Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate

Roberts, A. C., G. E. Butterfield, A. Cymerman, J. T. Reeves, E. E. Wolfel, and G. A. Brooks. Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate. J. Appl. Physiol. 81(4): 1762-1771, 1996.We testedthe hypothesis that exposure to altitude decreases reliance on freefatty acids (FFA) as substrates and increases dependency on bloodglucose. Therefore, the effects of exercise, hypobaric hypoxia, andaltitude acclimatization on FFA, glycerol and net glucose uptake andrelease [ = 2(leg blood flow)(arteriovenous concentration)]and on fatty acid (FA) consumption by the legs (= 3 × glycerolrelease + FFA uptake) were measured. Because sympathetic responses havebeen implicated, we utilized nonspecific -blockade and observedresponses to exercise, altitude, and altitude acclimatization. Westudied six healthy -blocked men () and five matched controls (C)during rest and cycle ergometry exercise (88 W) at 49% of sea-level(SL) peak O₂ uptake at the sameabsolute power output on acute altitude exposure (A1; barometric pressure = 430 Torr) and after 3 wk of chronic altitude exposure to4,300 m (A2). During exercise at SL, FA consumption rates increased (P < 0.05). On arrival at 4,300 m,resting leg FFA uptake and FA consumption rates were not significantlydifferent from those at SL. However, after acclimatization to altitude,at rest leg FA consumption decreased to essentially zero in both C and groups. During exercise at altitude after acclimatization, leg FAconsumption increased significantly, but values were less than at SL orA1 (P < 0.05), whereas glucoseuptake increased relative to SL values. Furthermore, -blockadesignificantly increased glucose uptake relative to control. We concludethat 1) chronic altitude exposure decreases leg FA consumption during rest and exercise;2) relative to SL, FFA uptakedecreases while glucose uptake increases during exercise at altitude;and 3) -blockade potentiatesthese effects.

     

Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis

Rates of fatty acid oxidation increase rapidly in both rat heart and skeletal muscle in the early postnatal period. Therefore, we examined in heart and soleus muscle, (a) whether there were rapid changes in fatty acid transporter (FAT/CD36, FABPpm) mRNA and protein expression early in life (days 10 –36) and thereafter (days 84, 160, 365), and (b) whether the rates of fatty acid transport and the plasmalemmal content of FAT/CD36 and FABPpm were altered. Protein expression was altered rapidly from day 10–36 in both heart (FAT/CD36 only, +21%, P < 0.05)) and soleus muscle (FAT/CD36 + 100%, P < 0.05; FABPpm −20%, P < 0.05), with no further changes thereafter (P < 0.05). Rates of fatty acid transport (day 10 vs day 160) were increased in heart (+33%, P < 0.05) and muscle (+85%, P < 0.05), and were associated with concomitant increases in plasmalemmal FABPpm (+44%, P < 0.05) and FAT/CD36 (+16%, P < 0.05) in the heart, and only plasmalemmal FAT/CD36 in muscle (+90%, P < 0.05). Therefore, known changes in the rates of fatty acid oxidation in heart and muscle early in life appear to be accompanied by a concurrent upregulation in the rates of fatty acid transport and the expression of FAT/CD36 in heart and muscle, as well as an increase in plasmalemmal FAT/CD36 and FABPpm in the heart, and only plasmalemmal FAT/CD36 in soleus muscle. We speculate that the rapid upregulation of fatty acid transport rates in heart and muscle are needed to support the increased rates of fatty oxidation that have been previously observed in these tissues.     

Decreased level of 2,3-diphosphoglycerate and alteration of structural integrity in erythrocytes infected with Plasmodium falciparum in vitro

2,3-Diphosphoglycerate (2,3-DPG), an intracellular metabolite of glycolytic pathway is known to affect the oxygen binding capacity of haemoglobin and mechanical properties of the red blood cells. 2,3-DPG levels have been reported to be elevated during anaemic conditions including visceral leishmaniasis. 2,3-DPG activity in P. falciparum infected red blood cells, particularly in cells infected with different stages of the parasite and its relationship with structural integrity of the cells is not known. Chloroquine sensitive and resistant strains of P. falciparum were cultured in vitro and synchronized cultures of ring, trophozoite and schizont stage rich cells along with the uninfected control erythrocytes were assayed for 2,3-DPG activity and osmotic fragility. It was observed that in both the strains, in infected erythrocytes the 2,3-DPG activity gradually decreased and osmotic fragility gradually increased as the parasite matured from ring to schizont stage. The decrease in 2,3-DPG may probably be due to increased pyruvate kinase activity of parasite origin, which has been shown in erythrocytes infected with several species of Plasmodium. The absence of compensatory increase in 2,3-DPG in P. falciparum infected erythrocytes may aggravate hypoxia due to anaemia in malaria and probably may contribute to hypoxia in cerebral malaria. As 2,3-DPG was not found to be increased in erythrocytes parasitized with P. falciparum, the increased osmotic fragility observed in these cells is not due to increased 2,3-DPG as has been suggested in visceral leishmaniasis.     

Effects of water restriction on growth performance,feed nutrient digestibility,carcass and meat traits of rabbits

The study investigates the effects of a post-weaning water restriction on performance, nutrient digestibility, carcass traits and meat quality of 84-day-old rabbits. A total of 1388 weaned rabbits (35 days) were randomly divided into two groups on the basis of BW and sex. The two groups were fed the same diets ad libitum both in the post-weaning (35 to 60 days) and fattening (61 to 84 days) periods. In the post-weaning period, one group (AL) also received drinking water ad libitum, whereas the other (WR) had a water restriction from 35 to 41 days 2 h/day; from 42 to 48 days 2.5 h/day; from 49 to 55 days 3 h/day; and from 56 to 60 days 4 h/day. During the fattening period, both groups had water-free access. Individual live weights and feed intake per cage were recorded weekly for 32 cages randomly chosen per group (64 rabbits) to calculate the BW gain, feed intake and feed conversion ratio (FCR). The apparent digestibility values of nutrients were measured using acid-insoluble ash. Carcass data were collected from 16 rabbits (8 males and 8 females) per group selected for similar final BW in both groups. Mortality from 35 to 60 days was higher in the AL group (10.1% v. 5.2%, for AL and WR, respectively, P < 0.0001). BW gain was higher for the AL group during both the post-weaning (+22.4%, P < 0.01) and the entire period (+7.5%, P < 0.05). Water restriction reduced feed intake both in the post-weaning (−17.4%, P < 0.0001) and in the entire period (−9.9%, P < 0.05). During the fattening period, FCR was lower for the WR group (5.15 v. 5.75 g/g, for WR and AL, respectively, P < 0.05). The apparent digestibilities of dry matter, organic matter, NDF, ADF and cellulose were greater in the restricted rabbits (+4.7%, +4.5%, +10.2%, +18.8% and +12.8%, P < 0.01, P < 0.01, P < 0.05, P < 0.01, P < 0.05, respectively). Perirenal and scapular fat percentages were higher in the AL rabbits (+30.7% and +116.6%, P < 0.01 and P < 0.001, respectively). Water restriction increased saturated fatty acids (C16:0, +12.9%, P < 0.05), lauroleic acid (C12:1, +75.0%, P < 0.01), n-3 polyunsaturated fatty acids (C20:5, +50.0%, P < 0.01 and C22:5, +16.6%, P < 0.05) and the n-3/n-6 ratio (+28.6%, P < 0.05). The applied water restriction between 35 and 60 days executed during the winter months improved the digestive health of rabbits, with no negative effects on carcass traits, or physical and chemical meat characteristics. However, from the animal welfare point of view, a water restriction can be criticized as a method to restrict feed intake.     

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500 m (barometric pressure 432 mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min · day⁻¹), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (V˙O_{2 max}) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P < 0.05) in the control group after intermittent exposure to hypoxia. In contrast, there was no significant increase in HVR in the training group after exposure. The HCVR in both groups was not changed by intermittent exposure to hypoxia, while V˙O_{2 max} increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans. Accepted: 18 March 1998     

Implications of moderate altitude training for sea-level endurance in elite distance runners

Elite distance runners participated in one of two studies designed to investigate the effects of moderate altitude training (inspiratory partial pressure of oxygen ≈115–125 mmHg) on submaximal, maximal and supramaximal exercise performance following return to sea-level. Study 1 (New Mexico, USA) involved 14 subjects who were assigned to a 4-week altitude training camp (1500–2000 m) whilst 9 performance-matched subjects continued with an identical training programme at sea-level (CON). Ten EXP subjects who trained at 1640 m and 19 CON subjects also participated in study 2 (Krugersdorp, South Africa). Selected metabolic and cardiorespiratory parameters were determined with the subjects at rest and during exercise 21 days prior to (PRE) and 10 and 20 days following their return to sea-level (POST). Whole blood lactate decreased by 23% (P < 0.05 vs PRE) during submaximal exercise in the EXP group only after 20 days at sea-level (study 1). However, the lactate threshold and other measures of running economy remained unchanged. Similarly, supramaximal performance during a standardised track session did not change. Study 2 demonstrated that hypoxia per se did not alter performance. In contrast, in the EXP group supramaximal running velocity decreased by 2% (P < 0.05) after 20 days at sea-level. Both studies were characterised by a 50% increase in the frequency of upper respiratory and gastrointestinal tract infections during the altitude sojourns, and two male subjects were diagnosed with infectious mononucleosis following their return to sea-level (study 1). Group mean plasma glutamine concentrations at rest decreased by 19% or 143 (74) μM (P < 0.001) after 3 weeks at altitude, which may have been implicated in the increased incidence of infectious illness. Accepted: 19 March 1998     

Unchanged in vivo P50 at high altitude despite decreased erythrocyte age and elevated 2,3-diphosphoglycerate

We measured hematological and erythrocyte O2 transport parameters in whole blood and density-separated erythrocytes in 11 mountaineers before and during 5 days of exposure to high altitude (4,559 m). We determined the in vivo (arterial pHblood and PCO2) and standard (pHblood = 7.4, PCO2 = 40 Torr) O2 tension at 50% O2 saturation of hemoglobin and (P50,vv and P50,st) and Bohr coefficients (BC) for fixed acid (H+) and CO2 and examined the contribution of the altered average age of circulating erythrocytes due to the stimulation of erythropoiesis on whole blood 2,3-diphosphoglycerate (2,3-DPG) and P50,st. At altitude, whole blood P50,vv remained almost unchanged, whereas P50,st and 2,3-DPG increased significantly (+4 Torr; 3.5 mumol/g hemoglobin). BCCO2 was elevated significantly at altitude. Serum erythropoietin increased transiently fourfold, iron utilization increased, and serum iron decreased by 66%. Reticulocyte counts increased, but other hematological parameters were unchanged. In density-separated erythrocytes, P50,st and 2,3-DPG increased with decreasing cell density but were higher in fractions with comparable reticulocyte counts in cells prepared at altitude than in those from control studies. Our data show that, despite the increase in 2,3-DPG and the decrease in average erythrocyte age, the in vivo hemoglobin-O2 affinity remains unchanged. P50,st values reflect the elevation of 2,3-DPG, and approximately 50% of the increase in both parameters can be ascribed to the increase in the number of reticulocytes and young erythrocytes.     

Sodium citrate ingestion and muscle performance in acute hypobaric hypoxia

Eight subjects were studied on four occasions following ingestion of a 300-ml solution containing either sodium citrate (C, 0.4g · kg^–1 body mass) or placebo (P, sodium chloride 0.045 g · kg^–1 body mass), at local barometric pressure (N, P _B approximately 740 mmHg, 98.7 kPa) or hypobaric hypoxia (HH, P _B = 463 mmHg, 61.7 kPa). At 2 h after ingestion of the solution, the subjects performed prolonged isometric knee-extension at 35% of the maximal voluntary contraction (MVC) measured either in N or HH. Results showed that ingestion of C led to an improvement in muscle endurance (P < 0.01). However, this increase in endurance time for knee extensor muscles was only significant in N ( +22%, P < 0.05, compared to + 15%, NS, at N and HH, respectively). Following ingestion of sodium citrate, pre-exercise bicarbonate concentrations and pH levels were significantly higher than those measured after P ingestion. A significant treatment effect was observed for blood lactate concentrations with values higher for C than for P after 4, 6 and 10 min of recovery (P < 0.05). Electromyographic signals (EMG) were obtained from the vastus lateralis muscle during the prolonged isometric contraction at 35% MVC. The mean power frequency (MPF) significantly decreased in time under both N-P and N-C conditions. In HH, no significant decrease in MPF was observed with time. The results suggest that C ingestion was an ergogenic aid enhancing endurance during a sustained isometric contraction. In addition, it is suggested that fatigue during prolonged isometric contraction in HH was not directly related to factors determining the EMG signs of fatigue.     

Thermoregulatory responses of paraplegic and able-bodied athletes at rest and during prolonged upper body exercise and passive recovery

The thermoregulatory responses of ten paraplegic (PA; T3/4-L4) and nine able-bodied (AB) upper body trained athletes were examined at rest and during prolonged arm-cranking exercise and passive recovery. Exercise was performed for 90 min at 80% peak heart rate, and at 21.5 (1.7)°C and 47.0 (7.8)% relative humidity on a Monark cycle ergometer (Ergomedic 814E) adapted for arm exercise. Mean peak oxygen uptake values for the PA and AB athlete groups were 2.12 (0.41) min⁻¹ and 3.19 (0.38) l · min⁻¹, respectively (P<0.05). At rest, there was no difference in aural temperature between groups [36.2 (0.4)°C for both groups]. However, upper body skin temperatures for the PA athletes were approximately 1.0 °C warmer than for the AB athletes, whereas lower body skin temperatures were cooler than those for the AB athletes (1.3 °C and 2.7 °C for the thigh and calf, respectively). Upper and lower body skin temperatures for the AB athletes were similar. During exercise, blood lactate peaked after 15 min of exercise for both groups [3.33 (1.26) mmol · l⁻¹ and 4.30 (1.03) mmol · l⁻¹ for the PA and AB athletes, respectively, P<0.05] and decreased throughout the remainder of the exercise period. Aural temperature increased by 0.7 (0.5)°C and 0.6 (0.4)°C for the AB and PA athletes, respectively. Calf skin temperature for the PA athletes increased during exercise by 1.4 (2.8)°C (P<0.05), whereas a decrease of 0.8 (2.0)°C (P<0.05) was observed for the AB athletes. During the first 20 min of recovery from exercise, the calf skin temperature of the AB athletes decreased further [−2.6 (1.3)°C; P<0.05]. Weight losses and changes in plasma volume were similar for both groups [0.7 (0.5) kg and 0.7 (0.4) kg; 5.4 (4.9)% and 9.7 (6.2)% for the PA and AB athletes, respectively]. In conclusion, the results of this study suggest that the PA athletes exhibit different thermoregulatory responses at rest and during exercise and passive recovery to those of upper body trained AB athletes. Despite this, during 90 min of arm-crank exercise in a cool environment, the PA athletes appeared to be at no greater thermal risk than the AB athletes. Accepted: 7 May 1997     

Acute hormone responses to heavy resistance lower and upper extremity exercise in young versus old men

Acute hormone responses of growth hormone (GH), total and free testosterone (TT and FT) and cortisol (C) to heavy resistance isometric exercise were examined in ten young men [YM 26.5 (SD 4.8) years] and ten old men [OM 70.0 (SD 3.7) years]. Loading conditions of the same relative intensity were created for the lower and upper extremity actions separately as well as for both of them together – lower extremity exercise (LE; knee extension), upper extremity exercise (UE; bench press extension), and lower and upper extremity exercise (LUE) performed simultaneously in a seated position. Single voluntary maximal isometric actions lasting for 5 s were performed repeatedly for ten repetitions (with a recovery of 5 s) for a total of four sets. The recovery time between the sets was 1 min. Each exercise led to large acute decreases in maximal isometric force in both YM (P < 0.001) and OM (P < 0.001) ranging from 41% to 26% with no significant differences between the groups. Serum GH concentrations increased in both YM (P < 0.05–0.01) and OM (P < 0.05) but the postexercise value in YM during LE was greater (P < 0.05) than for OM. The TT increased (P < 0.01–0.001) in YM in all three exercises, while in OM the increase occurred only during LE (P < 0.01). The exercises led to increases in FT in YM (P < 0.05 for LE and LUE), while in OM the increase occurred only during LUE (P < 0.05). The pre and postexercise FT were greater in YM (P < 0.001) than in OM. No significant changes occurred in C either in YM or in OM. The blood lactate concentrations increased during the exercises in both YM (P < 0.001) and OM (P < 0.05–0.001) but the postexercise values during LE and LUE in YM were greater (P < 0.05) than in OM. The present data would indicate that the responses of GH, TT and FT to heavy resistance isometric exercise are lowered with increasing age. The reduced acute hormone response together with the lowered basal values in FT in the older men compared to the young men may indicate decreased anabolic effects on muscles and may explain in part the loss of muscle mass and strength associated with aging. Accepted: 18 August 1997     

Mechanism of Activation of Caspase-9 and Caspase-3 during Hypoxia in the Cerebral Cortex of Newborn Piglets: The Role of Nuclear Ca<Superscript>2+</Superscript>-Influx

In previous studies, we have shown that cerebral hypoxia results in increased activity of caspase-9, the initiator caspase, and caspase-3, the executioner of programmed cell death. We have also shown that cerebral hypoxia results in high affinity Ca²⁺–ATPase-dependent increase in nuclear Ca²⁺-influx in the cerebral cortex of newborn piglets. The present study tests the hypothesis that inhibiting nuclear Ca²⁺-influx by pretreatment with clonidine, an inhibitor of high affinity Ca²⁺–ATPase, will prevent the hypoxia-induced increase in caspase-9 and caspase-3 activity in the cerebral cortex of newborn piglets. Thirteen newborn piglets were divided into three groups, normoxic (Nx, n = 4), hypoxic (Hx, n = 4), and hypoxic treated with clonidine (100 mg/kg) (Hx–Cl, n = 5). Anesthetized, ventilated animals were exposed to an FiO₂ of 0.21 (Nx) or 0.07 (Hx) for 60 min. Cerebral tissue hypoxia was documented biochemically by determining levels of ATP and phosphocreatine (PCr). Caspase-9 and -3 activity were determined spectrofluoro-metrically using specific fluorogenic synthetic substrates. ATP (μmoles/g brain) was 4.6 ± 0.3 in Nx, 1.7±0.4 in Hx (P < 0.05 vs. Nx), and 1.5 ± 0.2 in Hx–Cl (P < 0.05 vs. Nx). PCr (μmoles/g brain) was 3.6 ± 0.4 in Nx, 1.1 ± 0.3 in Hx (P < 0.05 vs. Nx), and 1.0 ± 0.2 in Hx–Cl (P < 0.05 vs. Nx). Caspase-9 activity (nmoles/mg protein/h) was 0.548 ± 0.0642 in Nx and increased to 0.808 ± 0.080 (P < 0.05 vs. Nx and Hx–Cl) in the Hx and 0.562 ± 0.050 in the Hx–Cl group (p = NS vs. Nx). Caspase-3 activity (nmoles/mg protein/h) was 22.0 ± 1.3 in Nx and 32 ± 6.3 in Hx (P < 0.05 vs. Nx) and 18.8 ± 3.2 in the Hx–Cl group (P < 0.05 vs. Hx). The data demonstrate that clonidine administration prior to hypoxia prevents the hypoxia-induced increase in the activity of caspase-9 and caspase-3. We conclude that the high afinity Ca²⁺–ATPase-dependent increased nuclear Ca²⁺ during hypoxia results in increased caspase-9 and caspase-3 activity.     

The effects of weight loss on relative bone mineral density in premenopausal women

Objective:

This study compared BMD relative to body weight following a ～6‐month weight loss program and a 1‐year weight maintenance phase in premenopausal women and determined whether African American (AA) and European‐American (EA) women's BMD respond similarly during weight loss.

Design and Methods:

Premenopausal women (n = 115, 34 ± 5 years) were evaluated in an overweight state (BMI between 27 and 30 kg/m²), following an 800 kcal/day diet/exercise program designed to reduce BMI<25 kg/m², and 1‐year following weight loss.

Results:

BMD relative to body weight (Z‐scores) increased after weight loss, but decreased during the 1‐year weight maintenance phase. All 1‐year follow‐up BMD Z‐scores were increased (except L1) compared to baseline measurements (P < 0.05). These sites included the hip neck (+0.088, P = 0.014), total hip (+0.099, P = 0.001), L2 (+0.127, P = 0.013), L3 (+0.135, P = 0.014), and L4 (+0.199, P = 0.002). AAs had significantly higher absolute BMD at all sites (P < 0.05) compared to EAs, but no time by race interactions were evident during weight loss (except in L3).

Conclusion:

These results may indicate that weight loss is safe with regard to bone health for overweight premenopausal women.     

Effect of temperature on hemolymph lactate and glucose concentrations in spiny lobster Panulirus interruptus during progressive hypoxia

Some metabolic fuels in hemolymph samples from the sinuses at the base of the third walking leg (pre-branchial blood) and from the cardiac sinus (post-branchial blood) in the red lobster, Panulirus interruptus, were evaluated during normoxia, hypoxia, and at the critical oxygen point (P_cr) at two temperatures of acclimatization. Three-way ANOVA indicated a significant effect of oxygen saturation R(6140)=19.84 in metabolic fuel concentrations. Lactate varied from 0.01 to 0.29 mg/ml at 20 °C, from 0.02 to 0.29 mg/ml at 27 °C, and increased significantly during hypoxia (P<0.05). Glucose varied from 0.10 to 0.27 mg/ml at 20 °C, from 0.13 to 0.33 mg/ml at 27 °C, and increased with temperature. Proteins varied from 80.78 to 119.99 mg/ml at 20 °C and from 82.99 to 130.30 mg/ml at 27 °C.     

ALPHA-CHAIN HEMOGLOBIN POLYMORPHISMS ARE CORRELATED WITH ALTITUDE IN THE DEER MOUSE,PEROMYSCUS MANICULATUS

In deer mouse (Peromyscus maniculatus) populations in the western United States, alpha-globin haplotype frequency, beta-globin haplotype frequency, and base-line blood oxygen affinity (measured after acclimation to low altitude) show strong correlations with native altitude. The correlations improve when an average regional altitude is substituted for the local altitude at collection sites. This substitution roughly compensates for the effects of gene exchange between populations in areas of highly variable topography. When subspecific effects are removed with covariate analyses a significant (P < 0.05) relationship remains only for alpha-globin haplotype frequency and altitude. Thus, alpha-globin haplotype frequency, beta-globin haplotype frequency, and base-line blood oxygen affinity may be explained by either subspecific or altitudinal effects, but subspecific effects explain a larger proportion of the variance. Part of the subspecific effect may be attributable to an underlying relationship of subspecies with altitude. The analyses for the alpha-globins in conjunction with other data on the effects of alpha-globins on blood oxygen affinity and whole-animal physiological performance are consistent with the hypothesis that the frequency of the alpha-globins evolved in response to selection resulting from the stress of high-altitude hypoxia.     

Vitamin C Pretreatment Attenuates Hypoxia-Induced Disturbance of Sodium Currents in Guinea Pig Ventricular Myocytes

As an important in vivo antioxidant, vitamin C is commonly used clinically to alleviate hypoxia-induced heart symptoms. To approach the protective mechanisms of vitamin C on hearts during hypoxia, we investigated the electrophysiological effects of vitamin C (1 mM, pretreated before hypoxia) on Na⁺ currents (including transient and persistent Na⁺ currents) in guinea pig ventricular myocytes during hypoxia by the whole-cell and single-channel patch-clamp techniques. Whole-cell recordings showed that the mean current density of I _NaT in the hypoxia group decreased from the control value of 40.2142 ± 1.7735 to 27.1663 ± 1.8441 pA/pF and current density of I _NaP increased from 0.3987 ± 0.0474 to 1.1854 ± 01994 pA/pF (n = 9, P < 0.05 vs. control) at 15 min. However, when vitamin C was administered before hypoxia as pretreatment, I _NaT and I _NaP varied moderately (mean current density of I _NaT decreasing from 41.6038 ± 2.9762 to 34.6341 ± 1.9651 pA/pF and current density of I _NaP increasing from 0.3843 ± 0.0636 to 0.6734 ± 0.1057 pA/pF; n = 9, P < 0.05 vs. hypoxia group). Single-channel recordings (cell-patched) showed that the mean open probability and open time of I _NaP increased significantly in both groups at hypoxia 15 min. However, the increased current values of the hypoxia group were still marked at hypoxia 15 min (n = 9, P < 0.05 vs. vitamin C + hypoxia group). Our results indicate that vitamin C can attenuate the disturbed effects of hypoxia on Na⁺ currents (I _NaT and I _NaP) of cardiac myocytes in guinea pigs effectively.     

Control of the rate of phosphocreatine resynthesis after exercise in trained and untrained human quadriceps muscles

We examined the effect of differences in exercise intensity on the time constant (t _c) of phosphocreatine (PCr) resynthesis after exercise and the relationships betweent _c and maximal oxygen uptake (VO_2max) in endurance-trained runners (n = 5) and untrained controls (n = 7) (average VO_2max = 66.2 and 52.0 ml · min^–1 · kg^–1, respectively). To measure the metabolism of the quadriceps muscle using phosphorus nuclear magnetic resonance spectroscopy, we developed a device which allowed knee extension exercise inside a magnet. All the subjects performed four types of exercise: light, moderate, severe and exhausting. The end-exercise PCr: [PCr + inorganic phosphate (P_i)] ratio decreased significantly with the increase in the exercise intensity (P < 0.01). Although there was little difference in the end-exercise pH, adenosine diphosphate concentration ([ADP]) and the lowest intracellular pH during recovery between light and moderate exercise, significant changes were found at the two higher intensities (P < 0.01). These changes for runners were smaller than those for the controls (P < 0.05). The _c remained constant after light and moderate exercise and then lengthened in proportion to the increase in intensity (P < 0.05). The runners had a lowert _c at the same PCr and pH than the controls, particularly at the higher intensity (P < 0.05). There was a significant correlation betweent _c and [ADP] in light exercise and betweent _c and both end-exercise PCr and pH in severe and exhausting exercise (P < 0.05). The threshold of changes in pH andt _c was a PCr: (PCr + P_i) ratio of 0.5. There was a significant negative correlation between the VO_2max andt _c after all levels of exercise (P<0.05).However, in the controls a significant correlation was found in only light and moderate exercise (P < 0.05). These findings suggest the validity of the use oft _c at an end-exercise PCr:(PCr + P_i) ratio of more than 0.5 as a stable index of muscle oxidative capacity and the correlation between local and general aerobic capacity. Moreover, endurance-trained runners are characterized by the faster PCr resynthesis at the same PCr and intracellular pH.     

Consequences of rearing feeding programme on the performance of rabbit females from 1st to 2nd parturition

To evaluate how rearing programmes could affect resources allocation and reproductive performance of primiparous rabbit females, a total of 118 rabbit females were used to evaluate the effects of five rearing feeding programmes on their performance from 1st to 2nd parturition: CAL, fed ad libitum C diet (11.0 MJ digestible energy (DE), 114 g digestible protein (DP) and 358 g NDF/kg dry matter (DM) until 1st parturition; CR, fed ad libitum with C diet until 12 weeks of age and then C diet restricted (140 g/day) until 1st parturition; F, fed ad libitum with F diet (8.7 MJ DE, 88 g DP and 476 NDF/kg DM) until 1st parturition; FC, fed with F diet ad libitum until 16 weeks of age, and C diet ad libitum until 1st parturition; FCF, fed with F diet ad libitum until 16 weeks of age, then C diet ad libitum until 20 weeks and then F diet ad libitum until 1st parturition. From 1st parturition, C diet was ad libitum offered to all the experimental groups until 2nd parturition. CAL females presented lower feed intake than females of F, FC and FCF groups in the 1^st week of lactation (on av. −16.6%; P<0.05). During 1st lactation, the perirenal fat thickness change in CAL females was not different from 0 (+0.02 mm), while in the other four groups it increased (on av. +0.44 mm; P<0.05). Plasma of females fed with F diet during rearing (F, FC and FCF) had lower non-esterified fatty acids content than those exclusively fed with C diet (–0.088 and –0.072 mmol/l compared to CAL and CR, respectively; P<0.05). FCF litters had higher weight than F litters at day 21 of lactation (+247 g; P<0.05), but FCF litter had significantly lower weight than FC litters at weaning (+170 g; P<0.05). CR females had the shortest average interval between the 1st and 2nd parturition (49 days) and FCF females the longest (+ 9 days compared to CR; P<0.05). At 2nd parturition, liveborn litters of F females were larger and heavier than litters of FCF females (+2.22 kits and +138 g; P<0.05), probably due to the lower mortality at birth of F litters (–16.5 percentage points; P<0.05). In conclusion, rearing females on fibrous diets seems to increase the ability of primiparous rabbit females to obtain resources, especially at the onset of lactation.     

Exercise- and methylcholine-induced sweating responses in older and younger men: effect of heat acclimation and aerobic fitness

 The purpose of this investigation was to examine the effects of aging and aerobic fitness on exercise- and methylcholine-induced sweating responses during heat acclimation. Five younger [Y group – age: 23±1 (SEM) years; maximal oxygen consumption (V.O_2max): 47±3 ml·kg^–1·min^–1], four highly fit older (HO group – 63±3 years; 48±4 ml·kg^–1·min^–1) and five normally fit older men (NO group – 67±3 years; 30±1 ml·kg^–1·min^–1) who were matched for height, body mass and percentage fat, were heat acclimated by daily cycle exercise (≈35% V.O_2max for 90 min) in a hot (43°C, 30% RH) environment for 8 days. The heat acclimation regimen increased performance time, lowered final rectal temperature (T _re) and percentage maximal heart rate (%HR_max), improved thermal comfort and decreased sweat sodium concentration similarly in all groups. Although total body sweating rates (M._sw) during acclimation were significantly greater in the Y and HO groups than in the NO group (P<0.01) (because of the lower absolute workload in the NO group), the M._sw did not change in all groups with the acclimation sessions. Neither were local sweating rates (m. _sw) on chest, back, forearm and thigh changed in all groups by the acclimation. The HO group presented greater forearm m. _sw (30–90 min) values and the Y group had greater back and thigh m. _sw (early in exercise) values, compared to the other groups (P<0.001). In a methylcholine injection test on days immediately before and after the acclimation, the order of sweat output per gland (SGO) on chest, back and thigh was Y>HO>NO, and on the forearm Y=HO>NO. No group differences were observed for activated sweat gland density at any site. The SGO at the respective sites increased in the post-acclimation test regardless of group (P<0.01), but on the thigh the magnitude of the increase was lower in the NO (P<0.02) and HO (P=0.07) groups than in the Y group. These findings suggest that heat tolerance and the improvement with acclimation are little impaired not only in highly fit older but also normally fit older men, when the subjects exercised at the same relative exercise intensity. Furthermore, the changes induced by acclimation appear associated with an age-related decrease in V.O_2max. However methylcholine-activated SGO and the magnitude of improvement of SGO with acclimation are related not only to V.O_2max but also to aging, suggesting that sensitivity to cholinergic stimulation decreases with aging. Received: 8 May 1998/Accepted: 5 October 1998     

Prooxidant/Antioxidant Balance in Hypoxia: A Cross-Over Study on Normobaric vs. Hypobaric “Live High-Train Low”

“Live High-Train Low” (LHTL) training can alter oxidative status of athletes. This study compared prooxidant/antioxidant balance responses following two LHTL protocols of the same duration and at the same living altitude of 2250 m in either normobaric (NH) or hypobaric (HH) hypoxia. Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocols in a cross-over and randomized manner: Living altitude (P_IO₂ = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg in NH and HH, respectively); training “natural” altitude (~1000–1100 m) and training loads were precisely matched between both LHTL protocols. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP) and nitrotyrosine] and antioxidant markers [ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD) and catalase], NO metabolism end-products (NOx) and uric acid (UA) were determined before (Pre) and after (Post) the LHTL. Cumulative hypoxic exposure was lower during the NH (229 ± 6 hrs.) compared to the HH (310 ± 4 hrs.; P<0.01) protocol. Following the LHTL, the concentration of AOPP decreased (-27%; P<0.01) and nitrotyrosine increased (+67%; P<0.05) in HH only. FRAP was decreased (-27%; P<0.05) after the NH while was SOD and UA were only increased following the HH (SOD: +54%; P<0.01 and UA: +15%; P<0.01). Catalase activity was increased in the NH only (+20%; P<0.05). These data suggest that 18-days of LHTL performed in either NH or HH differentially affect oxidative status of athletes. Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH.     

A Study of High-Altitude Hypoxia-Induced Cell Stress in Murine Model

We evaluated the effects of high-altitude hypoxic stress in the murine model. For this purpose, 36 CR-mice in group A were maintained at the altitude of 3,820?m for hypoxia-induced factor (HIF)-1?? expression analysis by immunohistochemistry. The 36 Wistar rats in group B were maintained in low-pressure (400?C420?kPa) oxygen chamber, and the effects of hypoxia on myocardial mitochondria were studied. In the 36 CR-mice of group C, plasma vascular endothelial growth factor (VEGF) levels were determined using strept?Cavidin?Cbiotin complex/diaminobenzidine method after exposure to different altitudes/O₂-concentrations. The data show that in experimental group A1, endothelin (ET)-1?? concentrations gradually increased whereas HIF-1?? expression in myocardial cells was higher (P?<?0.01) than in control group A2. In rats of group B, the myocardial mitochondria numbers were reduced during the initial phase of acute stress response to hypoxia and cellular injury but, later, mitochondrial numbers were restored to normal values. In mice of experimental group C1, plasma VEGF concentrations increased under hypoxia, which were significantly higher (P?<?0.01) than those of control group C2. We, therefore, concluded that high-altitude hypoxia: (i) induced HIF-1?? expression; (ii) prompted adaptation/acclimatization after initial stress and cellular injury; and (iii) enhanced VEGF expression in murine.