Intermittent normobaric hypoxia does not alter performance or erythropoietic markers in highly trained distance runners.

This study was designed to test the hypothesis that intermittent normobaric hypoxia at rest is a sufficient stimulus to elicit changes in physiological measures associated with improved performance in highly trained distance runners. Fourteen national-class distance runners completed a 4-wk regimen (5:5-min hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of intermittent normobaric hypoxia (Hyp) or placebo control (Norm) at rest. The experimental group was exposed to a graded decline in fraction of inspired O2: 0.12 (week 1), 0.11 (week 2), and 0.10 (weeks 3 and 4). The placebo control group was exposed to the same temporal regimen but breathed fraction of inspired O2 of 0.209 for the entire 4 wk. Subjects were matched for training history, gender, and baseline measures of maximal O2 uptake and 3,000-m time-trial performance in a randomized, balanced, double-blind design. These parameters, along with submaximal treadmill performance (economy, heart rate, lactate, and ventilation), were measured in duplicate before, as well as 1 and 3 wk after, the intervention. Hematologic indexes, including serum concentrations of erythropoietin and soluble transferrin receptor and reticulocyte parameters (flow cytometry), were measured twice before the intervention, on days 1, 5, 10, and 19 of the intervention, and 10 and 25 days after the intervention. There were no significant differences in maximal O2 uptake, 3,000-m time-trial performance, erythropoietin, soluble transferrin receptor, or reticulocyte parameters between groups at any time. Four weeks of a 5:5-min normobaric hypoxia exposure at rest for 70 min, 5 days/wk, is not a sufficient stimulus to elicit improved performance or change the normal level of erythropoiesis in highly trained runners.     

Dopamine does not limit fetal cerebrovascular responses to hypoxia.

Dopamine is used clinically to stabilize mean arterial blood pressure (MAP) in sick infants. One goal of this therapeutic intervention is to maintain adequate cerebral blood flow (CBF) and perfusion pressure. High-dose intravenous dopamine has been previously demonstrated to increase cerebrovascular resistance (CVR) in near-term fetal sheep. We hypothesized that this vascular response might limit cerebral vasodilatation during acute isocapnic hypoxia. We studied nine near-term chronically catheterized unanesthetized fetal sheep. Using radiolabeled microspheres to measure fetal CBF, we calculated CVR at baseline, during fetal hypoxia, and then with the addition of an intravenous dopamine infusion at 2.5, 7.5, and 25 microg.kg(-1).min(-1) while hypoxia continued. During acute isocapnic fetal hypoxia, CBF increased 73.0 +/- 14.1% and CVR decreased 38.9 +/- 4.9% from baseline. Dopamine infusion at 2.5 and 7.5 microg.kg(-1).min(-1), begun during hypoxia, did not alter CVR or MAP, but MAP increased when dopamine infusion was increased to 25 microg.kg(-1).min(-1). Dopamine did not alter CBF or affect the CBF response to hypoxia at any dose. However, CVR increased at a dopamine infusion rate of 25 microg.kg(-1).min(-1). This increase in CVR at the highest dopamine infusion rate is likely an autoregulatory response to the increase in MAP, similar to our previous findings. Therefore, in chronically catheterized unanesthetized near-term fetal sheep, dopamine does not alter the expected cerebrovascular responses to hypoxia.     

Antioxidant intervention does not affect the response of plasma erythropoietin to short-term normobaric hypoxia in humans.

Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac-alpha-tocopherol (800 mg/day for 3 wk) and alpha-lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum alpha-tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary Po(2) declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.     

AMP does not induce torpor

Torpor, a state characterized by a well-orchestrated reduction of metabolic rate and body temperature (T(b)), is employed for energetic savings by organisms throughout the animal kingdom. The nucleotide AMP has recently been purported to be a primary regulator of torpor in mice, as circulating AMP is elevated in the fasted state, and administration of AMP causes severe hypothermia. However, we have found that the characteristics and parameters of the hypothermia induced by AMP were dissimilar to those of fasting-induced torpor bouts in mice. Although administration of AMP induced hypothermia (minimum T(b) = 25.2 +/- 0.6 degrees C) similar to the depth of fasting-induced torpor (24.9 +/- 1.5 degrees C), ADP and ATP were equally effective in lowering T(b) (minimum T(b): 24.8 +/- 0.9 degrees C and 24.0 +/- 0.5 degrees C, respectively). The maximum rate of T(b) fall into hypothermia was significantly faster with injection of adenine nucleotides (AMP: -0.24 +/- 0.03; ADP: -0.24 +/- 0.02; ATP: -0.25 +/- 0.03 degrees C/min) than during fasting-induced torpor (-0.13 +/- 0.02 degrees C/min). Heart rate decreased from 755 +/- 15 to 268 +/- 17 beats per minute (bpm) within 1 min of AMP administration, unlike that observed during torpor (from 646 +/- 21 to 294 +/- 19 bpm over 35 min). Finally, the hypothermic effect of AMP was blunted with preadministration of an adenosine receptor blocker, suggesting that AMP action on T(b) is mediated via the adenosine receptor. These data suggest that injection of adenine nucleotides into mice induces a reversible hypothermic state that is unrelated to fasting-induced torpor.     

Cardiorespiratory responses to prolonged normobaric inhalatory hypoxia in healthy men

Changes in the cardiorespiratory indicators due to the prolonged (25 min) inhalation of a respiratory mixture with an exponentially falling (from 20.9% to 10%) oxygen concentration were studied in healthy young men. The efficiency of oxygen uptake (as the ventilatory equivalent of O₂) in the lungs has been shown to fall particularly promptly (within the first 2–5 min). Individual manifestations of this fall were variable (ranging from 22 to 84% of the baseline data) and driven, to a considerable degree, by the subject’s current level of alveolar ventilation, mobilizing its urgent reserve to improve the ventilation-perfusion relations in the lungs. The subsequent response as a growth in the heart rate (HR) recorded in 100% of cases was delayed relative to the start of hypoxic exposure and combined with increased hypoxemia marked as a decrease in the blood oxygen saturation of hemoglobin. The individual HR growth in response to hypoxia ranged from 8 to 43% of the baseline level and was significantly related to the current level of diastolic arterial blood pressure. The hypoxic ventilatory response was expressed only in 71% of cases, including the 15% when it was reversed (decreased) against the background of a concomitant decrease in the respiratory frequency.     

Naloxone does not affect ventillatory responses to hypoxia and hypercapnia in rats

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) or naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.     

The effects of normobaric hypoxia on the leukocyte responses to resistance exercise

There is growing interest in the use of systemic hypoxia to improve the training adaptations to resistance exercise. Hypoxia is a well-known stimulator of the immune system, yet the leukocyte responses to this training modality remain uncharacterised. The current study characterised the acute leukocyte responses to resistance exercise in normobaric hypoxia. The single-blinded, randomised trial recruited 13 healthy males aged 18–35 years to perform a bout of resistance exercise in normobaric hypoxia (14.4% O₂; n = 7) or normoxia (20.9% O₂; n = 6). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% 1-repetition maximum. Oxygen saturation, rating of perceived exertion and heart rate were measured during the session. Venous blood was sampled before and up to 24 hours post-exercise to quantify blood lactate, glucose and leukocytes including neutrophils, lymphocytes, monocytes, eosinophils and basophils. Neutrophils were higher at 120 and 180 minutes post-exercise in hypoxia compared to normoxia (p<0.01), however lymphocytes, monocytes, eosinophils and basophils were unaffected by hypoxia. Oxygen saturation was significantly lower during the four exercises in hypoxia compared to normoxia (p < 0.001). However, there were no differences in blood lactate, heart rate, perceived exertion or blood glucose between groups. Hypoxia amplified neutrophils following resistance exercise, though all other leukocyte subsets were unaffected. Therefore, hypoxia does not appear to detrimentally affect the lymphocyte, monocyte, eosinophil or basophil responses to exercise.     

Streptococcus pneumoniae heat shock protein 70 does not induce human antibody responses during infection

Mouse monoclonal antibodies (mAbs) were developed against Streptococcus pneumoniae in search for potential common pneumococcal proteins as vaccine antigens. mAb 230,B-9 (IgG1) reacted by immunoblotting with a 70-kDa protein which was isolated by immunoaffinity chromatography and subsequent preparative electrophoresis. N-terminal amino acid sequencing showed homology to that of heat shock protein 70 (hsp70). The hsp70 epitope reactive with mAb 230,B-9 was found in all the pneumococci examined as well as in other streptococci and enterococci. The epitope was not expressed in several other examined Gram-positive or -negative bacteria. Pneumococcal hsp70 has by other investigators been proposed to be a vaccine candidate. Binding experiments using flow cytometry showed that the epitope was not surface-exposed on live exponential phase grown S. pneumoniae. Human patient sera did not react with affinity-purified pneumococcal hsp70. Therefore the pneumococcal hsp70 does not seem to be of special interest in a vaccine formulation. The human sera contained antibodies to high molecular proteins co-purified with hsp70. Some of these proteins could be the pneumococcal surface protein A.     

Acute depletion of heme by succinylacetone alters vascular responses but does not induce hypertension

Heme plays a critical role in blood pressure regulation because it is required by a number of enzymes that synthesize vascular modulators, including nitric oxide (NO), carbon monoxide (CO), guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin. The goal of this study was to examine the vascular effects of a short-term depletion of heme achieved through administration of the heme-synthesis inhibitor succinylacetone (SA), an irreversible inhibitor of aminolevulinic acid dehydratase (ALAD). Rats were depleted of heme by using a 4-day treatment with SA. This treatment impacted hemoenzyme function, decreasing renal nitric oxide synthase (NOS) activity (as indicated by decreased in vitro NOS activity), and increasing kidney microsomal heme oxygenase (HO) activity by 27%. SA treatment also resulted in enhanced reduction in blood pressure after infusions of exogenous NO donor MAHMA NONOate (at high dose) and acetylcholine (at low doses). Nevertheless, this SA treatment was insufficient to produce an overt elevation of basal arterial pressure. This latter lack of effect may be the result of multiple compensatory mechanisms for the regulation of blood pressure.