Haematological acclimation and re-acclimation to hypoxia in the mouse

Haematological responses throughout 4 w of initial acclimation (IA) and three paradigms of re-acclimation (RA) to hypoxia (FI_O2=0.12${\text{FI}}_{{\text{O}}_2}=0.12$) were examined in female mice. We hypothesised that (i) haematological responses would be increased during re-exposure, resulting in greater O₂-carrying capacity in RA compared to IA; and (ii) further improvements would occur when abbreviating the de-acclimation period to 1 w (RA_↓DA) or extending the IA period to 8 w (RA_↑IA). The serum [EPO] response was blunted in all RA groups compared to IA but the resulting reticulocyte response was similar in all experimental groups. The [Hb] response was the same in RA and RA_↓DA as in IA but was blunted in RA_↑IA due to a reduction in mean corpuscular Hb. The sensitivity of EPO-producing cells appears blunted but the sensitivity of erythroid precursors to EPO is enhanced by recent hypoxic exposure. Erythropoietic regulation is altered during RA in a manner that is dependent on the paradigm of initial exposure.     

Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study

The aim of the study was to examine the efficacy and safety of temazepam on nocturnal oxygenation and next-day performance at altitude. A double-blind, randomized, cross-over trial was performed in Thirty-three healthy volunteers. Volunteers took 10 mg of temazepam and placebo in random order on two successive nights soon after arrival at 5000 m, following a 17-day trek from 410 m. Overnight SaO(2) and body movements, and next-day reaction time, maintenance of wakefulness and cognition were assessed. Compared with placebo, temazepam resulted in a reduction in periodic breathing from a median (range) of 16 (0-81.3)% of the night to 9.4 (0-79.6)% (P = 0.016, Wilcoxon's signed-rank test), associated with a small but significant decrease in mean nocturnal SaO(2) from 78 (65-84)% to 76 (64-83)% (P = 0.013). There was no change in sleep latency (P = 0.40) or restlessness (P = 0.30). Temazepam had no adverse effect on next-day reaction time [241 (201-380) ms postplacebo and 242 (204-386) ms post-temazepam], maintenance of wakefulness (seven trekkers failed to maintain 40 min of wakefulness postplacebo, and four post-temazepam), cognition or acute mountain sickness. At high altitude temazepam reduces periodic breathing during sleep without an adverse effect on next-day reaction time, maintenance of wakefulness or cognition. The 2% reduction in mean SaO(2) post-temazepam is likely to be predominantly because of acclimatization, as by chance more trekkers took temazepam on the first night (19 versus 14). We conclude that at high altitude temazepam is effective in reducing periodic breathing, and is safe to use, without any adverse effect upon next-day performance.     

Long-term exposure to intermittent hypoxia results in increased hemoglobin mass,reduced plasma volume,and elevated erythropoietin plasma levels in man

While it is well established that highlanders have optimized their oxygen transport system, little is known about the acclimatization of those who move between different altitudes. The purpose of this study was to establish whether the acclimatization to long-term intermittent hypoxic exposure in members of the Chilean Army who frequently move from sea level to 3,550 m altitude is correlated with acute acclimatization or chronic adaptation to hypoxia. A group of officers was exposed intermittently to hypoxia for about 22 years (OI, officers at intermittent hypoxia) and a group of soldiers for 6 months (SI, soldiers at intermittent hypoxia). Both groups were compared to residents at altitude (RA) and to soldiers at sea level (SL). When compared to SL, we observed an 11% increase in total hemoglobin mass (tHb) as well as a corresponding increase in red cell volume (RCV), hemoglobin concentration and hematocrit in all three groups at altitude. Plasma volume (PV) and blood volume (BV) decreased at altitude but increased when OI and SI returned to sea level. Moreover, intermittent hypoxic exposure of OI and SI resulted in increased plasma erythropoietin (Epo) levels, which peaked on day 2 at high altitude followed by decreasing levels during the successive days, and reaching pre-altitude values in SI even when staying at altitude. In conclusion, with regard to tHb and RCV, the acclimatization to long-term intermittent hypoxia resembles the adaptation to chronic hypoxia, while PV and BV regulation mimicked acclimatization to acute hypoxia. Remarkably, finely controlled regulation of Epo expression still occurs after up to 22 years of weekly exposure to altitude. Electronic Publication     

Regional cerebral blood flow during acute hypoxia in individuals susceptible to acute mountain sickness

Individuals susceptible to high altitude pulmonary edema show altered pulmonary vascular responses within minutes of exposure to hypoxia. We hypothesized that a similar acute-phase vulnerability to hypoxia may exist in the brain of individuals susceptible to acute mountain sickness (AMS). In established AMS and high altitude cerebral edema, there is a propensity for vasogenic white matter edema. We therefore hypothesized that increased cerebral blood flow (CBF) during acute hypoxia would also be disproportionately greater in white matter (WM) than grey matter (GM) in AMS-susceptible subjects. We quantified regional CBF using arterial spin labeling MRI during 30 min hypoxia (F(I)O(2) = 0.125) in two groups: AMS-susceptible (AMS-S, n = 6) who invariably experienced AMS at altitude, and AMS-resistant (AMS-R, n = 6) who never experienced AMS despite multiple rapid ascents to high altitude. SaO(2) during hypoxia did not differ between groups (AMS-S = 87+/-4%, AMS-R = 89+/-3%, p = 0.3). Steady-state whole-brain CBF increased in hypoxia (p<0.005), but did not differ between groups (normoxia: AMS-S = 42.7+/-14.0 ml/(100 g min), AMS-R = 41.7+/-10.1 ml/(100 g min); hypoxia: AMS-S = 47.8+/-19.5 ml/(100 g min), AMS-R = 48.2+/-10.1 ml/(100 g min), p = 0.65), and cerebral oxygen delivery remained constant. The percent change in CBF did not differ between brain regions or between groups (although absolute CBF change was greater in GM): (GM: AMS-S = 6.1+/-7.7 ml/(100 g min) (10+/-11%), AMS-R = 8.3+/-5.7 ml/(100 g min) (17+/-11%), p = 0.57; WM: AMS-S = 4.3+/-5.1 ml/(100 g min) (12+/-15%), AMS-R = 4.8+/-2.9 ml/(100 g min) (16+/-9%), p = 0.82). CONCLUSION: CBF increases in acute hypoxia, but is not different between WM and GM, irrespective of AMS susceptibility. Acute phase differences in regional CBF during acute hypoxia are not a primary feature of susceptibility to AMS.     

Exhaled nitric oxide is reduced upon chronic intermittent hypoxia exposure in well-acclimatized mine workers

The aim of this study was to assess how exhaled nitric oxide (NO) levels in healthy subjects changed upon exposure to intermittent hypoxia at high altitude. Eighty-one healthy subjects with a mean age of 31.8±6.7 years, well acclimatized at altitudes of 3800-4000m above sea level, and employed by a gold-mining company were recruited for the study. Baseline, altitude-corrected partial exhaled NO levels (PE(NO)) were measured in Bishkek, Kyrgyzstan (780m). Measurements were then taken on day 1 of the ascent to the mine, which is located at an altitude of 4000m, on day 3 and finally at the end of the 2- or 3-week shifts. The mean PE(NO) level was 9.49±3.66nmHg in Bishkek and was lower in females than in males (9.76±3.58nmHg vs. 7.03±3.71nmHg). When compared to the first day at altitude, exhaled NO was reduced by 17.2% on day 3 (p=0.001) and 29.6% by the end of the shift (p<0.001). In summary, this study of well-acclimatized high-altitude miners demonstrates that despite the absence of clinical signs of desadaptation, there is an apparent reduction in exhaled NO.     

Gammadelta lymphocyte response to porcine reproductive and respiratory syndrome virus

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be one of the most important diseases facing swine industry today. Following PRRSV infection pigs develop both humoral and cell-mediated responses following PRRSV exposure; however, the relative importance in protection and clearance of the virus is not yet completely understood. Swine contain a large percentage of gammadelta T-lymphocytes in peripheral circulation capable of responding to various pathogens in both an innate and specific immune response. The objectives of this study were to determine whether gammadelta lymphocytes functionally respond to PRRSV upon initial exposure and re-exposure. Four month old PRRSV free gilts were intranasally inoculated with a field isolate MN-30100 then assessed at various time points post infection. On day 120, pigs were re-exposed with MN-30100 PRRSV strain and subsequently were bled on days 0, 7, and 14 post re-exposure. Lymphocyte subpopulations, antigen specific proliferation, and IFN-gamma production were evaluated throughout the study. Circulating gammadelta lymphocytes in PRRSV exposed animals expanded between days 14 to 70 (d14-d70, p = 0.016); following antigen stimulation, gammadelta lymphocyte proliferated by day 14 (d0-d14, p = 0.001) continuing through day 60. gammadelta lymphocytes produced IFN-gamma by day 14 pi continuing through day 50 (d0-d50, p = 0.004). Following re-exposure both gammadelta+ and CD4+ lymphocytes increased in IFN-gamma production. These results are not fully conclusive on the role of gammadelta lymphocytes against PRRSV; the data indicate that gammadelta lymphocytes specifically respond to PRRSV.     

Sleep structure and periodic breathing in Tibetans and Han at simulated altitude of 5000 m

Tibetans are the oldest population living permanently at high altitude. They possess several adaptations to low oxygen pressure that improve oxygen transport. We hypothesised that native Tibetans have mechanisms allowing them to maintain a better sleep structure and oxygenation during sleep at high altitude than newcomers from lower altitudes acclimatised to living at high altitude. We studied eight healthy young Tibetans, aged 26+/-7 years, and six healthy young Han aged 30.5+/-4 years. All subjects were living on the Tibetan plateau at an altitude of around 4000 m. Investigations were performed in Xining at an altitude of 2261 m, PB=581 mmHg. Two full polysomnographies (PSG) were performed in a hypobaric chamber, one at the ambient altitude, the second during acute exposure to the simulated altitude of 5000 m (PB=405 mmHg). Both PSG were done on the same night using split night design. At 2261 m no differences in sleep structure, breathing pattern during sleep or oxygenation were found, except a higher number of arousals and awakenings in Han (P<0.002). At 5000 m Tibetans had a longer sleep time (P=0.002), shorter stage 1 non-REM sleep (P<0.001) and longer stage 2 non-REM sleep than Han (P<0.001). Tibetans showed a trend to have more periodic breathing (PB) and higher mean arterial blood saturation than Han (NS). Our data suggest that Tibetans preserved better sleep structure and arterial blood oxygenation than Han during acute exposure to the simulated altitude of 5000 m.     

Intracoronary adiponectin at reperfusion reduces infarct size in a porcine myocardial infarction model

Reperfusion injury (RI) remains an important limitation of myocardial revascularization. The aim of the present study was to evaluate the influence of the intracoronary injection of adiponectin on RI and cardiomyocyte death in a porcine myocardial infarction model. Acute infarction in 14 Polish domestic pigs was induced by inflation of an over the wire balloon (OTW) catheter in the medial left anterior descending artery for 60?min. The study group consisted of 7 pigs in which intracoronary adiponectin (50?μg) was infused through the OTW catheter immediately before reperfusion. The control group (n=7) was administered placebo. Animals were sacrificed after two days of follow-up. The infarct area (IA) was stained with tetrazoline and the area at risk (AAR) with intracoronary administration of Evans Blue dye before euthanasia. Hearts in each group had similar AARs (46.2±9.9% vs. 48.4±6.2% of the whole myocardium, p=ns). The IA/AAR% and IA were smaller in the study group when compared to the control (24.7±4.0% vs. 45.3±22.5%, p=0.005; and 11.7±4.9% vs. 20.5±5.6%, p=0.01, respectively). These outcomes corresponded well with the peak troponin levels after 12?h (109.9±60.9 ng/ml vs. 185.5±39.4 ng/ml, p=0.017). After two days there was a significantly higher LVEF in the study group (51.4±8.5% vs. 33.9±8.6%, p=0.002). There was also a trend toward lower apoptosis enhancement in the viable myocardium in the study group (3.11±2.3 vs. 8.92±6.3; p=0.07). The administration of adiponectin into the infarct- related artery is safe and feasible. The treatment significantly reduced the infarct size.     

Effects of a 12-day “live high, train low” camp on reticulocyte production and haemoglobin mass in elite female road cyclists

The aim of this study was to document the effect of “living high, training low” on the red blood cell production of elite female cyclists. Six members of the Australian National Women's road cycling squad slept for 12 nights at a simulated altitude of 2650?m in normobaric hypoxia (HIGH), while 6 team-mates slept at an altitude of 600?m (CONTROL). HIGH and CONTROL subjects trained and raced as a group throughout the 70-day study. Baseline levels of reticulocyte parameters sensitive to changes in erythropoeisis were measured 21 days and 1 day prior to sleeping in hypoxia (D1 and D20, respectively). These measures were repeated after 7 nights (D27) and 12 nights (D34) of simulated altitude exposure, and again 15 days (D48) and 33 days (D67) after leaving the altitude house. There was no increase in reticulocyte production, nor any change in reticulocyte parameters in either the HIGH or CONTROL groups. This lack of haematological response was substantiated by total haemoglobin mass measures (CO-rebreathing), which did not change when measured on D1, D20, D34 or D67. We conclude that in elite female road cyclists, 12 nights of exposure to normobaric hypoxia (2650?m) is not sufficient to either stimulate reticulocyte production or increase haemoglobin mass.     

Mite avoidance can reduce air trapping and airway inflammation in allergic asthmatic children

BACKGROUND: We investigated the effects of prolonged allergen avoidance in 18 house dust mite-sensitized asthmatic children during a prolonged residential period at a high altitude, allergen-free environment. METHODS: Evaluations of residual volume (RV) and exhaled nitric oxide (eNO) were performed (i) at admission to the residential house in September, (ii) in December after 3 months of stay, (iii) in January after 15 days at home, exposed to allergens, and (iv) in June after 9 months of stay. RESULTS: During the study period RV showed a significant decrease in December (from 117.5 +/- 7.7% to 96.5 +/- 3.2%) (P < 0.02) and a following increase in January (126.2 +/- 17.2%), after allergen re-exposure (P < 0.03). RV decreased again in June at the end of the study period (91.1 +/- 6.0%) (P = 0.001). FEV(1), FEF(25-75) and VC values did not present significant variations. ENO showed a significant decrease in December after 3 months at high altitude (from 21.3 +/- 3.9 p.p.b. to 11.9 +/- 1.7 p.p.b.) (P = 0.03), but no further significant change. No correlation was found between lung volumes and eNO, probably reflecting different aspects of asthma. CONCLUSIONS: Results suggest that RV may be more sensitive than other respiratory function parameters in identifying children with air trapping, being influenced significantly as the inflammatory indices by effective allergen avoidance/exposure regimen.     

Heat reactions of Bushmen

When Bantu males are exposed to ambient air temperatures of 78, 82, 86 and 90 °F Effective Temperature it is possible to distinguish clearly between unacclimatised, partially acclimatised and highly acclimatised states. A sample of Bushmen was exposed to this range of E. T.'s in a portable climatic chamber. Their rectal temperatures at the end of the third hour of exposure reached 101 °F at 78 ° and 82 °F E.T., 102.2 °F at 86 °F E.T. and 102.5 °F at 90 °F E.T. Sweat rates were highest in the first hour of exposure in all four heat stress conditions. Sweat rates decreased generally throughout the three-hour period, but the rank order of sweat rates were maintained. Sweat rates were plotted against rectal temperatures for each hour and also for the average values of the three hours of exposure. Curves fitted to the Bushmen data lie between the curves fitted to the data of unacclimatised and acclimatised Bantu for each of the three hours. When curves relating the mean sweat rates for the three hours of exposure at each of the E.T. conditions are compared with those for unacclimatised and acclimatised Bantu, it is found that the curve drawn on the Bushmen data again occupy a position midway between the other two curves. These three groups and a group of U. S. students are also compared in this paper in terms of physiological limits based on a steady level of rectal temperature, and based on the percentages of the samples exceeding a rectal temperature of 101 °F and 102.5 °F. The limiting E.T.'s for the Bushmen were found to be similar to those of unacclimatised Bantu and, generally, higher than for the U. S. students.     

Re-exposure to wild-type virus stabilizes measles-specific antibody levels in late convalescent patients.

BACKGROUND: Infection with wild-type (wt) measles virus strains induces high antibody levels believed to provide life-long protection against disease. OBJECTIVES: Humoral immunity was followed up in convalescent measles patients to assess the persistence of specific antibodies after measles disease in individuals without and with documented re-exposure to wt virus. STUDY DESIGN: Paired sera were collected from 43 late convalescents (LC) before re-exposure and 3.7-4.8 years after re-exposure to at least one measles patient (LC+ group). Antibody persistence in this group was compared to paired sera from 43 age- and sex-matched controls without documented exposure to wt virus (LC- group). Paired sera were also obtained from 26 measles patients 1.3-1.7 and 3.8-4.1 years after they had recovered from measles to observe the waning of antibodies in early convalescents (EC group). RESULTS: Antibody levels decreased by 12.1% (CI: 3.2-20.3%, p=0.01) within 6.3 years in the LC- group of late convalescent measles patients. In contrast, in the LC+ group GMT of first and second sera were virtually identical, indicating that exposure to wt virus stabilizes antibody levels even in absence of a detectable secondary immune response. In a subset of late convalescents of group LC+ with a secondary immune response, antibody waning after re-exposure was as high as 15.6%/year (CI: 13.0-17.7%/year), corresponding to a half-life of 4.1 years (CI: 3.5-5.0 years), but antibodies were still higher than before re-exposure. In the EC group GMT decreased by 6.5% (95% CI: -13.3% to +0.1%) during 2.5 years but significance was low (p=0.08). CONCLUSION: The maintenance of antibody levels in convalescent measles patients is at least partially dependant on recurrent exposure to circulating wt virus.     

Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.     

Effects of acetylcholine and GABA on neurons in the area postrema of Suncus murinus brainstem slices

The choroid plexus in adult rats was examined for any structural alteration or apoptotic cell death following a high altitude exposure which leads to the development of hypobaric hypoxia due to reduced oxygen tension in the atmospheric air. Caspase-3 (a protease which mediates apoptosis) immunoreactivity was absent in the choroid plexus epithelial cells in the control rats and following altitude exposure; Bcl-2 (anti-apoptotic protein) and Bax (pro-apoptotic protein) immunoreactivity were upregulated at 3 h-2 days following the altitude exposure when compared to the controls but not in longer surviving rats. At the ultrastructural level, glycogen particles and vacuoles were observed in some epithelial cells at 7 days following the altitude exposure. It is suggested that transient exposure to high altitude may not cause much damage to the choroid plexus epithelial cells except for some structural alteration which may be due to altered metabolism of the cells in response to hypobaric hypoxia.     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Summary Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (–27%) and phospholipids (–19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.Abbreviations VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins     

Branched-chain amino acid supplementation during trekking at high altitude

Summary To investigate the influence of a branched-chain amino acid (BCAA) supplementation on chronic hypoxia-related loss of body mass and muscle loss, 16 subjects [age 35.8 (SD 5.6) years] participating in a 21-day trek at a mean altitude of 3,255 (SD 458) m, were divided in two age-, sex- and fitness-matched groups and took either a dietary supplementation of BCAA (5.76, 2.88 and 2.88 g per day of leucine, isoleucine and valine, respectively) or a placebo (PLAC) in a controlled double-blind manner. Daily energy intake at altitude decreased by 4% in both groups compared with sea level. After altitude exposure both groups showed a significant loss of body mass, 1.7% and 2.8% for BCAA and PLAC, respectively. Fat mass had decreased significantly by 11.7% for BCAA and 10.3% for PLAC, whereas BCAA showed a significantly increased lean mass of 1.5%, as opposed to no change in PLAC. Arm muscle cross-sectional area tended to increase in BCAA, whereas there was a significant decrease of 6.8% in PLAC (P<0.05 between groups). The same tendency, although not significant, was observed for the thigh muscle cross-sectional area. On the whole it seemed that PLAC had been catabolizing whereas BCAA had been synthesizing muscle tissue. Single jump height from a squatted position showed a similar tendency to increase in both groups. Lower limb maximal power decreased less in BCAA than in PLAC (2.4% vs 7.8%, P<0.05). We concluded that BCAA supplementation may prevent muscle loss during chronic hypobaric hypoxia.     

Hypobaric interval hypoxia as a tool for improving tolerance of harmful occupational factors

The method of hypobaric interval hypoxia (HIH) has been developed and approved for application in aerospace, military, prophylactic and rehabilitative medicine. A course of H1H included 10 one-hour daily sessions of hypobaria and interval hypoxia simulating ascent to an altitude from 3 to 5 km a.s.l. Each session comprised a 7 minute exposure to hypoxia (breathing rarified air) alternating with a 3 minute exposure to hyperoxia (breathing oxygen) without a change of the altitude simulated in the low-pressure chamber. The first session included ascent to 3 km, in each of the following sessions (from 2nd to 4th) the altitude was successively increased by 500 m and reached 5 km in sessions 5-10. HIH was shown to be highly efficacious in improving the functional state of the organism and its resistance to unfavourable environmental conditions; also it can be used to correct changes of these parameters.     

Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure

Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure.     

Hypocapnia is associated with increased upper airway expiratory resistance during sleep

We hypothesized that hypocapnia is responsible for increased expiratory resistance during NREM sleep. Hypocapnia was induced by hypoxic hyperventilation in 21 subjects (aged 29.4 ± 7.8 yrs, 10 women, BMI 24.4 ± 4.3 kg/m(2)). Isocapnic hypoxia was induced in 12 subjects of whom, 6 underwent hypocapnic hypoxia in the same night. Upper airway resistance (R(UA)) was measured at the linear pressure-flow relationship during inspiration and expiration. Inspiratory flow limitation (IFL) was defined as the dissociation in pressure-flow relationship. (1) Expiratory R(UA) increased during hypocapnic but not isocapnic hypoxia relative to control (11.0 ± 5.6 vs. 8.2 ± 3.6 cm H(2)O/L/s; p < 0.05, and 11.45.0 vs. 10.94.4 cm H(2)O/L/s; p = NS, respectively). (2) No gender difference was found in R(UA) (p = NS). (3) Increased expiratory R(UA) correlated with the IFL change during hypocapnic but not isocapnic hypoxia. (4) No changes were noted in inspiratory R(UA) or IFL. Expiratory R(UA) increased during hypocapnia and was associated with IFL, indicating upper airway narrowing. Gender does not influence the upper airway response to hypocapnic hypoxia.     

The ‘lactate paradox’, evidence for a transient change in the course of acclimatization to severe hypoxia in lowlanders

The metabolic response to exercise at high altitude is different from that at sea level, depending on the altitude, the rate of ascent and duration of acclimatization. One apparent metabolic difference that was described in the 1930s is the phenomenon referred to as the ‘lactate paradox’. Acute exposure to hypoxia results in higher blood lactate accumulation at submaximal workloads compared with sea level, but peak blood lactate remain the same. Following continued exposure to hypoxia or altitude, blood lactate accumulation at submaximal work and peak blood lactate levels are paradoxically reduced compared with those at sea level. It has recently been shown, however, that, if the exposure to altitude is sufficiently long, blood lactate responses return to those seen at sea level or during acute hypoxia. Thus, to evaluate the ‘lactate paradox’ phenomenon in relation to time spent at altitude, five Danish lowland climbers were studied at sea level, during acute exposure to hypoxia (10% O₂ in N₂) and 1, 4 and 6 weeks after arrival in the basecamp of Mt Everest (～5400 m, Nepal). Basecamp was reached after 10 days of gradual ascent from 2800 m. Peak blood lactate levels were similar at sea level (11.0 ± 0.7 mmol L^?1) and during acute hypoxia (9.9 ± 0.3 mmol L^?1), but fell significantly after 1 week of acclimatization to 5400 m (5.6 ± 0.5 mmol L^?1) as predicted by the ‘lactate paradox’. After 4 weeks of acclimatization, peak lactate accumulation (7.8 ± 1.0 mmol L^?1) was still lower compared with acute hypoxia but higher than that seen after 1 week of acclimatization. After 6 weeks of acclimatization, 2 days after return to basecamp after reaching the summit or south summit of Mt Everest, peak lactate levels (10.4 ± 1.1 mmol L^?1) were similar to those seen during acute hypoxia. Therefore, these results suggest that the ‘lactate paradox’ is a transient metabolic phenomenon that is reversed during a prolonged period of exposure to severe hypoxia of more than 6 weeks.