The energy cost of locomotion on the level and on gradients for the red deer (Cervus elaphus).

The oxygen consumption (Vo2) of three castrated male red deer was measured while they walked on a treadmill at 7 degree and 14 degree slopes and on the level at speeds varying from 44.3 to 172.9 m.min(-1). The energy cost of horizontal locomotion in excess of standing was 2.6 J kg(-1).m(-1). The cost of maintenance of posture when walking was the same as that of standing. The energy cost of walking up gradients was 21.5 J kg(-1).vertical m(-1). These results are discussed in relation to values reported for other species.     

A feedback-controlled treadmill (treadmill-on-demand) and the spontaneous speed of walking and running in humans.

A novel apparatus, composed by a controllable treadmill, a computer, and an ultrasonic range finder, is here proposed to help investigation of many aspects of spontaneous locomotion. The acceleration or deceleration of the subject, detected by the sensor and processed by the computer, is used to accelerate or decelerate the treadmill in real time. The system has been used to assess, in eight subjects, the self-selected speed of walking and running, the maximum "reasonable" speed of walking, and the minimum reasonable speed of running at different gradients (from level up to +25%). This evidenced the speed range at which humans neither walk nor run, from 7.2 +/- 0.6 to 8.4 +/- 1.1 km/h for level locomotion, slightly narrowing at steeper slopes. These data confirm previous results, obtained indirectly from stride frequency recordings. The self-selected speed of walking decreases with increasing gradient (from 5.0 +/- 0.8 km/h at 0% to 3.0 +/- 0.9 km/h at +25%) and seems to be approximately 30% higher than the speed that minimizes the metabolic energy cost of walking, obtained from the literature, at all the investigated gradients. The advantages, limitations, and potential applications of the newly proposed methodology in physiology, biomechanics, and pathology of locomotion are discussed in this paper.     

Performance and metabolic responses to a high caffeine dose during prolonged exercise.

The present study examined whether a high caffeine dose improved running and cycling performance and altered substrate metabolism in well-trained runners. Seven trained competitive runners [maximal O2 uptake (VO2max) 72.6 +/- 1.5 ml.kg-1.min-1] completed four randomized and double-blind exercise trials at approximately 85% VO2max; two trials running to exhaustion and two trials cycling to exhaustion. Subjects ingested either placebo (PL, 9 mg/kg dextrose) or caffeine (CAF, 9 mg/kg) 1 h before exercise. Endurance times were increased (P less than 0.05) after CAF ingestion during running (PL 49.2 +/- 7.2 min, CAF 71.0 +/- 11.0 min) and cycling (PL 39.2 +/- 6.5 min, CAF 59.3 +/- 9.9 min). Plasma epinephrine concentration [EPI] was increased (P less than 0.05) with CAF before running (0.22 +/- 0.02 vs. 0.44 +/- 0.08 nM) and cycling (0.31 +/- 0.06 vs. 0.45 +/- 0.06 nM). CAF ingestion also increased [EPI] (P less than 0.05) during exercise; PL and CAF values at 15 min were 1.23 +/- 0.13 and 2.51 +/- 0.33 nM for running and 1.24 +/- 0.24 and 2.53 +/- 0.32 nM for cycling. Similar results were obtained at exhaustion. Plasma norepinephrine was unaffected by CAF at rest and during exercise. CAF ingestion also had no effect on respiratory exchange ratio or plasma free fatty acid data at rest or during exercise. Plasma glycerol was elevated (P less than 0.05) by CAF before exercise and at 15 min and exhaustion during running but only at exhaustion during cycling. Urinary [CAF] increased to 8.7 +/- 1.2 and 10.0 +/- 0.8 micrograms/ml after the running and cycling trials.(ABSTRACT TRUNCATED AT 250 WORDS)     

The energy cost of running increases with the distance covered

The net energy cost of running per unit of body mass and distance (Cr, ml O2.kg-1.km-1) was determined on ten amateur runners before and immediately after running 15, 32 or 42 km on an indoor track at a constant speed. The Cr was determined on a treadmill at the same speed and each run was performed twice. The average value of Cr, as determined before the runs, amounted to 174.9 ml O2.kg-1.km-1, SD 13.7. After 15 km, Cr was not significantly different, whereas it had increased significantly after 32 or 42 km, the increase ranging from 0.20 to 0.31 ml O2.kg-1.km-1 per km of distance (D). However, Cr before the runs decreased, albeit at a progressively smaller rate, with the number of trials (N), indicating an habituation effect (H) to treadmill running. The effects of D alone were determined assuming that Cr increased linearly with D, whereas H decreased exponentially with increasing N, i.e. Cr = Cr0 + a D + He-bN. The Cr0, the "true" energy cost of running in nonfatigued subjects accustomed to treadmill running, was assumed to be equal to the average value of Cr before the run for N equal to or greater than 7 (171.1 ml O2.kg-1.km-1, SD 12.7; n = 30).(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in spring-mass model parameters and energy cost during track running to exhaustion

The purpose of this study was to determine whether exhaustion modifies the stiffness characteristics, as defined in the spring-mass model, during track running. We also investigated whether stiffer runners are also the most economical. Nine well-trained runners performed an exhaustive exercise over 2000 meters on an indoor track. This exhaustive exercise was preceded by a warm-up and was followed by an active recovery. Throughout all the exercises, the energy cost of running (Cr) was measured. Vertical and leg stiffness was measured with a force plate (Kvert and Kleg, respectively) integrated into the track. The results show that Cr increases significantly after the 2000-meter run (0.192 +/- 0.006 to 0.217 +/- 0.013 mL x kg(-1) x m(-1)). However, Kvert and Kleg remained constant (32.52 +/- 6.42 to 32.59 +/- 5.48 and 11.12 +/- 2.76 to 11.14 +/- 2.48 kN.m, respectively). An inverse correlation was observed between Cr and Kleg, but only during the 2000-meter exercise (r = -0.67; P < or = 0.05). During the warm-up or the recovery, Cr and Kleg, were not correlated (r = 0.354; P = 0.82 and r = 0.21; P = 0.59, respectively). On track, exhaustion induced by a 2000-meter run has no effect on Kleg or Kvert. The inverse correlation was only observed between Cr and Kleg during the 2000-meter run and not before or after the exercise, suggesting that the stiffness of the runner may be not associated with the Cr.     

Energetics of locomotion in African pygmies

The energy cost of walking (Cw) and running (Cr), and the maximal O2 consumption (VO2max) were determined in a field study on 17 Pygmies (age 24 years, SD 6; height 160 cm, SD 5; body mass 57.2 kg, SD 4.8) living in the region of Bipindi, Cameroon. The Cw varied from 112 ml.kg-1.km-1, SD 25 [velocity (v), 4 km.h-1] to 143 ml.kg-1.km-1, SD 16 (v, 7 km.h-1). Optimal walking v was 5 km.h-1. The Cr was 156 ml.kg-1.km-1, SD 14 (v, 10 km.h-1) and was constant in the 8-11 km.h-1 speed range. The VO2max was 33.7 ml.kg-1.min-1, i.e. lower than in other African populations of the same age. The Cr and Cw were lower than in taller Caucasian endurance runners. These findings, which challenge the theory of physical similarity as applied to animal locomotion, may depend either on the mechanics of locomotion which in Pygmies may be different from that observed in Caucasians, or on a greater mechanical efficiency in Pygmies than in Caucasians. The low Cr values observed enable Pygmies to reach higher running speeds than would be expected on the basis of their VO2max.     

Effect of hypercapnia and hypoxia on respiratory muscle activation in humans

We studied the electromyographic activity of the diaphragm (EMGdi) and abdominal external oblique (EMGeo) muscles in response to progressive hypercapnia (HCVR) and hypoxia (HVR) in five normal males. The slopes of the regression lines relating log EMGdi activity to minute volume of ventilation (VE) were steeper during HVR runs than HCVR runs (mean +/- SE, 0.03201 +/- 0.00724 vs. 0.02729 +/- 0.00676, P less than 0.03). Phasic expiratory EMGeo activity was seen in 15 of 15 HCVR runs but in only 6 of 15 HVR runs. Furthermore, the maximum level of VE attained before the onset of EMGeo activity was significantly lower during HCVR runs than during HVR runs (23.1 +/- 2.5 vs. 34.8 +/- 4.01/min, P less than 0.003). We conclude that in awake humans 1) the diaphragm is activated to a greater extent by hypoxia than hypercapnia at a given VE and 2) hypercapnia causes a more consistent recruitment of abdominal expiratory activity at lower VE than does hypoxia.     

Serum and urine chromium as indices of chromium status in tannery workers

Serum and urinary Cr levels of a selected group of men exposed to CrIII in four Southern Ontario tanneries were compared with those of men not exposed to Cr. Fasted blood samples were obtained from 72 tannery workers (TW; mean age +/- SD = 36 +/- 12 years) and from 52 controls (CS; mean age +/- SD = 41 +/- 13 years). Serum Cr levels as determined by graphite furnace atomic absorption spectrophotometry were significantly higher (P = 0.0001) for TW (median 0.49 ng/ml, range 0.37-0.81) than for CS (median 0.15 ng/ml, range 0.12-0.20). Urine samples were collected from 49 TW and 43 CS on a Friday pm and from 42 TW on a Monday am. Urinary creatine (Cre) was determined by the Jaffe reaction. For Friday samples, the median urinary Cr/Cre ratio was significantly higher (P = 0.0001) for TW (median 0.83 ng/mg, range 0.48-1.82) than for CS (median 0.18 ng/mg, range 0.13-0.26). For TW, Cr/Cre was correlated with serum Cr (r = 0.72, P = 0.0001). Neither urinary Cr/Cre nor serum Cr was correlated with length of employment in the tanning industry. There were significant differences in serum Cr levels and urinary Cr/Cre ratios among TW employed in different areas of the tanneries. For TW, the median urinary Cr/Cre ratio for Monday morning samples was significantly lower than for Friday afternoon samples (P = 0.03). These data indicate that CrIII is absorbed and that serum and urine Cr in tannery workers may be indices of Cr exposure and status.     

Whole body protein kinetics in women: effect of pregnancy and IDDM during anabolic stimulation

The effects of pregnancy and type 1 diabetes [insulin-dependent diabetes mellitus (IDDM)] on protein metabolism are still uncertain. Therefore, six normal and five IDDM women were studied during and after pregnancy, using [(13)C]leucine and [(2)H(5)]phenylalanine with a hyperinsulinemic-euglycemic clamp and amino acid infusion. Fasting total plasma amino acids were lower in pregnancy in normal but not IDDM women (2,631 +/- 427 vs. 2,057 +/- 471 and 2,523 +/- 430 vs. 2,500 +/- 440 micromol/l, respectively). Whole body protein breakdown (leucine) increased in pregnancy [change in normal (delta N) and IDDM women (delta D) 0.59 +/- 0.40 and 0.48 +/- 0.26 g. kg(-1). day(-1), both P < 0.001], whereas reductions in protein breakdown due to insulin/amino acids (delta N -0.57 +/- 0.19, delta D -0.58 +/- 0.20 g. kg(-1). day(-1), both P < 0.001) were unaffected by pregnancy. Protein breakdown in IDDM women was not higher than normal, and neither pregnancy nor type 1 diabetes altered the insulin sensitivity of amino acid turnover. Nonoxidized leucine disposal (protein synthesis) increased in pregnancy (delta N 0.67 +/- 0.45, delta D 0.64 +/- 0.34 g. kg(-1). day(-1), both P < 0.001). Pregnancy reduced the response of phenylalanine hydroxylation to insulin/amino acids in both groups (delta N -1.14 +/- 0.74, delta D -1. 12 +/- 0.77 g. kg(-1). day(-1), both P < 0.05). These alterations may enable amino acid conservation for protein synthesis and accretion in late pregnancy. Well-controlled type 1 diabetes caused no abnormalities in the regulation of basal or stimulated protein metabolism.     

Endurance training induces muscle-specific changes in mitochondrial function in skinned muscle fibers.

The present study was conducted to investigate the potential role of changes in the apparent K(m) for ADP and in the functional coupling of the creatine (Cr) kinase (CK) system (CK efficiency) in explaining the tighter integration of ATP supply and demand after exercise training. Mitochondrial function was assessed in saponin-skinned fibers from the soleus and the deep red portion of the medial gastrocnemius isolated from trained (T; treadmill running, 5 days/wk, 4 wk) and control (C) female Sprague-Dawley rats. In the soleus, V(max) in the presence of 1 mM ADP was increased by 21% after training (5.9 +/- 0.2 vs. 4.7 +/- 0.4 nmol O(2). min(-1). mg dry wt(-1), P < 0.05). This was accompanied by no change in the K(m) for ADP measured in the absence of Cr (146 +/- 9 vs. 149 +/- 13 microM in T and C, respectively) and in its presence (50 +/- 4 vs. 48 +/- 6 microM in T and C, respectively) and in CK efficiency [K(m) (+Cr)/K(m) (-Cr)]. In contrast, in the red gastrocnemius, training decreased, by 35%, the apparent K(m) for ADP in the absence (83 +/- 5 vs. 129 +/- 9 microM, P < 0.01) of Cr, without affecting V(max) (6.2 +/- 0.4 vs. 6.7 +/- 0.3 nmol O(2). min(-1). mg dry wt(-1) in T and C, respectively) and CK efficiency. These results thus suggest that training induces muscle-specific adaptations of mitochondrial function and that a change in the intrinsic sensitivity of mitochondria to ADP could at least partly explain the tighter integration of ATP and demand commonly observed after training.     

Increased energy intake minimizes weight loss in men at high altitude.

The hypothesis that high-altitude weight loss can be prevented by increasing energy intake to meet energy requirement was tested in seven men, 23.7 +/- 4.3 (SD) yr, taken to 4,300 m for 21 days. Energy intake required to maintain body weight at sea level was found to be 3,118 +/- 300 kcal/day, as confirmed by nitrogen balance. Basal metabolic rate (BMR), determined by indirect calorimetry, increased 27% on day 2 at altitude and then decreased and reached a plateau at 17% above the sea level BMR by day 10. Energy expended during strenuous activities was 37% lower at altitude than at sea level. Fecal excretion of energy, nitrogen, total fiber, and total volatile fatty acids was not significantly affected by altitude. Energy intake at altitude was adjusted after 1 wk, on the basis of the increased BMR, to 3,452 +/- 452 kcal/day. Mean nitrogen balance at altitude was negative (-0.25 +/- 0.71 g/day) before energy intake was adjusted but rose significantly thereafter (0.20 +/- 0.71 and 0.44 +/- 0.66 g/day during weeks 2 and 3). Mean body weight decreased 2.1 +/- 1.0 kg over the 3 wk of the study, but the rate of weight loss was significantly diminished after the increase in energy intake (201 +/- 75 vs. 72 +/- 48 g/day). Individual regression lines drawn through 7-day segments of body weight showed that in four of seven subjects the slopes of body weight were not significantly different from zero after the 2nd wk. Thus weight loss ceased in four of seven men in whom increased BMR at altitude was compensated with increased energy intake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treadmill economy in girls and women matched for height and weight.

We investigated differences in walking (80 m/min) and running (147 m/min) economy [submaximal oxygen consumption (VO(2) (submax))] between adolescent girls (n = 13; age = 13.3 +/- 0.9 yr) and young women (n = 23; age = 21.0 +/- 1.5 yr). Subjects were matched for height (158.7 +/- 2.9 cm) and weight (52.1 +/- 3.0 kg). Anthropometric measures (height, weight, breadths, skinfolds) and preexercise oxygen consumption were obtained on all subjects before submaximal and maximal treadmill exercise. Anthropometric measures were similar between groups, as was maximal oxygen consumption (girls, 47.7 +/- 5.2; women, 47.5 +/- 5.7 ml. kg(-1). min(-1)). VO(2) (submax) was significantly greater (P < 0.0002) in girls compared with women during both walking (16.4 +/- 1.7 vs. 14.4 +/- 1. 1 ml. kg(-1). min(-1)) and running (38.1 +/- 3.7 vs. 33.9 +/- 2.4 ml. kg(-1). min(-1)). Preexercise oxygen consumption (4.4 vs. 3.9 ml. kg(-1). min(-1)) accounted for only a fraction of the differences found in exercise economy. Although heart rate and respiratory frequency were greater in the girls in both walking (118 +/- 11 vs. 104 +/- 12 beats/min and 31 +/- 3 vs. 25 +/- 4 breaths/min, respectively; P < 0.002) and running (180 +/- 15 vs. 163 +/- 17 beats/min and 47 +/- 11 vs. 38 +/- 8 breaths/min; P < 0.005), this did not likely account for a large part of the difference in VO(2) (submax) between groups.     

A protocol of intermittent exercise (shuttle runs) to train young basketball players

The purpose of this study was to set up a protocol of intermittent exercise to train young basketball players. Twenty-one players were asked to complete (a) an incremental test to determine maximal oxygen uptake (VO2max), the speed at the ventilatory threshold (vthr) and the energy cost of "linear" running (Cr) and (b) an intermittent test composed of 10 shuttle runs of 10-second duration and 30-seconds of recovery (total duration: about 6 minutes). The exercise intensity (the running speed, vi) was set at 130% of vthr. During the intermittent tests, oxygen uptake (VO2) and blood lactate concentration (Lab) were measured. The average pretraining VO2 calculated for a single bout (131 ± 9 ml · min(-1) kg(-1)) was about 2.4 times greater than the subjects' measured VO2max (54.7 ± 4.6 ml · min(-1) · kg(-1)). The net energy cost of running (9.2 ± 0.9 J · m(-1) · kg(-1)) was about 2.4 times higher than that measured at constant "linear" speed (3.9 ± 0.3 J · m(-1) · kg(-1)). The intermittent test was repeated after 7 weeks of training: 9 subjects (control group [CG]) maintained their traditional training schedule, whereas for 12 subjects (experimental group [EG]) part of the training was replaced by intermittent exercise (the same shuttle test as described above). After training, the VO2 measured during the intermittent test was significantly reduced (p < 0.05) in both groups (-10.9% in EG and - 4.6 in CG %), whereas Lab decreased significantly only for EG (-31.5%). These data suggest that this training protocol is effective in reducing lactate accumulation in young basketball players.     

Effects of load and gradient on energy cost of running

This study quantified the interaction of electromyography (EMG) obtained from the vastus lateralis and metabolic energy cost of running (C(r); mL·[mass+load](-1)·meter(-1)), an index of running economy, during submaximal treadmill running. Experiments were conducted with and without load on the back on a motor-driven treadmill on the downhill, level and uphill slopes. The obtained EMG was full-wave rectified and integrated (iEMG). The iEMG was divided into eccentric (ECC) and concentric (CON) phases with a foot sensor and a knee-joint goniometer. The ratio of ECC to CON (ECC/CON ratio) was regarded as the muscle elastic capacity during running on each slope. The C(r) was determined as the ratio of the 2-min steady-state VO(2) to the running speed. We found a significant decrease in the C(r) when carrying the load at all slopes. The ECC/CON ratio was significantly higher in the load condition at the downhill and level slopes, but not at the uphill slope. A significant gradient difference was observed in the C(r) (downuphill). Thus, an alteration of Cr by the gradient and load was almost consistent with that of the ECC/CON ratio. The ECC/CON ratio, but not the rotative torque (T) functioning around the center of body mass, significantly correlated with C(r) (r=-0.41, p<0.05). These results indicated that the ECC/CON ratio, rather than T, contributed to one of the energy-saving mechanisms during running with load.     

Effects of ion transport inhibitors on MCh-mediated secretion from porcine airway submucosal glands.

Submucosal glands secrete macromolecules and liquid that are essential for normal airway function. To determine the mechanisms responsible for airway gland secretion and the interaction between gland secretion and epithelial ion transport, studies were performed in porcine tracheal epithelia by using the hillocks and Ussing techniques. No significant baseline gland fluid flux (J(G)) was measured by the hillocks technique after 3 min, and the epithelia had an average potential difference of 7.5 +/- 0.5 mV (lumen negative) with a short-circuit current of 73 +/- 4 microA/cm(2), as measured by the Ussing technique. The secretagogue methacholine induced concentration-dependent increases in J(G) after 3 min from 0.003 microl. min(-1). cm(-2) at 0.1 microM to 0.41 +/- 0.04 microl. min(-1). cm(-2) at 1,000 microM, with a 0.9 +/- 0.1 mV hyperpolarization of the epithelium at 1,000 microM. When the epithelium was pretreated for 3 min with the sodium channel blocker amiloride, the methacholine (1,000 microM)-induced J(G) increased to 0.67 +/- 0.09 microl. min(-1). cm(-2), and the hyperpolarization increased to 2.2 +/- 0.5 mV over the amiloride-pretreated level. When pretreated for 3 min with the chloride channel blocker diphenylamine-2-carboxylic acid, the methacholine (1,000 microM)-induced J(G) was inhibited to 0.20 +/- 0.06 microl. min(-1). cm(-2), and the methacholine-induced hyperpolarization was abolished. These data indicate that, in porcine airways, methacholine-induced J(G) may be increased by inhibition of sodium absorption and decreased by inhibition of chloride secretion.     

Effects of hyperosmotic medium on hepatocyte volume, transmembrane potential and intracellular K+ activity

Hepatocyte transmembrane potential (Vm) behaves as an osmometer and varies with changes in extracellular osmotic pressure created by altering the NaCl concentration in the external medium (Howard, L.D. and Wondergem, R. (1987) J. Membr. Biol. 100, 53). We now have demonstrated similar effects on Vm by increasing external osmolality with added sucrose and not altering ionic strength. We also have demonstrated that hyperosmotic stress-induced depolarization of Vm results from changes in membrane K+ conductance, gK, rather than from changes in the K+ equilibrium potential. Vm and aKi of hepatocytes in liver slices were measured by conventional and ion-sensitive microelectrodes, respectively. Cell water vols. were estimated by differences in wet and dry weights of liver slices after 10-min incubations. Effect of hyperosmotic medium on membrane transference number for K+, tK, was measured by effects on Vm of step-changes in external [K+]. Hepatocyte Vm decreased 34, 52 and 54% when tissue was superfused with medium made hyperosmotic with added sucrose (50, 100 and 150 mM). Correspondingly, aKi increased 10, 18 and 29% with this hyperosmotic stress of added sucrose. Tissue water of 2.92 +/- 0.10 kg H2O/kg dry weight in control solution decreased to 2.60 +/- 0.05, 2.25 +/- 0.06 and 2.22 +/- 0.05 kg H2O/kg dry weight with additions to medium of 50, 100 and 150 mM sucrose, respectively. Adding 50 mM sucrose to medium decreased tK from 0.20 +/- 0.01 to 0.05 +/- 0.01. Depolarization by 50% with hyperosmotic stress (100 mM sucrose) also occurred in Cl-free medium where Cl- was substituted with gluconate. We conclude that hepatocytes shrink during hyperosmotic stress, and the aKi increases. The accompanying decrease in Vm is opposite to that expected by an increase in aKi, and at least in part results from a concomitant decrease in gK. Changes in membrane Cl- conductance most likely do not contribute to osmotic stress-induced depolarization, since equivalent decreases in Vm occurred with added sucrose in cells depleted of Cl- by superfusing tissue with Cl-free medium.     

Cardiorespiratory and lactate responses to a 1-hour submaximal running at the lactate threshold

Cardiorespiratory and blood lactate (La) responses to prolonged submaximal running at an intensity relative to lactate threshold (LT) were examined in 15 recreational runners, aged 19 to 32. In test 1 where treadmill speed was progressively incremented by 10-20m/min until exhaustion, oxygen uptake at the LT (VO2 @ LT: 2.34 +/- 0.331/min or 41.6 +/- 5.7 ml/kg/min) and VO2max (3.58 +/- 0.341/min or 63.6 +/- 5.5 ml/kg/min) were measured. In test 2, the subject was required to run on the treadmill for 1 hour at a fixed velocity (Vt) which corresponded to his Vt @ LT. As expected, mean VO2 ranged during the 1-h submaximal running from 2.31 +/- 0.411/min or 63.0 +/- 7.8% VO2max at min 10-20 to 2.52 +/- 0.351/min or 69.2 +/- 6.2% VO2max at min 50-60, both of which were close to VO2 @ LT (65.2 +/- 4.4% VO2max). The slight decrease in blood La was found from min 20 to min 60, and this was accompanied by a parallel decline in respiratory exchange ratio. Shifts in the energy substrate toward a reliance on fat oxidation may occur during the course of 1-h running at Vt @t LT. The small oxygen debt observed after the 1-h running may confirm the assumption that prolonged running at Vt at LT would be performed in an almost fully aerobic steady state. We conclude that prolonged running at Vt @ LT may possibly maximize health-related benefits in the healthy adult.     

Effect of a recombinant human growth hormone preparation on the urinary 15nitrogen balance in growth-hormone-deficient children

In 10 patients with idiopathic growth hormone (GH) deficiency (9 boys and 1 girl, aged 7.5-14.5 years, mean 12.1 +/- 2.2 years), urinary 15N-balance studies were performed before and on recombinant hGH (2 x 3 IU/m2 of body surface area subcutaneously on consecutive days). Before and on the 2nd day of recombinant hGH, 99% 15N-labeled ammonium chloride (0.05 g/kg, divided in 3 doses per day, corresponding to 389 +/- 30 mg/m2 of 15N) was administered and 24 h urine was collected. In urine, total nitrogen and the percentage of 15N were measured. From the ingested and excreted quantity, a urinary 15N balance was calculated. Mean 15N percentage from total N was 3.3 +/- 0.5. In 9 patients, basal 15N balance was +79 +/- 15 mg/m2 or +2.9 +/- 0.4 mg/kg. On recombinant hGH, it was +166 +/- 16 mg/m2 or +6.1 +/- 0.6 mg/kg (p less than 0.001). The recombinant hGH-induced positive 15N balance change was +87 +/- 17 mg/m2 or +3.2 +/- 0.6 mg/kg. 1 patient with a higher basal 15N balance (+196 mg/m2, +7.1 mg/kg) had no positive 15N balance change due to latent hypothalamic hypothyroidism. In previous similar studies with pituitary hGH the change of 15N balance was +80 +/- 27 mg/m2 or +2.8 +/- 1.1 mg/kg. It is concluded that the acute nitrogen-retaining effect of recombinant hGH is at least equal to that of pituitary hGH.     

Epinephrine infusion enhances muscle glycogenolysis during prolonged electrical stimulation

To determine the effects of epinephrine (EPI) infusion on muscle glycogenolysis and force production, the quadriceps muscles of both legs in six subjects were intermittently stimulated for 30 min. Contractions lasted 1.6 s (20 Hz) and were separated by 1.6 s of rest. EPI was infused (approximately 0.14 micrograms.kg body wt-1.min-1) in one leg during the last 15 min and the vastus lateralis was biopsied at rest (control leg only) and after 15, 18 (EPI leg only), and 30 min of stimulation. EPI infusion doubled the mole fraction of phosphorylase a (22.5 +/- 4.1 to 44.8 +/- 9.0%) and glycogenolysis (2.16 +/- 0.72 to 5.45 +/- 0.81 mmol glucosyl U.kg dry muscle wt-1.min-1) during stimulation. Muscle glucose 6-phosphate increased from 3.04 +/- 0.17 to 6.43 +/- 0.20 mmol/kg dry muscle wt, and lactate increased from 25.8 +/- 4.4 to 34.3 +/- 4.6 mmol/kg after 3 min of EPI infusion. Isometric force production was unaltered by EPI infusion. These results demonstrate a strong glycogenolytic effect of EPI infusion during prolonged electrical stimulation and suggest that the extra pyruvate formed was converted mainly to lactate. Exclusive anaerobic metabolism of the extra substrate would provide only a 10% increase in total ATP production, possibly accounting for the lack of improvement in force production. We suggest that the decrease in force production during prolonged electrical stimulation is related to decreased excitation of the contractile mechanism rather than inhibition of cross-bridge turnover caused by a shortage of energy or accumulation of hyproducts.     

Metabolic and vascular support for the role of myoglobin in humans: a multiparametric NMR study

In human muscle the role of myoglobin (Mb) and its relationship to factors such as muscle perfusion and metabolic capacity are not well understood. We utilized nuclear magnetic resonance (NMR) to simultaneously study the Mb concentration ([Mb]), perfusion, and metabolic characteristics in calf muscles of athletes trained long term for either sprint or endurance running after plantar flexion exercise and cuff ischemia. The acquisitions for (1)H assessment of Mb desaturation and concentration, arterial spin labeling measurement of muscle perfusion, and (31)P spectroscopy to monitor high-energy phosphate metabolites were interleaved in a 4-T magnet. The endurance-trained runners had a significantly elevated [Mb] (0.28 +/- 0.06 vs. 0.20 +/- 0.03 mmol/kg). The time constant of creatine rephosphorylation (tauPCr), an indicator of oxidative capacity, was both shorter in the endurance-trained group (34 +/- 6 vs. 64 +/- 20 s) and negatively correlated with [Mb] across all subjects (r = 0.58). The time to reach maximal perfusion after cuff release was also both shorter in the endurance-trained group (306 +/- 74 vs. 560 +/- 240 s) and negatively correlated with [Mb] (r = 0.56). Finally, Mb reoxygenation rate tended to be higher in the endurance-trained group and was positively correlated with tauPCr (r = 0.75). In summary, these NMR data reveal that [Mb] is increased in human muscle with a high oxidative capacity and a highly responsive vasculature, and the rate at which Mb resaturates is well correlated with the rephosphorylation rate of Cr, each of which support a teleological role for Mb in O(2) transport within highly oxidative human skeletal muscle.