within the muscle. La often occurred in a direction contrary to the muscle-venous lactate concentration difference with either air or CO2 and La also decreased far more rapidly over time than did the arterial-venous H+.

Acidosis, Respiratory↗

Effect of menstrual cycle phase and exercise training on serum lipids.

Studies of serum lipids in women training are inconclusive and have not considered menstrual hormones. Women (N = 8, 20-25 yrs) were studied over 3 consecutive cycles. The first cycle was a control cycle and then they trained for two cycles (3 times/wk for 30 min/day at 60% max HR reserve). Blood samples were drawn 5 to 7 days after the onset of menses (M) and mid-luteal (L) of all three cycles. Cycle phase (i.e. M vs L) did not influence total cholesterol or HDL cholesterol but triglyceride (TG) was higher (p less than 0.05) at M. The training period (65 +/- 7.5 days (SD) resulted in a significant (p less than 0.05) increase in VO2 max and decrease in resting HR. Training resulted in a decline (p less than 0.05) in HDL cholesterol from M1 to M2 (1.32 +/- 0.26 to 1.12 +/- 0.23 mmol/L) and a return to control by M3 (1.36 +/- 0.37 mmol/L). Training also resulted in TG declining (p less than 0.05) from L1 to L2 and from M2 to M3. Cycle phase only affected TG. Exercise training, however, resulted in a decline in TG and an initial decline in HDL cholesterol and a return to control levels during the second month of training.

Adult↗

Male-female responses in various body temperatures during and following exercise in cold air.

During cold exposure women have lower skin temperatures on the trunk and legs. This study evaluated whether these colder temperatures were also manifested in peripheral sites (nose, chin, and finger) where frost bite often occurs. In addition, the core temperature responses to passive rewarming were studied to evaluate whether women experience greater afterdrop as a result of colder shell temperatures. The subjects, eight males (M) and eight females (F), were tested on four occasions, once each at +10, +3.5, -3.5, and -10 degrees C. Each day the subject, clothed in sweat clothes and coveralls, performed 6 bouts of intermittent exercise (20 min. exercise (60W), 10 min. rest) for 3 h in the designated temperature and then rested in +21 degrees C for 1 h. The F had lower Tsk in every test, but finger, nose, and chin temperatures were never lower in F. There were no M-F differences in core temperature during cold exposure or during recovery, even though the Tsk would predict that F had a colder shell. Furthermore, there was no apparent relationship between Tsk rewarming and changes in T core. The data demonstrated no M-F differences in potential for either frost bite or for afterdrop in core temperature.

Adult↗

A comparison of 'anaerobic' components of O2 debt and the Wingate test.

This study compared measurements which were considered traditionally to reflect alactacid and lactacid components of anaerobic metabolism. Subjects (men (N = 9) and women (N = 5)) on one occasion performed an exhaustive cycle ergometer ride at VO2 max and had peak lactate and O2 debt (fast and slow components) determined. On a second occasion, they performed a Wingate test. All data were normalized for body weight. Very few correlations were found between O2 debt or peak lactate and the peak power, mean power and power decrease of the Wingate test. In particular, both peak lactate and the fast O2 debt component had low, nonsignificant correlations with either peak or mean power. The study failed to support the traditional assumptions that both tests are quantifying the same anaerobic energy systems.

Anaerobiosis↗

A longitudinal study of changes in aerobic fitness, body composition, and energy intake in primigravid patients.

Sixteen primigravid patients were studied on four occasions (once in each trimester and again at 4 weeks' post partum) for predicted VO2 max (Canadian Home Fitness Test), body weight, and percentage of body fat (skin folds) and caloric intake (3 day food diary). The VO2 max declined significantly from first to second to third trimester and rose post partum to the second-trimester level. Energy intake was constant but body weight and fat rose progressively until after birth. When subjects were divided into "fit" (n = 8) and "unfit" (n = 8) groups, the fit group had significantly greater VO2 max, lower heart rate and diastolic pressure, and less body fat. These differences were not present at third trimester but were present again in the postpartum data. There were no differences in delivery or neonatal data.

Adult↗

Effects of menstrual cycle on metabolic responses to exercise.

Selected substrate and hormonal responses to exercise were compared in two phases of the menstrual cycle. Exercise-induced changes in substrate [glucose, lactate, free fatty acids (FFA), glycerol] and hormonal patterns [luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin, progesterone (P), growth hormone (GH), cortisol] were compared in the follicular and luteal phases of the menstrual cycle in 24-h-fasted (n = 5), glucose-loaded (n = 6; 1.50 g/kg, 20% solution), and control subjects (n = 8). A treadmill walk was maintained for 60 min (30 min, 40% VO2 max; 30 min, 80% VO2 max). Blood samples were obtained 5 min before, 15, 30, 45, and 60 min during, and 30 min after exercise. In the glucose group a blood sample was also taken 20 min before exercise, and glucose was ingested 15 min before exercise. Within each nutritional group the metabolic and endocrine responses to exercise were similar in the two phases for glucose, lactate, glycerol, LH, FSH, and cortisol (P greater than 0.05). In the glucose group the FFA response was lower in the luteal phase (P less than 0.05). In the fasted subjects insulin and GH responses were elevated in the luteal phase (P less than 0.05). P responses in the control and glucose groups were markedly greater in the luteal phase (P less than 0.05). In the fasted subjects no alteration in P occurred in either phase (P less than 0.05), and the LH concentration was lower in these subjects relative to the control groups (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of hypercapnia and hyperoxia on metabolism during exercise.

It has been postulated that the respiratory acidosis associated with hyperoxia (HO) may mediate some of the metabolic effects that are traditionally attributed to the elevation in PaO2. Five subjects performed 30 min of steady-state exercise (65% VO2max) on eight occasions while inspiring either 21 or 60% O2 in combination with 0, 2, 4, or 6% CO2. Statistical significance was accepted if P less than 0.05. The four HO tests were associated with increased VO2 and lower R and blood lactate. However, when compared to the four normoxic tests, all of the hypercapnic (HC) conditions (independent of the inspired O2 percent) had statistically lower blood lactate. Hypercapnia was associated with lower R values and increased blood H+. Regression analysis demonstrated relationships between H+ and R, as well as between H+ and blood lactate. These findings are independent of whether 21 or 60% O2 was inspired, and support the hypothesis that acidosis, not PO2, mediates the effects related to HO.

Bicarbonates↗