Exercise-Induced Norepinephrine Decreases Circulating Hematopoietic Stem and Progenitor Cell Colony-Forming Capacity

A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/−4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (F_iO₂<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.     

Increased blood ammonia in hypoxia during exercise in humans

The effect of acute hypoxia on blood concentration of ammonia ([NH3]b) and lactate (la-]b) was studied during incremental exercise(IE), and two-step constant workload exercises (CE). Fourteen endurance-trained subjects performed incremental exercise on a cycle ergometer under normoxic (21% O2) and hypoxic (10.4% O2) conditions. Eight endurance-trained subjects performed two-step constant workload exercise at sea level and at a simulated altitude of 5000 m (hypobaric chamber, P(B)=405 Torr; P(O2)=85 Torr) in random order. In normoxia, the first step lasted 25 minutes at an intensity of 85 % of the individual ventilatory anaerobic threshold (AT(vent), ind) at sea level. This reduced workload was followed by a second step of 5 minutes at 115% of their AT(vent), ind. This test was repeated into a hypobaric chamber, at a simulated altitude of 5,000 m. The first step in hypoxia was at an intensity of 65 % of AT(vent), ind., whereas workload for the second step at simulated altitude was the same as that of the first workload in normoxia (85 % of AT(vent), ind). During IE, [NH3]b and [la-]b were significantly higher in hypoxia than in normoxia. Increases in these metabolites were highly correlated in each condition. The onset of [NH3]b and [la-]b accumulation occurred at different exercise intensity in normoxia (181W for lactate and 222W for ammonia) and hypoxia (100W for lactate and 140W for ammonia). In both conditions, during CE, [NH3]b showed a significant increase during each of the two steps, whereas [la-]b increased to a steady-state in the initial step, followed by a sharp increase above 4 mM x L(-1) during the second. Although exercise intensity was much lower in hypoxia than in normoxia, [NH3]b was always higher at simulated altitude. Thus, for the same workload, [NH3]b in hypoxia was significantly higher (p<0.05) than in normoxia. Our data suggest that there is a close relationship between [NH3]b and [la-]b in normoxia and hypoxia during graded intensity exercises. The accumulation of ammonia in blood is independent of that of lactate during constant intense exercise. Hypoxia increases the concentration of ammonia in blood during exercise.     

Mild hypobaric hypoxia influences splenic proliferation during the later phase of stress erythropoiesis

Tissue trauma and hemorrhagic shock are common battlefield injuries that can induce hypoxia, inflammation, and/or anemia. Inflammation and hypoxia can initiate adaptive mechanisms, such as stress erythropoiesis in the spleen, to produce red blood cells and restore the oxygen supply. In a military context, mild hypobaric hypoxia—part of the environmental milieu during aeromedical evacuation or en route care—may influence adaptive mechanisms, such as stress erythropoiesis, and host defense. In the present study, healthy (control), muscle trauma, and polytrauma (muscle trauma and hemorrhagic shock) mice were exposed to normobaric normoxia or hypobaric hypoxia for ∼17.5 h to test the hypothesis that hypobaric hypoxia exposure influences splenic erythropoiesis and splenic inflammation after polytrauma. This hypothesis was partially supported. The polytrauma + hypobaric hypoxia group exhibited more splenic neutrophils, fewer total spleen cells, and fewer splenic proliferating cells than the polytrauma+normobaric normoxia group; however, no splenic erythroid cell differences were detected between the two polytrauma groups. We also compared splenic erythropoiesis and myeloid cell numbers among control, muscle trauma, and polytrauma groups. More reticulocytes at 1.7 days (40 h) post-trauma (dpt) and neutrophils at 4 dpt were produced in the muscle trauma mice than corresponding control mice. In contrast to muscle trauma, polytrauma led to a reduced red blood cell count and elevated serum erythropoietin levels at 1.7 dpt. There were more erythroid subsets and apoptotic reticulocytes in the polytrauma mice than muscle trauma mice at 4 and 8 dpt. At 14 dpt, the red blood cell count of the polytrauma + normobaric normoxia mice was 12% lower than that of the control + normobaric normoxia mice; however, no difference was observed between polytrauma + hypobaric hypoxia and control + hypobaric hypoxia mice. Our findings suggest muscle trauma alone induces stress erythropoiesis; in a polytrauma model, hypobaric hypoxia exposure may result in the dysregulation of splenic cells, requiring a treatment plan to ensure adequate immune functioning.     

Chemoreflex and metaboreflex control during static hypoxic exercise

To investigate the effects of muscle metaboreceptor activation during hypoxic static exercise, we recorded muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, ventilation, and blood lactate in 13 healthy subjects (22 +/- 2 yr) during 3 min of three randomized interventions: isocapnic hypoxia (10% O(2)) (chemoreflex activation), isometric handgrip exercise in normoxia (metaboreflex activation), and isometric handgrip exercise during isocapnic hypoxia (concomitant metaboreflex and chemoreflex activation). Each intervention was followed by a forearm circulatory arrest to allow persistent metaboreflex activation in the absence of exercise and chemoreflex activation. Handgrip increased blood pressure, MSNA, heart rate, ventilation, and lactate (all P < 0.001). Hypoxia without handgrip increased MSNA, heart rate, and ventilation (all P < 0.001), but it did not change blood pressure and lactate. Handgrip enhanced blood pressure, heart rate, MSNA, and ventilation responses to hypoxia (all P < 0.05). During circulatory arrest after handgrip in hypoxia, heart rate returned promptly to baseline values, whereas ventilation decreased but remained elevated (P < 0.05). In contrast, MSNA, blood pressure, and lactate returned to baseline values during circulatory arrest after hypoxia without exercise but remained markedly increased after handgrip in hypoxia (P < 0.05). We conclude that metaboreceptors and chemoreceptors exert differential effects on the cardiorespiratory and sympathetic responses during exercise in hypoxia.     

Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses

Leukocyte responsiveness to LPS is dependent upon CD14 and receptors of the Toll-like receptor (TLR) family. Neutrophils respond to LPS, but conflicting data exist regarding LPS responses of eosinophils and basophils, and expression of TLRs at the protein level in these granulocyte lineages has not been fully described. We examined the expression of TLR2, TLR4, and CD14 and found that monocytes expressed relatively high levels of cell surface TLR2, TLR4, and CD14, while neutrophils also expressed all three molecules, but at low levels. In contrast, basophils expressed TLR2 and TLR4 but not CD14, while eosinophils expressed none of these proteins. Tested in a range of functional assays including L-selectin shedding, CD11b up-regulation, IL-8 mRNA generation, and cell survival, neutrophils responded to LPS, but eosinophils and basophils did not. In contrast to previous data, we found, using monocyte depletion by negative magnetic selection, that neutrophil responses to LPS were heavily dependent upon the presence of a very low level of monocytes, and neutrophil survival induced by LPS at 22 h was monocyte dependent. We conclude that LPS has little role in the regulation of peripheral blood eosinophil and basophil function, and that, even in neutrophils, monocytes orchestrate many previously observed leukocyte LPS response patterns.     

Leukocytosis occurs in response to resistance exercise in men

The purpose of this study was to determine the effects of a single bout of resistance exercise on immune cell numbers of moderately active men. Subjects were 16 male volunteers (mean +/- standard deviation [SD] age 30 +/- 7 years, height 180.1 +/- 7.0 cm, mass 83.97 +/- 10.33 kg); 8 were randomly assigned to treatment and 8 to control groups. Treatment was a common resistance training routine (3 sets of 8-10 repetitions at 75% of 1 repetition maximum) of 8 large muscle mass exercises using resistance machines. Blood samples were drawn before exercise and at 0 minutes (P0), 15 minutes (P15), and 30 minutes (P30) postexercise. Control subjects sat quietly in the training facility; blood was drawn at the same intervals as treatment. Leukocyte and lymphocyte (LY) subpopulation numbers were determined. Statistical analysis was analysis of variance (ANOVA) (repeated measures, p < or = 0.050) and multiple comparisons (Dunn method) to isolate variability. All leukocyte subpopulations, except basophils (BA) and eosinophils (EO), increased and counts declined by P15 and P30. Only neutrophils (NE) did not return to preexercise levels by P30. The majority of resistance exercise induced leukocytosis was due to an increase in circulating LY (natural killer cells increased most, CD4+/CD8+ ratio unchanged) and monocytes (MO). The transient, inconsequential immune cell population responses to resistance exercise are similar to those during aerobic activity. The lack of large alterations in and rapid recovery from cell number changes suggests that resistance exercise is not immunosuppressive.     

Effects of low-intensity resistance exercise under acute systemic hypoxia on hormonal responses

Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p ≤ 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p ≤ 0.05). The GH significantly increased only after the HR trial (p ≤ 0.05). The NE and testosterone significantly increased after the exercises in both trials (p ≤ 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season.     

Impact of Exercise and Moderate Hypoxia on Glycemic Regulation and Substrate Oxidation Pattern

Objective

We examined metabolic and endocrine responses during rest and exercise in moderate hypoxia over a 7.5 h time courses during daytime.

Methods

Eight sedentary, overweight men (28.6±0.8 kg/m²) completed four experimental trials: a rest trial in normoxia (FiO₂ = 20.9%, NOR-Rest), an exercise trial in normoxia (NOR-Ex), a rest trial in hypoxia (FiO₂ = 15.0%, HYP-Rest), and an exercise trial in hypoxia (HYP-Ex). Experimental trials were performed from 8:00 to 15:30 in an environmental chamber. Blood and respiratory gas samples were collected over 7.5 h. In the exercise trials, subjects performed 30 min of pedaling exercise at 60% of VO₂max at 8:00, 10:30, and 13:00, and rested during the remaining period in each environment. Standard meals were provided at 8:30, 11:00, and 13:30.

Results

The areas under the curves for blood glucose and serum insulin concentrations over 7.5 h did not differ among the four trials. At baseline, %carbohydrate contribution was significantly higher in the hypoxic trials than in the normoxic trials (P<0.05). Although exercise promoted carbohydrate oxidation in the NOR-Ex and HYP-Ex trials, %carbohydrate contribution during each exercise and post-exercise period were significantly higher in the HYP-Ex trial than in the NOR-Ex trial (P<0.05).

Conclusion

Three sessions of 30 min exercise (60% of VO₂max) in moderate hypoxia over 7.5 h did not attenuate postprandial glucose and insulin responses in young, overweight men. However, carbohydrate oxidation was significantly enhanced when the exercise was conducted in moderate hypoxia.     

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

Background

Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.

Methods

Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂ = 80%) and hyperoxic (FiO₂ = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.

Results

Hypoxia enhanced hyperpnoea-induced P_di,tw and P_ga,tw reductions both immediately after hyperpnoea (P_di,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (P_di,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in P_di,tw or P_ga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.

Conclusions

These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂ transport as during exercise in altitude or in hypoxemic patients.     

The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise

Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO₂ to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO₂ and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO₂ and O₂ chemoreception on the regulation ventilation (E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF), E, end-tidal PCO₂, respiratory compensation threshold (RC) and ventilatory response to exercise (E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO₂ = 0.10) with and without augmenting the fraction of inspired CO₂ (FICO₂). During exercise in normoxia, augmenting FICO₂ elevated MCAv throughout exercise and lowered both RC onset andE slope below RC (P<0.05). In hypoxia, MCAv and E slope below RC during exercise were elevated, while the onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO₂ in hypoxia increased E at RC (P<0.05) but no difference was observed in RC onset, MCAv, or E slope below RC (P>0.05). The E slope above RC was unchanged with either hypoxia or augmented FICO₂ (P>0.05). We found augmenting FICO₂ increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the ‘normal’ cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO₂. Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO₂ is blunted.     

An evaluation of the concept of living at moderate altitude and training at sea level

Despite equivocal findings about the benefit of altitude training, current theory dictates that the best approach is to spend several weeks living at > or =2500 m but training near sea level. This paper summarizes six studies in which we used simulated altitude (normobaric hypoxia) to examine: (i) the assumption that moderate hypoxia compromises training intensity (two studies); and (ii) the nature of physiological adaptations to sleeping in moderate hypoxia (four studies). When submaximal exercise was >55% of sea level maximum oxygen uptake (VO2max), 1800 m simulated altitude significantly increased heart rate, blood lactate and perceived exertion of skiers. In addition, cyclists self-selected lower workloads during high-intensity exercise in hypoxia (2100 m) than in normoxia. Consequently, our findings partially confirm the rationale for 'living high, training low'. In the remaining four studies, serum erythropoietin increased 80% in the early stages of hypoxic exposure, but the reticulocyte response did not significantly exceed that of control subjects. There was no significant increase in haemoglobin mass (Hb(mass)) and VO2max tended to decrease. Performance in exercise tasks lasting approximately 4 min showed a non-significant trend toward improvement (1.0+/-0.4% vs. 0.1+/-0.4% for a control group; P=0.13 for group x time interaction). We conclude that sleeping in moderate hypoxia (2650-3000 m) for up to 23 days may offer practical benefit to elite athletes, but that any effect is not likely due to increased Hb(mass) or VO2max.     

Metabolic effects of exposure to hypoxia plus cold at rest and during exercise in humans

To determine effects on metabolic responses, subjects were exposed to four environmental conditions for 90 min at rest followed by 30 min of exercise: breathing room air with an ambient temperature of 25 degrees C (NN); breathing room air with an ambient temperature of 8 degrees C (NC); hypoxia (induced by breathing 12% O2 in N2) with a neutral temperature (HN); and hypoxia in the cold (HC). Hypoxia increased heart rate (HR), systolic blood pressure (SBP), pulmonary ventilation (VE), respiratory exchange ratio (R), blood lactate, and perceived exertion during exercise while depressing rectal temperature (Tre) and O2 uptake (VO2). Cold exposure elevated SBP, diastolic blood pressure (DBP), VE, VO2, blood glucose, and blood glycerol but decreased HR, Tre, and R. Shivering and DBP were higher and Tre was lower in HC compared with NC. HR, SBP, VE, R, and lactate tended to be higher in HC compared with NC, whereas VO2 and blood glycerol tended to be depressed. These results suggest that cold exposure during hypoxia results in an increased reliance on shivering for thermogenesis at rest whereas, during exercise, heat loss is accelerated.     

Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise

Chronic reductions in tissue O(2) tension (hypoxia) are associated with muscle atrophy and blunted hypertrophic responses to resistance exercise (RE) training. However, the effect of hypoxia on muscle protein synthesis (MPS) at rest and after RE is unknown. In a crossover study, seven healthy men (21.4 ± 0.7 yr) performed unilateral leg RE (6 × 8 repetitions at 70% 1-repetition maximum) under normoxic (20.9% inspired O(2)) and normobaric hypoxic (12% inspired O(2) for 3.5 h) postabsorptive conditions. Immediately after RE the rested leg was biopsied, and a primed continuous infusion of [1,2-(13)C(2)]leucine was maintained for 2.5 h before final biopsies from both legs to measure tracer incorporation and signaling responses (i.e., ribosomal S6 kinase 1). After 3.5 h of hypoxia, MPS was not different from normoxia in the rested leg (normoxia 0.033 ± 0.016 vs. hypoxia 0.043 ± 0.016%/h). MPS increased significantly from baseline 2.5 h after RE in normoxia (0.033 ± 0.016 vs. 0.104 ± 0.038%/h) but not hypoxia (0.043 ± 0.016 vs. 0.060 ± 0.063%/h). A significant linear relationship existed between MPS 2.5 h after RE in hypoxia and mean arterial blood O(2) saturation during hypoxia (r(2) = 0.49, P = 0.04). Phosphorylation of p70S6K(Thr389) remained unchanged in hypoxia at rest but increased after RE in both normoxia and hypoxia (2.6 ± 1.2-fold and 3.4 ± 1.1-fold, respectively). Concentrations of the hypoxia-responsive mTOR inhibitor regulated in development and DNA damage-1 were unaltered by hypoxia or RE. We conclude that normobaric hypoxia does not reduce MPS over 3.5 h at rest but blunts the increased MPS response to acute RE to a degree dependent on extant SpO(2).     

Anaerobic energy provision does not limit Wingate exercise performance in endurance-trained cyclists.

The aim of this study was to evaluate the effects of severe acute hypoxia on exercise performance and metabolism during 30-s Wingate tests. Five endurance- (E) and five sprint- (S) trained track cyclists from the Spanish National Team performed 30-s Wingate tests in normoxia and hypoxia (inspired O(2) fraction = 0.10). Oxygen deficit was estimated from submaximal cycling economy tests by use of a nonlinear model. E cyclists showed higher maximal O(2) uptake than S (72 +/- 1 and 62 +/- 2 ml x kg(-1) x min(-1), P < 0.05). S cyclists achieved higher peak and mean power output, and 33% larger oxygen deficit than E (P < 0.05). During the Wingate test in normoxia, S relied more on anaerobic energy sources than E (P < 0.05); however, S showed a larger fatigue index in both conditions (P < 0.05). Compared with normoxia, hypoxia lowered O(2) uptake by 16% in E and S (P < 0.05). Peak power output, fatigue index, and exercise femoral vein blood lactate concentration were not altered by hypoxia in any group. Endurance cyclists, unlike S, maintained their mean power output in hypoxia by increasing their anaerobic energy production, as shown by 7% greater oxygen deficit and 11% higher postexercise lactate concentration. In conclusion, performance during 30-s Wingate tests in severe acute hypoxia is maintained or barely reduced owing to the enhancement of the anaerobic energy release. The effect of severe acute hypoxia on supramaximal exercise performance depends on training background.     

Treadmill Exercise Induces Neutrophil Recruitment into Muscle Tissue in a Reactive Oxygen Species-Dependent Manner. An Intravital Microscopy Study

Intense exercise is a physiological stress capable of inducing the interaction of neutrophils with muscle endothelial cells and their transmigration into tissue. Mechanisms driving this physiological inflammatory response are not known. Here, we investigate whether production of reactive oxygen species is relevant for neutrophil interaction with endothelial cells and recruitment into the quadriceps muscle in mice subjected to the treadmill fatiguing exercise protocol. Mice exercised until fatigue by running for 56.3±6.8 min on an electric treadmill. Skeletal muscle was evaluated by intravital microscopy at different time points after exercise, and then removed to assess local oxidative stress and histopathological analysis. We observed an increase in plasma lactate and creatine kinase (CK) concentrations after exercise. The numbers of monocytes, neutrophils, and lymphocytes in blood increased 12 and 24 hours after the exercise. Numbers of rolling and adherent leukocytes increased 3, 6, 12, and 24 hours post-exercise, as assessed by intravital microscopy. Using LysM-eGFP mice and confocal intravital microscopy technology, we show that the number of transmigrating neutrophils increased 12 hours post-exercise. Mutant gp91^phox-/- (non-functional NADPH oxidase) mice and mice treated with apocynin showed diminished neutrophil recruitment. SOD treatment promoted further adhesion and transmigration of leukocytes 12 hours after the exercise. These findings confirm our hypothesis that treadmill exercise increases the recruitment of leukocytes to the postcapillary venules, and NADPH oxidase-induced ROS plays an important role in this process.     

Effect of Acute Exposure to Moderate Altitude on Muscle Power: Hypobaric Hypoxia vs. Normobaric Hypoxia

When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (P_max) was recorded as the highest P_mean obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to P_max (∼3%) and maximal strength (1RM) (∼6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on P_mean and P_peak in the middle-high part of the curve (≥60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1RM, movement velocity and power during the execution of a force-velocity curve in bench press.     

Mast Cell Survival and Mediator Secretion in Response to Hypoxia

Tissue hypoxia is a consequence of decreased oxygen levels in different inflammatory conditions, many associated with mast cell activation. However, the effect of hypoxia on mast cell functions is not well established. Here, we have investigated the effect of hypoxia per se on human mast cell survival, mediator secretion, and reactivity. Human cord blood derived mast cells were subjected to three different culturing conditions: culture and stimulation in normoxia (21% O₂); culture and stimulation in hypoxia (1% O₂); or 24 hour culture in hypoxia followed by stimulation in normoxia. Hypoxia, per se, did not induce mast cell degranulation, but we observed an increased secretion of IL-6, where autocrine produced IL-6 promoted mast cell survival. Hypoxia did not have any effect on A23187 induced degranulation or secretion of cytokines. In contrast, cytokine secretion after LPS or CD30 treatment was attenuated, but not inhibited, in hypoxia compared to normoxia. Our data suggests that mast cell survival, degranulation and cytokine release are sustained under hypoxia. This may be of importance for host defence where mast cells in a hypoxic tissue can react to intruders, but also in chronic inflammations where mast cell reactivity is not inhibited by the inflammatory associated hypoxia.     

版纳鱼螈外周血细胞观察

以濒危两栖动物版纳鱼螈(Ichthyophis bannanica)为材料,应用瑞氏-姬姆萨混合染色法与血细胞计数法观察并统计了版纳鱼螈各种外周血细胞的形态特征和数量比例.结果表明,版纳鱼螈的外周血液中红细胞数量较多,呈卵圆形、椭圆形、梭形和梨形,平均含量为2.57 ×105个/mm3.白细胞数量较少,多呈近圆形,平均含量为0.72×103个/mm3.白细胞中,淋巴细胞最多,其次为单核细胞、嗜中性粒细胞、嗜碱性粒细胞和嗜酸性粒细胞.血栓细胞数量较少,常数个集合在一起.同时,将此研究结果与鱼类、爬行类和其他两栖类的血细胞比较,进而探讨了版纳鱼螈的进化地位.     

Investigation of glucose catabolism in hypoxic Mcf 7 breast cancer culture

Hypoxia plays an important role in tumor phenotype and progression and alters glycolysis, with changes in signaling pathways that develop in response to hypoxia. In this study, the effects of oxygen (normoxia/hypoxia) and of glucose levels on the glucose metabolism was investigated in MCF-7 cancer cells. Under either normoxia or hypoxia conditions, the cells were exposed to glucose at different concentrations (0, 5.5, 15 or 55 mM) for either 3, 6, 12, 24 or 48 h. In all groups, cell viability, levels of key enzymes reflecting glycolytic metabolism in cell lysates, glucose consumed in the medium and extracellular lactate levels and wound closure percentages were determined. In hypoxic cells, intracellular consumption of glucose, and extracellular lactate levels due to increased glucose concentration were observed to be higher (compared to normoxia) and as a result of prolonged exposure to hypoxia, cells were observed to develop resistance to the prolonged exposure to hypoxia. The number of glycolytic enzymes obtained at different levels proved that cells had different potential capacities and changing mechanisms for the metabolic needs of the cell depending on the glucose amount in the medium and time in adapting to the oxygen tension. This study showed that there was an important interaction between hypoxia and glucose metabolism in general, and it was concluded that metabolic processes activated by hypoxia could offer new therapeutic targets.     

Severe hypoxia decreases oxygen uptake relative to intensity during submaximal graded exercise

The effect of severe acute hypoxia (fractional concentration of inspired oxygen equalled 0.104) was studied in nine male subjects performing an incremental exercise test. For power outputs over 125 W, all the subjects in a state of hypoxia showed a decrease in oxygen consumption ( O₂) relative to exercise intensity compared with normoxia (P < 0.05). This would suggest an increased anaerobic metabolism as an energy source during hypoxic exercise. During submaximal exercise, for a given O₂, higher blood lactate concentrations were found in hypoxia than in normoxia (P < 0.05). In consequence, the onset of blood lactate accumulation (OBLA) was shifted to a lower O₂ ( O₂ 1.77 l·min^–1 in hypoxia vs 3.10 l·min^–1 in normoxia). Lactate concentration increases relative to minute ventilation ( _E) responses were significantly higher during hypoxia than in normoxia (P < 0.05). At OBLA, _E during hypoxia was 25% lower than in the normoxic test. This study would suggest that in hypoxia subjects are able to use an increased anaerobic metabolism to maintain exercise performance.