Eur J Appl Physiol. 2006 Jan;96(1):66-77. Epub 2005 Oct 26.
Brugniaux JV, Schmitt L, Robach P, Jeanvoine H, Zimmermann H, Nicolet G, Duvallet A, Fouillot JP, Richalet JP.
Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie EA2363, ARPE, UFR SMBH, Universite Paris 13, 74 rue Marcel Cachin, 93017, Bobigny cedex, France. jbrugniaux@free.fr
The "living high-training low" (LHTL) model is frequently used to enhance aerobic performance. However, the clinical tolerance and acclimatization process to this intermittent exposure needs to be examined. Forty one athletes from three federations (cross-country skiers, n=11; swimmers, n=18; runners, n=12) separately performed a 13 to 18-day training at the altitude of 1,200 m, by sleeping either at 1,200 m (CON) or in hypoxic rooms (HYP), with an O2 fraction corresponding to 2,500 m (5 nights for swimmers and 6 for skiers and runners), 3,000 m (6 nights for skiers, 8 for swimmers and 12 for runners) and 3,500 m (6 nights for skiers). Measurements performed before, 1 or 15 days after training were ventilatory response (HVRe) and desaturation (deltaSaO2e) during hypoxic exercise, an evaluation of cardiac function by echocardiography, and leukocyte count. Lake Louise AMS score and arterial O2 saturation during sleep were measured daily for HYP. Subjects did not develop symptoms of AMS. Mean nocturnal SaO2 decreased with altitude down to 90% at 3,500 m and increased with acclimatization (except at 3,500 m). Leukocyte count was not affected except at 3,500 m. The heart function was not affected by LHTL. Signs of ventilatory acclimatization were present immediately after training (increased HVRe and decreased deltaSaO2e) and had disappeared 15 days later. In conclusion, LHTL was well tolerated and compatible with aerobic training. Comparison of the three patterns of training suggests that a LHTL session should not exceed 3,000 m, for at least 18 days, with a minimum of 12 h day(-1) of exposure.
Gerontology. 2006;52(1):17-23.
Bianchi G, Di Giulio C, Rapino C, Rapino M, Antonucci A, Cataldi A.
Dipartimento di Scienze Biomediche, G. d'Annunzio Chieti e Pescara, Chieti, Italia.
Background: During development and aging, as well as under hypoxia, many cells can adapt to a stressful environment, while others are damaged and die by apoptosis. In particular, intermittent hypoxia, i.e., hypoxia followed by reoxygenation, determines different responses in young and adult myocardia. Objective: In the rat myocardium exposed to hypoxia, the roles played by p53 and p66 Shc proteins in matching, in an age-dependent mode, in stabilizing hypoxia-inducible factor-1alpha (HIF-1alpha), and in preventing its biological activity, which usually induces synthesis of rescue proteins against this stress, were investigated. Methods: Five animals from three groups, each consisting of 10 male Wistar rats, 8 days and 3 and 24 months old, were kept under physiological conditions; 5 young and 5 old rats were exposed to intermittent hypoxic challenges (12 h at 10% O(2) followed by 12 h at 21% O(2)) for 8 days. Pregnant rats were kept for 3 days under hypoxic conditions before delivery, and 5 neonate rats were kept in intermittent hypoxia for 8 days. Left ventricles were excised and processed for TUNEL and Western blotting analyses. Results: HIF-1alpha stabilization by p53 along with decline in Bcl2, substantial caspase-3 expression, and a large number of apoptotic events make the hypoxic young myocardium the most damaged when compared to the neonatal one, in which HIF-1alpha is not stabilized. Moreover, high expression and activation of p66 in hypoxic young and in normoxic old myocardia suggests a pathological increase of the response to oxidative stress in the former and a physiological progressive increase in the latter. Conclusions: The different responses to hypoxic challenge during life show that the young seem the most reactive and damaged, as is well documented by p53-mediated HIF-1alpha stabilization. The neonate, not showing any modification in terms of HIF-1alpha expression and activation, seems 'adapted' to such an environment, since it was maintained in hypoxia 3 days before and 8 days after birth. In the old, increasing p66 expression and tyrosine phosphorylation, probably exerting a slight HIF-1alpha stabilization in the two experimental conditions, provide evidence of longevity and oxidative stress resistance, as suggested by the low number of apoptotic events seen upon hypoxic challenge, and this fact could be due to impairment of oxygen-sensing mechanisms or to adaptation of the cells to apoptosis. Copyright (c) 2006 S. Karger AG, Basel.
Am J Physiol Regul Integr Comp Physiol. 2006 Feb 2; [Epub ahead of print]
Reeves SR, Mitchell GS, Gozal D.
Pediatrics, University of Louisville, Louisville, KY, USA; Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
Acute isocapnic intermittent hypoxia elicits a time-dependent, serotonin-dependent enhancement of phrenic motor output in anesthetized rats, i.e., phrenic long-term facilitation (pLTF). In adult rats, pLTF is enhanced by chronic intermittent hypoxia (CIH). To test the hypothesis that early postnatal CIH induces persistent modifications of ventilation and pLTF, male Sprague-Dawley rat pups were exposed as of the 1st day of life to a CIH profile consisting of alternating room air and 10% oxygen every 90 sec for 30 days during daylight hours (RAIH), or to a comparable exposures consisting of room air throughout (RARA). One month after cessation of CIH, respiratory responses were recorded using whole-body plethysmography and integrated phrenic nerve activity was recorded in urethane-anaesthetized, vagotomized, paralyzed and ventilated rats at baseline and following exposures to three, 5-min hypoxic episodes (FIO2 = 0.11) separated by 5 min hyperoxia (FIO2 = 0.5). RAIH rats displayed greater normoxic ventilation and also increased burst frequency compared to RARA rats (p<0.01). Ventilatory responses to hypoxia and short-term phrenic responses during acute hypoxic challenges were reduced in RAIH (p<0.01). Although pLTF was present in both RAIH and RARA rats, it was diminished in RAIH (minute activity: 74+/-2% in RARA vs. 55+/-5% in RAIH rats at 60 min; p<0.01). Thus, we conclude that early postnatal CIH modifies normoxic and hypoxic ventilatory and phrenic responses that persist at one month after cessation of CIH (i.e., metaplasticity), and markedly differ from previously reported increased neural plasticity changes induced by CIH in adult rats.
Martin DT, Hahn AG.
J Appl Physiol. 2005 Dec 8; [Epub ahead of print]
Ponsot E, Dufour SP, Zoll J, Doutreleau S, N'guessan B, Geny B, Hoppeler H, Lampert E, Mettauer B, Ventura-Clapier R, Richard R.
Service de Physiologie Clinique et des EFR, Departement de Physiologie, Hopital Civil, Strasbourg, France, Metropolitan.
This study investigates whether adaptations of mitochondrial function accompany the improvement of endurance performance capacity observed in well-trained athletes after an intermittent hypoxic training program (IHT). Fifteen endurance trained athletes performed two weekly training sessions on treadmill at vVT2 (velocity associated to the second ventilatory threshold) with FiO2=14.5% (HYP, n=8) or with FiO2=21% (NOR, n=7), integrated into their usual training, for 6 weeks. Before and after training, oxygen uptake and speed at VT2, maximal oxygen uptake (VO2max), time to exhaustion (Tlim) at vVO2max (minimal speed associated with VO2max) were measured and muscle biopsies of Vastus Lateralis were harvested. Muscle oxidative capacities (Vmax) and sensitivity of mitochondrial respiration to ADP (Km) were evaluated on permeabilized muscle fibers. Tlim, VO2 at VT2 and VO2max were significantly improved in HYP (+42%, +8%, +5% respectively) but not in NOR. No increase in muscle oxidative capacity was obtained with either training protocol. However, mitochondrial regulation shifted to a more oxidative profile in HYP only as shown by the increased Km for ADP (NOR: before 476+/-63, after 524+/-62microM, ns; HYP: before 441+/-59, after 694+/-51microM, p<0.05). Thus, including hypoxia sessions into the usual training of athletes qualitatively ameliorates mitochondrial function by increasing the respiratory control by creatine, providing a tighter integration between ATP demand and supply.
Ergonomics. 2005 Sep 15-Nov 15;48(11-14):1535-46.
Morton JP, Cable NT.
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, 15-21 Webster Street, Liverpool L3 2ET, UK. SPSJMORT@livjm.ac.uk
The aim of the present study was to determine whether short-term intermittent hypoxic training would enhance sea level aerobic and anaerobic performance over and above that occurring with equivalent sea level training. Over a 4-week period, two groups of eight moderately trained team sports players performed 30 min of cycling exercise three times per week. One group trained in normobaric hypoxia at a simulated altitude of 2750 m (F(I)O2= 0.15), the other group trained in a laboratory under sea level conditions. Each training session consisted of ten 1-min bouts at 80% maximum workload maintained for 2 min (Wmax) during the incremental exercise test at sea level separated by 2-min active recovery at 50% Wmax. Training intensities were increased by 5% after six training sessions and by a further 5% (of original Wmax) after nine sessions. Pre-training assessments of VO(2max), power output at onset of 4 mM blood lactate accumulation (OBLA), Wmax and Wingate anaerobic performance were performed on a cycle ergometer at sea level and repeated 4-7 d following the training intervention. Following training there were significant increases (p < 0.01) in VO(2max) (7.2 vs. 8.0%), Wmax (15.5 vs. 17.8%), OBLA (11.1 vs. 11.9%), mean power (8.0 vs. 6.5%) and peak power (2.9 vs. 9.3%) in both the hypoxic and normoxic groups respectively. There were no significant differences between the increases in any of the above-mentioned performance parameters in either training environment (p > 0.05). In addition, neither haemoglobin concentration nor haematocrit were significantly changed in either group (p > 0.05). It is concluded that acute exposure of moderately trained subjects to normobaric hypoxia during a short-term training programme consisting of moderate- to high-intensity intermittent exercise has no enhanced effect on the degree of improvement in either aerobic or anaerobic performance. These data suggest that if there are any advantages to training in hypoxia for sea level performance, they would not arise from the short-term protocol employed in the present study.
Am J Physiol Cell Physiol. 2005 Nov 23; [Epub ahead of print]
Chen L, Lu XY, Li J, Fu JD, Zhou ZN, Yang HT.
Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS Chinese Academy of Sciences (CAS& Shanghai Jiao Tong University School of Medicine (SJTUSM Shanghai, China.
We have previously demonstrated that intermittent high altitude (IHA) hypoxia significantly attenuates ischemia-reperfusion (I/R)-induced excessive increase in the resting [Ca(2+)]i. Since the sarcoplasmic reticulum (SR) and Na(+)/Ca(2+) exchange (NCX) play crucial roles in regulating [Ca(2+)]i and both are in dysfunction during I/R, we tested the hypothesis in the present study that IHA hypoxia may prevent I/R-induced Ca(2+) overload by maintainting Ca(2+) homeostasis via SR and NCX mechanisms. We thus determined the dynamics of Ca(2+) transients and cell shortening during preischemia and I/R in ventricular cardiomyocytes from normoxic and IHA hypoxic rats. IHA hypoxia did not affect the preischemic dynamics of Ca(2+) transients and cell shortening, but it significantly suppressed the I/R-induced increase in the resting [Ca(2+)]i and attenuated the depression of the Ca(2+) transients and cell shortening during reperfusion. Moreover, IHA hypoxia significantly attenuated I/R-induced depression of the protein contents of SR Ca(2+) release channels/ryanodine receptors (RyRs) and Ca(2+)-pump ATPase (SERCA2) and SR Ca(2+) release and uptake. In addition, a delayed decay of Ca(2+) transients seen at ischemia was accompanied with markedly inhibited NCX currents, which were prevented by IHA hypoxia. These findings indicate that IHA hypoxia may preserve Ca(2+) homeostasis and contraction by preserving RyRs and SERCA2 proteins and NCX activity during I/R.
J Mol Cell Cardiol. 2006 Jan;40(1):96-106. Epub 2005 Nov 8.
Zhu WZ, Xie Y, Chen L, Yang HT, Zhou ZN.
Laboratory of Hypoxic Cardiovascular Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
The role of mitochondrial permeability transition pore (MPTP) in the mechanism of intermittent high altitude (IHA) hypoxic adaptation is not understood. Therefore, we study whether the protective effect of IHA hypoxia against ischemia-reperfusion injury is accompanied by inhibition of MPTP opening. IHA hypoxia significantly improved the functional recovery of Langendorff hearts on reperfusion and limited infarct size. In isolated myocytes, IHA hypoxia significantly improved the recovery of cell length, lowered ischemia-reperfusion-induced [Ca2+]c and [Ca2+]m overloading. Furthermore, IHA hypoxia accelerated [Ca2+]c decline during reperfusion. Opening the MPTP with atractyloside immediately at reperfusion abolished these cardioprotective effects of IHA hypoxia, but had no appreciable influence on those of normoxic hearts. IHA hypoxia prolongs the time taken to induce MPTP opening and the time taken to induce rigor contracture when myocytes subjected to oxidative stress. The data from isolated mitochondria demonstrated that IHA hypoxia prevented the decrease of ADP/O ratio, the opening of MPTP and the release of cytochrome c from mitochondria at high Ca2+ concentrations (100 and 200 microM). Inhibition of MPTP opening in the first few minutes of reperfusion accelerated [Ca2+]c decline and attenuated [Ca2+]c and [Ca2+]m overloading, which contributed to the cardioprotection of IHA hypoxic adaptation. Enhancement of the tolerance of mitochondria against Ca2+ might underlie the protective mechanism of IHA hypoxia.
Tokai J Exp Clin Med. 2005 Sep;30(3):157-61.
Iwamoto T, Kamiya U, Ishii M, Urano T, Kuwahira I.
Department of Medicine, Tokai University Tokyo Hospital, 1-2-5 yoyogi, Shibuya-ku, Tokyo 151-0053, Japan.
It is not yet clear whether there is an intermittent hypoxia (IHx) threshold to elicit polycythemia and blood pressure elevation, and whether blood hemoglobin concentration ([Hb]) increases with an increase in the hypoxic exposure period. We have previously shown that repetitive exposure to 10% O2 for 60 min/day for up to 5 weeks does not produce polycythemia. In the present study, we evaluated the effect of IHx of 10% O2, 120 min/day for 1, 2, 3 and 4 weeks on [Hb], arterial blood pressure, heart rate and arterial blood gases in the rat. IHx of 10% O2, 120 min/day induced polycythemia at 1 week and produced a time-dependent increase in [Hb] from 0 week to 4 weeks. Arterial blood pressure significantly increased during IHx exposure for 4 weeks probably due to a combination of an increased sympathetic activity as well as increased blood viscosity. The IHx threshold for polycythemia might exist between 60 min/day and 120 min/day in this level of hypoxia.
Bull Exp Biol Med. 2005 Aug;140(2):190-3.
Zarubina IV, Nurmanbetova FN, Shabanov PD.
Department of Pharmacology, Russian Military Medical Academy, St. Petersburg.
The rats were adapted to hypoxic hypoxia by intermittent training in a flow pressure chamber for 3 days. The course of bemithyl treatment (25 mg/kg intraperitoneally, 3 days) started immediately after the 1st day of training. Bemithyl potentiated the adaptive metabolic changes in rat brain induced by repeated hypoxic hypoxia, increased the individual resistance to hypoxia, and produced a long-lasting effect.
Eur J Pediatr Surg. 2005 Oct;15(5):325-32.
Ceylan H, Yuncu M, Gurel A, Armutcu F, Gergerlioglu HS, Bagci C, Demiryurek AT.
Department of Pediatric Surgery, Faculty of Medicine, University of Gaziantep, 27310 Gaziantep, Turkey. halukceylan@yahoo.com
PURPOSE: The precise cause of necrotizing enterocolitis (NEC) is elusive. Ischemia and reperfusion injury of the intestine has been considered to be a major contributing factor for NEC. Ischemic preconditioning is defined as one or more brief periods of ischemia with intermittent reperfusion that protects tissues against a sustained period of subsequent ischemia. Contribution of preconditioning to hypoxia/reoxygenation-induced intestinal injury in newborn rats has not been evaluated previously. METHODS: The study was carried out on 1-day-old Wistar albino rat pups. Whole-body hypoxia and reoxygenation (H/R) was achieved by 10 min hypoxia using 95 % N (2) + 5 % CO (2) followed by 10 min reoxygenation with 100 % oxygen. Whole body hypoxic preconditioning (HP) cycles were performed with 3 min hypoxia and 5 min reoxygenation. Thirty-three pups were randomly allocated into 4 groups. Group 1 served as untreated controls. The pups in group 2 were subjected to H/R only. In groups 3 and 4, 1 cycle and 3 cycles of HP were performed prior to H/R, respectively. Animals were killed at the end of the protocols. Intestine specimens were obtained to determine the histological changes, as well as to measure the tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and xanthine oxidase (XO) and myeloperoxidase (MPO) activities. RESULTS: The microscopic lesions in H/R rat pups were virtually the same as those seen in neonatal NEC, with severe destruction of villi and crypts, in some cases extending to the muscularis. In both HP groups, the lesions were found to be milder. H/R resulted in a marked elevation in MDA and NO levels, and XO and MPO activities compared to the untreated controls. Both 1 cycle and 3 cycles of HP prior to H/R resulted in an obvious decrease in all biochemical parameters. Differences of the biochemical results between both HP groups were not statistically significant. CONCLUSION: This study revealed that whole-body hypoxic preconditioning is beneficial for hypoxia/reoxygenation-induced intestinal injury in newborn rats.
[Article in Ukrainian]
Vavilova HL, Serebrovs'ka TV, Rudyk OV, Bielikova MV, Koliesnikova IeE, Kukoba TV, Sahach VF.
On the mitochondria isolated from the heart tissue of adult rats we studied the sensitivity of mitochondrial permeability transition pore (MPTP) opening to its inductor--phenylarsine oxide (PAO) after mitochondrial swelling, registered by spectrophotometric technique at n = 520 nm. In adult rat under influence of two modes of normobaric intermittent hypoxic training (IHT): i) softer but prolonged one induced by breathing in normobaric chamber with 11% O2 gas mixture, 15 minuets sessions with 15 minuets rest intervals, 5 times daily (first mode) and ii) more severe but shorter one induced by breathing with 8% O2 gas mixture (second mode) were used. The intensity of lipid peroxidation and antioxidant defense mechanisms in rat organism were estimated before and after IHT by measuring malon dialdehyde (MDA) content and enzymatic activity of superoxide dismutase (SOD) and catalase (CAT) in the blood and the liver. It has been shown that IHT in the first mode didn't essentially influence both on PAO induced, cyclosporin A--sensitive mitochondrial swelling and indexes of lipid peroxidation as well as the SOD and CAT enzymatic activity. It was established that IHT in the second mode caused pronounced increase in MDA content both in the blood and the liver by 67% and 32% respectively; considerable augmentation of SOD activity in this tissues (by 49% and 32% respectively) and CAT activity (by 18% and 43% respectively). Moreover, in forty five days the activity of SOD exceeded its initial level in three times in both the blood and the liver. It has been established that IHT in the second mode provoke to twice decrease in PAO-induced mitochondrial swelling as compared with mitochondria of the control group, and even in forty five days after IHT stopping the protective effect on mitochondrial PTP opening was well-preserved. These effects were completely abolished in the presence of an inhibitor--cyclosporin A (10(-5) mol/l) that demonstrated mitochondrial swelling to be due to the mitochondrial PTP opening. Our experiments showed that the influence of IHT in more severe mode decreased the sensitivity of mitochondria to the PAO in rat heart mitochondria. Thus resistance of the mitochondrial membrane to an inductor of PTP opening--PAO increase under the influence of IHT in the second mode.
High Alt Med Biol. 2005 Fall;6(3):215-25.
Povea C, Schmitt L, Brugniaux J, Nicolet G, Richalet JP, Fouillot JP.
Universite Paris 13, Faculte de Medecine, Bobigny, France.
Changes in heart rate variability induced by an intermittent exposure to hypoxia were evaluated in athletes unacclimatized to altitude. Twenty national elite athletes trained for 13 days at 1200 m and either lived and slept at 1200 m (live low, train low, LLTL) or between 2500 and 3000 m (live high, train low, LHTL). Subjects were investigated at 1200 m prior to and at the end of the 13-day training camp. Exposure to acute hypoxia (11.5% O(2)) during exercise resulted in a significant decrease in spectral components of heart rate variability in comparison with exercise in normoxia: total power (p < 0.001), low-frequency component. LF (p < 0.001), high-frequency component, HF (p < 0.05). Following acclimatization, the LHTL group increased its LF component (p < 0.01) and LF/HF ratio during exercise in hypoxia after the training period. In parallel, exposure to intermittent hypoxia caused an increased ventilatory response to hypoxia. Acclimatization modified the correlation between the ventilatory response to hypoxia at rest and the difference in total power between normoxia and hypoxia (r (2) = 0.65, p < 0.001). The increase in total power, LF component, and LF/HF ratio suggests that intermittent hypoxic training increased the response of the autonomic nervous system mainly through increased sympathetic activity.
Biol Neonate. 2005;88(4):313-20. Epub 2005 Aug 18.
Boss V, Sola A, Wen TC, Decker MJ.
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. vboss@comcast.net
We previously demonstrated that intermittent hypoxia evokes persistent changes in extracellular striatal dopamine, locomotor activity and executive function, using a rodent model emulating apnea of prematurity in which rat pups are exposed to 20-second bursts of hypoxic gas mix containing 10% oxygen (60 events/h; 6 h/day) from postnatal days 7 to 11. To determine whether subtle repetitive hypoxic insults also induce expression of stress-related genes, we employed real-time RT-PCR to assay gene transcription in neonatal rats subjected to the same paradigm. In addition, we also measured expression of stress-induced transcripts in an age-matched cohort following a more severe oxidative stressor: permanent focal ischemia. Four transcripts were elevated following the ischemic insult: heat shock protein 70 (Hsp70), CL100, nurr77, and heme oxygenase-1. In contrast, these transcripts were not regulated in the majority of neonatal rats exposed to an intermittent hypoxia protocol. Hsp70 was strongly induced, and CL100 and nurr77 were slightly induced in only 2 of 11 post-hypoxic rats compared to controls. These data demonstrate that a single ischemic event elicits expression of specific stress-related genes, whereas 5 days of brief intermittent hypoxic insults typically do not. Thus, it is unlikely that the neurochemical and behavioral morbidity observed in juvenile and adult rodents exposed to intermittent hypoxia during a critical period of brain development are related to stress-induced changes in gene expression.
J Appl Physiol. 2005 Sep;99(3):1006-11.
Chakrabarty K, Fahim M.
Dept. of Physiology, Vallabhbhai Patel Chest Institute, Univ. of Delhi, Delhi-110007, India.
Previous studies have documented that repetitive exposure to intermittent hypoxia, such as that encountered in preparation to high-altitude ascent, influences breathing. However, the impact of intermittent hypoxia on airway smooth muscle has not been explored. Ascents to high altitude, in addition to hypoxia, expose individuals to cold air. The objective of the present study is to examine the effect of chronic intermittent hypobaric hypoxia (CIH) and CIH combined with cold exposure (CIHC) on tracheal smooth muscle responses to various contractile and relaxant agonists. Experiments were performed on tracheal rings harvested from adult guinea pigs exposed either to CIH or CIHC [14 days (6 h/day) at barometric pressure of 350 mmHg with and without cold exposure of 5 degrees C] or to room air (normoxia). CIH and CIHC attenuated maximum contractile responses to ACh compared with normoxia. The maximum contractile response to histamine decreased with CIH, whereas CIHC restored the response back to normoxia. Both CIH and CIHC attenuated maximum contractile responses to 5-HT. Altered contractile responses after CIH and CIHC were independent of epithelium. Isoproterenol-induced relaxation was not altered by CIH, whereas it was enhanced after CIHC, and these responses were independent of the epithelium. The data demonstrate that intermittent exposure to hypoxia profoundly influences contractile response of tracheal smooth muscle, and cold exposure can further modulate the response, implying the importance of cold at high altitude.
Brain Res. 2005 Sep 7;1055(1-2):1-6.
Zhu LL, Zhao T, Li HS, Zhao H, Wu LY, Ding AS, Fan WH, Fan M.
Department of Brain Protection and Plasticity, Institute of Basic Medical Science, Beijing 100850, China.
Intermittent hypoxia has been found to prevent brain injury and to have a protective role in the CNS. To address the possible causes of this phenomenon, we made investigative effort to find out whether intermittent hypoxia affects neurogenesis in the adult rat brain by examining the newly divided cells in the subventricular zone (SVZ) and dentate gyrus (DG). The adult rats were treated with 3000 and 5000 m high altitude 4 h per day for 2 weeks consecutively. 5-Bromo-2-deoxyuridine-5-monophosphate (BrdU) immunocytochemistry demonstrated that the BrdU-labeled cells in the SVZ and DG increased after 3000 and 5000 m intermittent hypoxia. The number of BrdU-labeled cells in the SVZ returned to normal level 4 weeks following intermittent hypoxia. However, the BrdU-labeled cells in the DG had a twofold increase 4 weeks subsequent to intermittent hypoxia. From these data, we conclude that intermittent hypoxia facilitates the proliferation of neural stem cells in situ, and that the newly divided cells in the SVZ and DG react differently to hypoxia. We are convinced by these findings that the proliferation of neural stem cells in SVZ and DG may contribute to adaptive changes following intermittent hypoxia.
J Sci Med Sport. 2005 Jun;8(2):222-32.
Kinsman TA, Gore CJ, Hahn AG, Hopkins WG, Hawley JA, McKenna MJ, Clark SA, Aughey RJ, Townsend NE, Chow CM.
Department of Physiology, Australian Institute of Sport Canberra, Australia.
A popular method to attempt to enhance performance is for athletes to sleep at natural or simulated moderate altitude (SMA) when training daily near sea level. Based on our previous observation of periodic breathing in athletes sleeping at SMA, we hypothesised that athletes' sleep quality would also suffer with hypoxia. Using two typical protocols of nocturnal SMA (2650 m), we examined the effect on the sleep physiology of 14 male endurance-trained athletes. The selected protocols were Consecutive (15 successive exposure nights) and Intermittent (3x 5 successive exposure nights, interspersed with 2 normoxic nights) and athletes were randomly assigned to follow either one. We monitored sleep for two successive nights under baseline conditions (B; normoxia, 600 m) and then at weekly intervals (nights 1, 8 and 15 (N1, N8 and N15, respectively)) of the protocols. Since there was no significant difference in response between the protocols being followed (based on n=7, for each group) we are unable to support a preference for either one, although the likelihood of a Type II error must be acknowledged. For all athletes (n=14), respiratory disturbance and arousal responses between B and N1, although large in magnitude, were highly individual and not statistically significant. However, SpO2 decreased at N1 versus B (p<0.001) and remained lower on N8 (p<0.001) and N15 (p<0.001), not returning to baseline level. Compared to B, arousals were more frequent on N8 (p=0.02) and N15 (p=0.01). The percent of rapid eye movement sleep (REM) increased from N1 to N8 (p=0.03) and N15 (p=0.01). Overall, sleeping at 2650 m causes sleep disturbance in susceptible athletes, yet there was some improvement in REM sleep over the study duration.
J Neurobiol. 2005 Oct;65(1):72-84.
Zhang JX, Chen XQ, Du JZ, Chen QM, Zhu CY.
Division of Neurobiology and Physiology, College of Life Sciences, Yuquan Campus,Zhejiang University, Hangzhou, 310027, China.
Hypoxia has generally been reported to impair learning and memory. Here we established a hypoxia-enhanced model. Intermittent hypoxia (IH) was simulated at 2 km (16.0% O2) or 5 km (10.8% O2) in a hypobaric chamber for 4 h/day from birth to 1, 2, 3, or 4 week(s), respectively. Spatial learning and memory ability was tested in the Morris water maze (MWM) task at ages of postnatal day 36 (P36)-P40 and P85-89, respectively, and in the 8-arm maze task at P60-68. The long-term potentiation (LTP), synaptic density, and phosphorylated cAMP-responsive element-binding protein (p-CREB) level in the hippocampus were measured in mice at P36 under the IH for 4 weeks (IH-4w). The results showed that IH for 3 weeks (IH-3w) and IH-4w at 2 km significantly reduced the escape latencies of mice at P36-40 in the MWM task with significantly enhanced retention, and this spatial enhancement was further confirmed by the 8-arm maze test in mice at P60-68. The improvement in MWM induced by IH-4w at 2 km was still maintained in mice at P85-89. IH-4w at 2 or 5 km significantly increased amplitude of LTP, the number of synapse, and the p-CREB level in the hippocampus of P36 mice. These results indicated that IH (4 h/day) exposure to neonatal mice at 2 km for 3 or 4 weeks enhanced mice spatial learning and memory, which was related to the increased p-CREB, LTP, and synapses of hippocampus in this model. Copyright (c) 2005 Wiley Periodicals, Inc.
Int J Cardiol. 2005 Jul 8; [Epub ahead of print]
Lee SD, Kuo WW, Wu CH, Lin YM, Lin JA, Lu MC, Yang AL, Liu JY, Wang SG, Liu CJ, Chen LM, Huang CY.
School of Physical Therapy, Chung-Shan Medical University, Taichung, Taiwan, ROC.
BACKGROUND: Controversial effects of intermittent hypobaric hypoxia such as cardiac damage or cardiac protection are still mysterious. It is unclear if short-term and long-term intermittent hypobaric hypoxic challenges exert different effects on cytochrome c oxidase and Bcl-2 family in rat heart. METHODS: Sixty Sprague-Dawley rats were randomized assigned into two groups: first, short-term intermittent hypobaric hypoxia (STIHH)-normobaric normoxia (n=10), hypobaric hypoxia (380 mmHg, 12% O(2), 8 hr/day) for 1 day (n=10), and for 4 days (n=10) and second, long-term intermittent hypobaric hypoxia (LTIHH)-normobaric normoxia (n=10), hypobaric hypoxia for 1 week (n=10) and 2 weeks (n=10). After STIHH or LTIHH challenge, myocardial morphology, cytochrome c oxidase and pro-apoptotic Bcl-2 family in the excised left ventricle were determined by histological analysis, Western blotting, and RT-PCR. RESULTS: Increased wall thickness and abnormal myocardial architecture were observed after LTIHH. Cytochrome c oxidase and anti-apoptotic Bcl-2 protein were significantly increased after STIHH, but were decreased after LTIHH. Pro-apoptotic BNIP3 and Bad proteins were significantly decreased after STIHH but increased after LTIHH. CONCLUSIONS: STIHH appeared to exert protective effects on hearts whereas LTIHH appeared to exert deleterious effects, which imply that deleterious or advantageous effect of cardiac adaptation after intermittent hypobaric hypoxia is tightly time-course dependent.
[Article in Ukrainian]
Radziievs'kyi PO.
Boris Grinchenko Kyiv Municipal Pedagogical University.
Normobaric intermittent hypoxic training (IHT) is an effective method for improvement of the FRS state, increase of the aerobic productivity, as well as general and special capacity for work in sportsmen of high qualification. High efficacy of IHT in improving all aspects of sportsmen FRS is a result of alternating the hypoxic influences and normoxic intervals between them during which the level of plastic processes remains increased, oxygen tension in arterial blood and tissues increases to nonnoxic values. After IHT course, the state of organ respiration improves, the respiration volume, a part of alveolar ventilation in the minute volume of respiration, oxygen saturation of arterial blood, hemoglobin content in blood--increase as well as economy and efficacy of oxygen regimes of organism, general and special (especially important) physical capacity for work.
Scand J Med Sci Sports. 2005 Jun;15(3):182-7.
Lundby C, Nielsen TK, Dela F, Damsgaard R.
The Copenhagen Muscle Research Centre, Rigshospitalet, Blegdamsvej, Copenhagen O, Denmark. Carsten@CMRC.dk
This study was performed to investigate the effects of intermittent hypoxic exposure on blood and exercise parameters. Eight sea level residents were exposed to 2 h daily stimulus to 4100 m altitude in a hypobaric chamber for a total of 14 days. Exercise performance was evaluated at sea level before and after the hypoxic stimulation. Blood samples were obtained before, during, and at time points up to 14 days after the hypoxic exposure. No changes were observed in haemoglobin, haematocrit, reticulocytes, serum transferrin receptors, or EPO levels in the blood. Submaximal cycle (150 W) ergometer exercise corresponded to a oxygen uptake of 1.9+/-0.1 and 1.9+/-0.1 L min(-1) before and after the intermittent altitude exposure, respectively. At maximal exercise the workloads attained were 343+/-17 and 354+/-27 W before and after the exposure, with corresponding oxygen uptakes of 4.0+/-0.2 and 4.2+/-0.2 L min(-1). It is concluded that intermittent hypoxic exposure to 4100 m altitude for 2 h daily and a total of 14 days does not affect exercise capacity.
J Appl Physiol. 2005 Sep;99(3):1064-9. Epub 2005 May 5.
Beguin PC, Joyeux-Faure M, Godin-Ribuot D, Levy P, Ribuot C.
Laboratoire HP2, Hypoxie Physiopathologie Respiratoire et Cardiovasculaire, EA3745, ESPRI INSERM, Faculte de Medecine-Pharmacie, Universite Grenoble I, Domaine de la Merci, 38706 La Tronche Cedex, France.
In this study, we investigated the influence of depth and duration of intermittent hypoxia (IH) on the infarct size development in isolated rat heart. The role of nitric oxide synthase (NOS) and ATP-sensitive K+ (K(ATP)) channel was also studied. Wistar male rats were exposed to IH [repetitive cycles of 1 min, 40 s with inspired oxygen fraction (FI(O2)), 5 or 10%, followed by 20-s normoxia], during 30 min or 4 h. Another group was exposed to 4 h of continuous hypoxia with 10% FI(O2). Twenty-four hours later, their hearts were isolated and subjected to a 30-min no-flow global ischemia-120-min reperfusion sequence. For some hearts, N(omega)-nitro-L-arginine methyl ester (L-NAME) (a nonselective inhibitor of NOS) or 5-hydroxydecanoic acid (5-HD) (a selective mitochondrial K(ATP) blocker) was infused before ischemia. Infarct size (in percentage of ventricles) was significantly reduced by prior IH for 4 h (10% FI(O2)) (21.8 +/- 3.1 vs. 33.5 +/- 2.5% in sham group). This effect was abolished by L-NAME or 5-HD. Infarct size was not different in groups subjected to either 30 min of IH or to continuous hypoxia compared with sham group. In contrast, IH for 4 h (5% FI(O2)) significantly increased infarct size (45.1 +/- 3.6 vs. 33.5 +/- 2.5% in sham group). Acute IH for 4 h with a minimal FI(O2) of 10% induced a delayed preconditioning against myocardial infarction in the rat, which was abolished by NOS inhibition and mitochondrial K(ATP) channel blockade. Depth, duration, and intermittence of hypoxia appeared to be critical for cardioprotection to occur.
Can J Appl Physiol. 2005 Feb;30(1):61-73.
Villa JG, Lucia A, Marroyo JA, Avila C, Jimenez F, Garcia-Lopez J, Earnest CP, Cordova A.
Dept. of Physical Education, Univ. of Leon, Leon, Spain.
In this study we examined the effects of intermittent hypoxia exposure (IHE) in a group of professional cyclists (n = 6; age 26 +/- 1 yr) competing in the 2001 Vuelta a Espana. After each daily stage, treated subjects received four 5-min bouts of normobaric IHE (mean O2 concentration of 12.6%, simulating a mean altitude of 4,000 m) interspersed with 5-min bouts of breathing hotel room air (normoxia) until completing a total IHE of 20-min duration. The primary outcome, compared to a control group of similar characteristics not receiving IHE (n = 5; age 25 +/- 1 yr), was the % increase in erythropoietin (Epo) from the beginning to the end of the Vuelta. Statistical analysis showed that Epo increase tended to be higher (p = 0.052) in the IHE group than in controls (37.4 +/- 5.8% vs. -4.4 +/- 19.5%, respectively). However IHE had no effect on reticulocytes or erythrocyte count (p > 0.05).
Clin Exp Pharmacol Physiol. 2005 May-Jun;32(5-6):447-9.
Prabhakar NR, Peng YJ, Jacono FJ, Kumar GK, Dick TE.
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. nrp@po.cwru.edu
1. Humans experiencing intermittent hypoxia (IH) owing to recurrent apnoea syndromes exhibit serious cardiovascular morbidity, including high blood pressure, increased sympathetic nerve activity, cardiac arrhythmia and myocardial infarction. Although apnoeas are accompanied by a simultaneous decrease in arterial O(2) (hypoxia) and an increase in CO(2) (hypercapnia), studies on experimental animals suggest that hypoxia, rather than hypercapnia, is the primary stimulus for developing hypertension and enhanced sympathetic nerve activity. Enhanced hypoxic-sensing ability of the carotid bodies and the ensuing reflex activation of the sympathetic nervous system have been suggested to play a critical role in cardiorespiratory alterations resulting from recurrent apnoeas. 2. The purpose of the present review is to highlight recent studies demonstrating the effects of IH on carotid body sensory activity and its consequences on sympathetic activation in a rodent model of chronic IH. Adult rats exposed to chronic IH (15 s of 5% O(2) followed by 5 min of 21% O(2), nine episodes per h, 8 h/day for 10 days) exhibited selective enhancement of carotid body sensory response to hypoxia. In addition, chronic IH induced a novel form of sensory plasticity in the carotid body, manifested as sensory long-term facilitation (LTF). Functional changes in the carotid body occurred in the absence of morphological changes in the chemoreceptor tissue. 3. Acute hypoxia increased expiratory modulated splanchnic nerve activity (SNA) and acute IH-induced LTF in SNA. Hypoxia-induced SNA activation was prevented by bilateral sectioning of the sinus nerves. Rats exposed to chronic IH exhibited enhanced hypoxia-induced sympathetic activation and augmented LTF of the SNA. Bilateral sectioning of the sinus nerves abolished these responses, suggesting chronic IH-induced alterations in carotid body sensitivity contribute to LTF in SNA and the subsequent cardiovascular alterations.
High Alt Med Biol. 2005 Spring;6(1):50-9.
Katayama K, Fujita H, Sato K, Ishida K, Iwasaki K, Miyamura M.
Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan. katayama@htc.nagoya-u.ac.jp
The purpose of this study was to elucidate the magnitude and the time course of ventilatory changes resulting from a repeated series of hypoxic exposures. Eight healthy males participated in the present study. The subjects spent 1 h/day in normobaric hypoxia (12% inspired oxygen). Inspired minute ventilation (V(I)), end-tidal partial pressure of carbon dioxide (P(ET(CO2))), and arterial oxygen saturation (SaO2) were measured in a hypoxic tent. These measurements were taken for 10 consecutive days (series 1), and were taken again after the subjects had been away from hypoxic exposure for 1 month (series 2). P(ET(CO2)) decreased and SaO2 increased progressively in the hypoxic tent during the 10 days of intermittent hypoxia in series 1. At the onset of series 2 (days 1 to 3), P(ET(CO2)) was significantly lower and SaO2 was significantly higher than those on day 1 during series 1. These results suggest that humans who have had previous hypoxic exposure adapt sooner to hypoxic condition due to an increase in the magnitude of hyperventilation in the first few days of a series of reexposures to hypoxia.
Respir Physiol Neurobiol. 2005 Mar;146(1):55-65.
Katayama K, Sato K, Matsuo H, Hotta N, Sun Z, Ishida K, Iwasaki K, Miyamura M.
Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya 464-8601, Japan. katayama@htc.nagoya-u.ac.jp
The purpose of this study was to clarify the changes in hypercapnic and hypoxic ventilatory responses (HCVR and HVR) after intermittent hypoxia and following the cessation of hypoxic exposure. Twenty-nine males were assigned to one of four groups, i.e., a hypoxic (EX1-H, n=7) or a control (EX1-C, n=7) group in Experiment 1, and a hypoxic (EX2-H, n=8) or a control (EX2-C, n=7) group in Experiment 2. In each experiment, the hypoxic tent system was utilized for intermittent hypoxia, and the oxygen levels in the tent were maintained at 12.3+/-0.2%. In Experiment 1, the EX1-H group spent 3 h/day in the hypoxic tent for 1 week. HCVR and HVR were determined before and after 1 week of intermittent hypoxia, and again 1 and 2 week after the cessation of hypoxic exposure. In Experiment 2, the subjects in the EX2-H group performed 3 h/day for 2 weeks in intermittent hypoxia. HCVR and HVR tests were carried out before and after intermittent hypoxia, and were repeated again after 2 weeks of the cessation of hypoxic exposure. The slope of the HCVR in the EX1-H group did not show a significant increase after 1 week of intermittent hypoxia, while HCVR in the EX2-H group increased significantly after 2 weeks of intermittent hypoxia. The HCVR intercept was unchanged following 1 or 2 weeks of intermittent hypoxia. There was a significant increase in the slope of the HVR after 1 and 2 weeks of intermittent hypoxia. The increased HCVR and HVR returned to pre-hypoxic levels after 2 weeks of the cessation of hypoxia. These results suggest that 3 h/day for 2 weeks of intermittent hypoxia leads to an increase in central hypercapnic ventilatory chemosensitivity, which is not accompanied by a re-setting of the central chemoreceptors, and that the increased hypercapnic and hypoxic chemosensitivities are restored within 2 weeks after the cessation of hypoxia.
[Article in Ukrainian]
Havenauskas BL, Man'kovs'ka IM, Nosar VI, Nazarenko AI, Bratus' LV.
The aim of this study was to investigate physical endurance, maximal oxygen uptake, oxygen partial pressure, and pH in blood and skeletal muscle as well as the muscle metabolic parameters (lactate and pyruvate concentration, lactate/pyruvate and NAD/NADH ratios, succinate dehydrogenase activity, ADP-stimulated mitochondrial respiration) under various regimen of combination of endurance training with intermittent hypoxic training (IHT) in adult Wistar rats. It was shown that physical endurance, maximal oxygen uptake, and muscle PO2 (PmO2) were maximally increased in those animals who simultaneously underwent endurance training and IHT. The same animals demonstrated the minimal decrease in PmO2, blood and muscle pH under testing intensive physical workload. The latter led to the lesser shifts in metabolic parameters in the muscle of rats adapted both to IHT and endurance training than in rats adapted to endurance training only. The combined effects of IHT and adaptation to load hypoxia resulted in an increase of the role of NADH - oxidation pathway in the mitochondrial energy production.
Respir Physiol Neurobiol. 2005 Jan 15;145(1):33-9.
Koehle MS, Foster GE, McKenzie DC, Sheel AW.
Department of Family Medicine, Allan McGavin Sport Medicine Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
Measurement of hypoxic ventilatory response (HVR) involves an exposure to hypoxia which, if repeated over several days might act as an intermittent hypoxic stimulus. The purpose of this study was to measure HVR repeatedly over 5 days to determine whether it was affected by repeated measurement. Nine healthy male subjects completed an isocapnic HVR test, on one occasion, followed 5 days later by one measurement each day for 5 days. Each test lasted approximately 5-8 min with inspired oxygen concentration declining to as a low as 5-6%. No systematic trend was observed in HVR over the 5-day period (p>0.05). There were no significant differences in HVR between any of the test days. Regression failed to show any trend in HVR over the five sequential days. The calculated mean coefficient of variation for HVR for each subject was 27%. There is no evidence that the short exposure to hypoxia as part of HVR measurement is a co-intervention when measured repeatedly over 5 days in physiological studies.
Med Sci Sports Exerc. 2005 Jan;37(1):138-46.
Roels B, Millet GP, Marcoux CJ, Coste O, Bentley DJ, Candau RB.
UPRES EA 3759 Faculty of Sport Sciences, 700 avenue Pic St Loup, 34090 Montpellier, France. belle.roels@univ-montpl.fr
PURPOSE: The aim of this study was to test the hypothesis that intermittent hypoxic interval training improves sea level cycling performance more than equivalent training in hypoxia or normoxia. METHODS: Thirty-three well-trained cyclists and triathletes (25.9 +/- 2.7 yr, VO(2max) 66.1 +/- 6.1 mL.min(-1).kg(-1)) were divided into three groups: intermittent hypoxic (IHT, N = 11, P(I)O(2) of 100 mm Hg), intermittent hypoxic interval training (IHIT, N = 11) and normoxia (Nor, N = 11, P(I)O(2) of 160 mm Hg) and completed a 7-wk training program, consisting of two high-intensity (100 or 90% relative peak power output) interval training sessions each week. Each interval training session was performed in a laboratory on the subject's own bicycle, in normoxic or hypoxic conditions for the Nor and the IHT group, respectively. The IHIT group performed warm-up and cool-down plus recovery from each interval in hypoxic conditions. In contrast to IHT, interval exercise bouts were performed in normoxic conditions. RESULTS: Mean power output during a 10-min cycle time trial improved after the first 4 wk of training by 5.2 +/- 3.9, 3.7 +/- 5.9, and 5.0 +/- 3.4% for IHIT, IHT, and Nor, respectively, without significant differences between groups. Moreover, mean power output did not show any significant improvement in the following 3 wk in any group. VO(2max) (L.min(-1)) increased only in IHIT during the training period (8.7 +/- 9.1%; P < 0.05). No changes in cycling efficiency or in hematological variables (P > 0.05) were observed. CONCLUSION: Four weeks of interval training induced an improvement in endurance performance. However, short-term exposure to hypoxia (approximately 114 min.wk(-1)) did not elicit a greater increase in performance or any hematological modifications.