Cardiac baroreflex control in humans during and immediately after brief exposure to simulated high altitude

To examine the baroreflex response in humans during and immediately after acute hypoxia exposure, the cardiac baroreflex sensitivity (BRS) was studied using adaptation of RR intervals in response to spontaneous systolic blood pressure fluctuations (sequences methodology) in 11 unacclimatized subjects. All measurements were made under fixed breathing rate, and realized consecutively at baseline level (20 min), at an inspired oxygen concentration of 11% (15 min) and again under normoxic conditions (20 min; recovery period). The spontaneous baroreflex response decreases progressively during hypoxic exposure, causing a tachycardic response at this FiO2 without any significant alteration of the systolic or diastolic blood pressure. The magnitude of decrease for this variable at the end of exposure averaged 42.9 +/- 15.6%. The simultaneous spectral analysis of heart rate (HR) variability in hypoxic condition confirmed an alteration in the parasympathetic activity (HFnu: -17.8 +/- 30.9% versus basal conditions, P < 0.01) counterbalanced by an exaggerated sympathetic activity (LFnu: +33 +/- 42.4%, P < 0.05) at the sinus node. Interestingly, we could observe an enhanced cardiac baroreflex response during the period following the inhalation of the hypoxic mixture (+130.6 +/- 15.6% of basal conditions, P < 0.001). There is a relationship with a significant and abrupt increase in the parasympathetic control of HR (mean HR reached 111 +/- 8.1% of the mean basal HR, P < 0.01). These results suggest that brief exposure to hypoxia under rate-controlled ventilation is associated with a significant alteration in the spontaneous cardiac baroreflex. This important cardiac autonomic imbalance is followed by a significant increase in the cardiac parasympathetic drive even after the disappearance of the hypoxic stimulus.     

Intermittent hypoxic training: implications for lipid peroxidation induced by acute normoxic exercise in active men.

Oxidant generation during regular physical exercise training may influence the adaptive responses that have been shown to confer protection against oxidative stress induced by subsequent acute exercise. To examine this, we randomly assigned 32 males to either a normoxic (n=14) or a hypoxic (n=18) group. During the acute phase, subjects in the hypoxic group performed two maximal cycling tests in a randomized double-blind fashion: one under conditions of normoxia and the other under hypoxic conditions (inspired fraction of O(2)=0.21 and 0.16 respectively). During the intermittent phase, the normoxic and hypoxic groups each trained for 4 weeks at the same relative exercise intensity, under conditions of normoxia and hypoxia respectively. During acute exercise under hypoxic conditions, the venous concentrations of lipid hydroperoxides and malondialdehyde were increased, despite a comparatively lower maximal oxygen uptake (VO(2max)) (P<0.05 compared with normoxia). The increases in lipid hydroperoxides and malondialdehyde were correlated with the exercise-induced decrease in arterial haemoglobin oxygen saturation (r=-0.61 and r=-0.50 respectively; P<0.05), but not with VO(2max). Intermittent hypoxic training attenuated the increases in lipid hydroperoxides and malondialdehyde induced by acute normoxic exercise more effectively than did normoxic training, due to a selective mobilization of alpha-tocopherol (P<0.05). The latter was related to enhanced exercise-induced mobilization/oxidation of blood lipids due to a selective increase in VO(2max) (P<0.05 compared with normoxic group). We conclude that lipid peroxidation induced by acute exercise (1) increases during hypoxia; (2) is not regulated exclusively by a mass action effect of VO(2); and (3) is selectively attenuated by regular hypoxic training. Oxidative stress may thus be considered as a biological prerequisite for adaptation to physical stress in humans.     

The BOLD response and vascular reactivity during visual stimulation in the presence of hypoxic hypoxia

A disproportionate increase in cerebral blood flow (CBF) relative to the cerebral metabolic rate of oxygen (CMRO(2)), in response to neuronal activation, results in a decreased oxygen extraction fraction (OEF) and hence local 'hyperoxygenation'. The mismatch is the key 'physiological substrate' for blood oxygenation level dependent (BOLD) fMRI. The mismatch may reflect inefficient O(2) diffusion in the brain tissue, a factor requiring maintenance of a steep [O(2)] gradient between capillary bed and neural cell mitochondria. The aim of this study was to assess vascular responsiveness to reduced blood oxygen saturation, using both BOLD fMRI and the CBV-weighted vascular space occupancy (VASO)-dependent fMRI technique, during visual activation in hypoxic hypoxia. Our fMRI results show decreased amplitude and absence of initial sharp overshoot in the BOLD response, while VASO signal was not influenced by decreasing oxygen saturation down to 0.85. The results suggest that the OEF during visual activation may be different in hypoxia relative to normoxia, due to a more efficient oxygen extraction under compromised oxygen availability. The data also indicate that vascular reactivity to brain activation is not affected by mild hypoxia.     

The haematological and cardiac patterns of adaptation of rabbits to 4,500 m simulated altitude and of readaptation to 400 m

The haemoglobin (Hb), red blood cell count (RBC) and haematocrit (Hct) of 11 male rabbits were measured at weekly intervals during a 5-week exposure period to hypobaric hypoxia (simulated altitude, 4,500 m) and the following 4 weeks after restoring normoxic conditions in a climatic chamber at constant temperature. RBC showed the slowest response, Hct the fastest during adaptation to hypoxia and readaptation to normoxia. The body weight decreased during the 1st week at hypoxia and remained at a reduced level for 2 weeks after the return to normoxia. In female rabbits exposed up to 43 days to hypoxia the heart ventricle quotient (HVQ) (weights of left ventricle + septum/right ventricle) was determined. There was a gradual decrease of HVQ expressing the development of right heart hypertrophy which was not stabilised within the observation period.     

Digitalis toxicity during acute hypoxia in intact conscious dogs.

Intact, conscious dogs were studied under normal and hypobaric conditions to assess the influence of acute hypoxia on the ability of the animals to tolerate ouabain. Animals were made acutely hypoxic by exposure to hypobaric conditions in a chamber maintained at 446 mm Hg. The ability of the dogs to tolerate ouabain was determined by administering intravenously 7.5 mug/kg of the drug as a loading dose followed by infusion at a rate of 3.0 mug/kg/min to an end point consisting of the development of ventricular or atrioventricular junctional tachycardia. Eight dogs, each acting as its own control, were studied under normoxic and acutely hypoxic conditions. During hypoxia, mean arteriol pO2 decreased to 39 plus or minus 1 (S.E.) mm Hg from 80 plus or minus 1 mm Hg at sea level (P less than .001). The cumulative toxic dose of ouabain was modestly but significantly less (P less than .05) during acute hypoxia (71.7 plus or minus 4.3 mug/kg) compared with normoxic (79.2 plus or minus 4.1 mug/kg) conditions. In these experiments a marked hyperventilation response to ouabain was observed just before onset of toxicity which resulted in a pronounced rise in mean arterial pH (normoxia: 7.39 plus or minus 0.01 to 7.72 plus or minus 0.01; hypoxia: 7.48 plus or minus 0.01 to 7.71 plus or minus 0.04) and fall in pCO2 (normoxia: 41 plus or minus 1 to 14 plus or minus 1 mm Hg; hopoxia: 34 plus or minus 1 to 16 plus or minus 2 mm Hg). Ouabain-induced increases in systemic arterial pressure were comparable in normal and acutely hypoxic animals. Thus, acute hypoxia in unanesthetized dogs exposed to hypobaric conditions results in a decrease of only 10% in the ouabain dose required to produce cardiac arrhythmias, and toxic doses of ouabain produce a striking respiratory alkalosis.     

Hypoxia provokes leukotriene-dependent neutrophil sequestration in perfused rabbit hearts

Isolated rabbit hearts were perfused with salt solution containing autologous 111In-labeled neutrophils to determine whether 1) hypoxia provoked myocardial neutrophil sequestration, 2) neutrophil accumulation could be suppressed by inhibition of lipoxygenase and 3) hypoxic myocardium generated radioimmunoassayable leukotriene B4 (LTB4). Whereas accumulation of 111In-labeled neutrophils by normoxic hearts was minimal, induction of acute myocardial hypoxia by perfusion with hypoxic medium caused a rapid uptake of 111In-labeled neutrophils. Sequestered neutrophils were not released during a subsequent 20-min normoxic perfusion period. Hypoxia-induced neutrophil uptake was prevented by nordihydroguaiaretic acid (NDGA) or diethylcarbamazine (DEC), two structurally different inhibitors of lipoxygenase. Although no radioimmunoassayable LTB4 could be detected in neutrophil-free perfusate from normoxic or hypoxic preparations, hypoxia caused an approximate 2-fold increase in myocardial tissue levels of LTB4. Tissue levels of LTB4 reverted to control values after 20 min of normoxic perfusion. Infusion of exogenous LTB4 also provoked myocardial neutrophil uptake. Viewed collectively, these observations suggest that in isolated buffer-perfused rabbit hearts hypoxia induces LTB4 release from resident myocardial cells, which promotes avid neutrophil sequestration.     

Flow‐mediated dilation in the inactive limb following acute hypoxic exercise

The purpose of this study was to elucidate the effect of acute aerobic exercise performed under hypoxic conditions on flow‐mediated dilation (FMD) in the inactive limb. Seven males participated in the study. The subjects performed two submaximal leg cycling on a semirecumbent ergometer at the same relative intensity (60% peak oxygen uptake) in normoxia [inspired oxygen fraction (FIO₂) = 0·21] and hypoxia (FIO₂ = 0·12–0·13) for 30 min. The brachial artery diameter and blood velocity during exercise were measured via ultrasound, and the antegrade and retrograde shear rates were calculated. Before and 5, 30 and 60 min after exercise, brachial artery FMD was measured in normoxia. FMD was estimated as the percentage increase in peak diameter from the baseline diameter at prior occlusion (%FMD) and as the controlling changes in baseline diameter (the corrected‐%FMD). No difference in antegrade shear rate during exercise was detected between the normoxic and hypoxic conditions, whereas the retrograde shear rate was larger during hypoxic exercise. The %FMD decreased significantly at 5 min after exercise in both normoxia and hypoxia, and it returned to pre‐exercise levels within 60 min of recovery. Significant decreases in FMD at 5 min after exercise had disappeared when the baseline diameter was controlled using an analysis of covariance (the corrected‐%FMD). No significant differences were observed between the normoxic and hypoxic trials in the %FMD and corrected‐%FMD following exercise. These results suggest that hypoxia has no impact on endothelial function in the inactive limb following acute aerobic exercise.     

Multidrug-resistant neuroblastoma cells are responsive to arsenic trioxide at both normoxia and hypoxia

Despite intensive treatment, the outcome of high-risk neuroblastoma patients is poor with acquired multidrug resistance as an important cause. Previously, our group has shown that arsenic trioxide (As(2)O(3)) kills multidrug-resistant neuroblastoma cells in vitro and in vivo at clinically tolerable doses. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we have studied the cytotoxic effect of As(2)O(3) on neuroblastoma cells grown under normoxic as well as hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 2 and 4 mumol/L As(2)O(3) induced evident cell death in the drug-sensitive SH-SY5Y and IMR-32 cells as well as in the multidrug-resistant SK-N-BE(2)c (with a mutated p53) and SK-N-FI cells after 72 hours of exposure. In contrast, the conventional chemotherapeutic drug etoposide showed lowered efficiency in hypoxic IMR-32 cells. In accordance with our previously published results, although not to the same extent as in their normoxic counterparts, Bax is proteolytically cleaved also in neuroblastoma cells exposed to As(2)O(3) at hypoxia. This suggests that similar molecular mechanisms are involved in As(2)O(3)-induced neuroblastoma cell death during hypoxia compared with normoxia. Together, our results support As(2)O(3) as a potential candidate drug as a complement to conventional treatments for high-risk neuroblastoma patients and perhaps also for patients with other multidrug-resistant solid tumors.     

The role of gamma-aminobutyric acid and glutamate for hypoxic ventilatory response in anesthetized rabbits

Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed by a decrease in ventilation. Hypoxia causes changes in brain neurotransmitters depending on its severity and durations. The purpose of this study was to investigate the role of gamma-aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in rabbits. The experiments were performed in peripheral chemoreceptors intact and denervated rabbits anesthetized with Na-pentobarbitate. For intracerebroventricular (ICV) injections of reagents in each animal, cannula was placed in left lateral cerebral ventricle by stereotaxic method. After ICV injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression of respiratory activity. On the other hand, after ICV injection of GABA, breathing of hypoxic gas mixture (8% O(2)-92% N(2)) in both groups produced the hypoxic hyperventilation. After ICV injection of GABA, blockade of GABA(A) receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic hyperventilation observed while the animals were breathing hypoxic gas mixture. Our findings suggest that ICV injection of GABA causes respiratory depression in normoxic conditions, and that it increases ventilation in hypoxic conditions with or without peripheral chemoreceptor impulses by increasing glutamate.     

Effect of Altitude on Erythropoiesis and Oxygen Affinity in Anaemic Patients on Maintenance Dialysis

Abstract. Six anaemic patients with terminal renal failure on maintenance haemodialysis and three healthy control subjects were exposed to altitude hypoxia at Jungfraujoch (3450 m above sea-level). In normal subjects plasma erythropoietin (ESF) as determined by the exhypoxie mouse assay exhibited the expected rise after 24 h (from 0.25 to 3.09%⁶*Fe incorporation). In the patients a smaller but still significant rise was demonstrable (from 0.39 to 2.18%^MFe incorporation), indicating that even severely damaged kidneys with negligible exocrine function retain a definite endocrine reserve for ESF production. For this reason bilateral nephrectomy should be avoided in these patients if possible. 2,3-DPG and P₅₀ (as corrected to pH 7.4) as well as blood pH increased within 24 h after altitude exposure in the control subjects, as described previously. In the patients the two parameters were already elevated under baseline conditions. Upon hypoxic stimulation they rose further (from 44.7 to 56.5 (junoles/10¹¹ Ec. and from 28.6 to 30.1 mmHg respectively), while a definite fall in whole blood pH occurred. High altitude exposure was tolerated remarkably well by the dialyzed patients in spite of the presence of anaemia and severe renal failure.     

Hypoxia Impairs Vasodilation in the Lung

Alveolar hypoxia causes pulmonary vasoconstriction; we investigated whether hypoxia could also impair pulmonary vasodilation. We found in the isolated perfused rat lung a delay in vasodilation following agonist-induced vasoconstriction. The delay was not due to erythrocyte or plasma factors, or to alterations in base-line lung perfusion pressure. Pretreating lungs with arachidonic acid abolished hypoxic vasoconstriction, but did not influence the hypoxia-induced impairment of vasodilation after angiotensin II, bradykinin, or serotonin pressor responses. Progressive slowing of vasodilation followed angiotensin II-induced constriction as the lung oxygen tension fell progressively below 60 Torr. KCl, which is not metabolized by the lung, caused vasoconstriction; the subsequent vasodilation time was delayed during hypoxia. However, catecholamine depletion in the lungs abolished this hypoxic vasodilation delay after KCl-induced vasoconstriction. In lungs from high altitude rats, the hypoxia-induced vasodilation impairment after an angiotensin II pressor response was markedly less than it was in lungs from low altitude rats. We conclude from these studies that (a) hypoxia impairs vasodilation of rat lung vessels following constriction induced by angiotensin II, serotonin, bradykinin, or KCl, (b) hypoxia slows vasodilation following KCl-induced vasoconstriction probably by altering lung handling of norepinephrine, (c) the effect of hypoxia on vasodilation is not dependent on its constricting effect on lung vessels, (d) high altitude acclimation moderates the effect of acute hypoxia on vasodilation, and (e) the hypoxic impairment of vasodilation is possibly the result of an altered rate of dissociation of agonists from their membrane receptors on the vascular smooth muscle.     

Tissue specific modulation of beta-adrenoceptor number in rats with chronic hypoxia with an attenuated response to down-regulation by salbutamol

The number of beta-adrenoceptors and their affinity for the radioligand 125I-labelled cyanopindolol (125I-CYP) were measured in crude membrane preparations of left ventricle, spleen and lung from Wistar rats exposed to 28 days continuous hypoxia. beta-Adrenoceptor density in the left ventricle was not significantly altered after exposure to chronic hypoxia (binding site maxima, Bmax.: normoxic control 36 SEM 5, hypoxic 24.8 SEM 2 fmol/mg of protein). There was no change in beta-adrenoceptor number in the spleen in response to chronic hypoxia (Bmax.: normoxic control 76 SEM 19 fmol/mg of protein, hypoxic 80 SEM 15 fmol/mg of protein). Chronic hypoxia resulted in a significant increase in beta-adrenoceptor number in lung tissue (binding site maxima, Bmax.: normoxic control 406 (SEM 31) fmol/mg of protein; hypoxic 535 (SEM 30) fmol/mg of protein, P less than 0.01 without change in the dissociation constant (KD) of the radioligand. beta-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective beta 2-antagonist). A significant difference was seen in the proportion of beta 1-/beta 2-adrenoceptor subtypes after hypoxia (normoxic control 66 SEM 2.5%, hypoxic 79 SEM 2.4% beta 2-adrenoceptors, P less than 0.01). alpha 1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of alpha 1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (SEM 3), hypoxic 48 (SEM 5) fmol/mg of protein].(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional changes of apparent diffusion coefficient during visual stimulation investigated by diffusion-weighted gradient-echo fMRI

The signal source of apparent diffusion coefficient (ADC) changes induced by neural activity is not fully understood. To examine this issue, ADC-fMRI in response to a visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T. A gradient-echo technique was used for minimizing the coupling between diffusion and background field gradients, which was experimentally confirmed. In the small b-value domain (b=5 and 200 s/mm2), a functional ADC increase was detected at the middle of the visual cortex and at the cortical surface, which was caused mainly by an increase in cerebral blood volume (CBV) and inflow. With higher b-values (b=200 and 1000-1200 s/mm2), a functional ADC decrease was observed in the parenchyma and also at the cortical surface. Within the parenchyma, the ADC decrease responded faster than the BOLD signal, but was not well localized to the middle of visual cortex and almost disappeared when the intravascular signal was removed with a susceptibility contrast agent, suggesting that the decrease in ADC without contrast agent was mostly of vascular origin. At the cortical surface, an average ADC decrease of 0.5% remained after injection of the contrast agent, which may have arisen from a functional reduction of the partial volume of cerebrospinal fluid. Overall, a functional ADC change of tissue origin could not be detected under our experimental conditions.     

Effects of oxygen saturation on BOLD and arterial spin labelling perfusion fMRI signals studied in a motor activation task

Effects of oxygen availability on blood oxygenation level dependent (BOLD) and arterial spin labelling (ASL) perfusion functional magnetic resonance imaging (fMRI) signal changes upon motor activation were studied. Mild hypoxic hypoxia was induced by reducing the inspired oxygen content (FIO(2)) to 12%, decreasing blood oxygen saturation (Y) from 0.99 +/- 0.01 to 0.85 +/- 0.03. The fMRI signal characteristics were determined during finger tapping. BOLD activation volume decreased as a function of declining Y in the brain structures involved in execution of the motor task, however, the BOLD signal increase in activated parenchyma was not influenced by Y. ASL fMRI showed that the baseline CBF of 61.8 +/- 3.6 ml/100 g/min was not affected by hypoxic hypoxia. Similar to the BOLD fMRI, the volume of motor cortex areas displaying increase in perfusion by ASL fMRI decreased, but the signal change due to perfusion increase was not influenced in hypoxia. The present fMRI results show distinct patterns of haemodynamic and metabolic responses in the brain to motor task between normoxia and hypoxia. On one hand, neither BOLD nor ASL fMRI signal changes are influenced by hypoxia during motor activation. On the other hand, hypoxia attenuates increase in both BOLD and perfusion fMRI signals upon finger tapping from the levels determined in normoxia. These observations indicate that haemodynamic and metabolic responses may be heterogeneous in brain during execution of motor functions in mild hypoxia.     

Cytosolic β-glucosidase inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of salidroside in hypoxic rats

The promising benefits of salidroside (SAL) in alleviating high altitude sickness boost investigations on its pharmacokinetics and biological activity. However, the transportation and disposition process of SAL under hypoxic conditions has never been explored. The current study was proposed to investigate the pharmacokinetics of SAL in hypoxic rats and to explore the underlying mechanisms for the distinct metabolic fate of SAL under hypoxia. Pharmacokinetic studies on SAL was conducted in both hypoxic and normoxic rats. The transport properties of SAL were investigated on both hypoxic and normoxic Caco-2 monolayer models. Enzymes involved in SAL metabolism were identified and the effects of hypoxia on these enzymes were assessed by real-time PCR, western blotting analyses, and rat liver homogenate incubation. The renal clearance (CL_r) of SAL, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in both hypoxic and normoxic rats were also determined for renal function assessment. It was found that the systemic exposure of SAL in hypoxic rats was remarkably higher than that in normoxic rats. The barrier function of Caco-2 monolayer was weakened under hypoxia due to the impaired brush border microvilli and decreased expression of tight junction protein. Hepatic metabolism of SAL in hypoxic rats was attenuated due to the reduced activity of cytosolic β-glucosidase (CBG). Moreover, CL_r of SAL was reduced in hypoxic rats due to the suppressed ERPF. Our findings suggest the potential need for dose-adjustment of SAL or its structural analogs under hypoxic conditions.

CBG inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of SAL in hypoxic rats.     

Total and hindlimb O2 uptake and blood flow in hypoxic dogs given dopamine

Cardiovascular interactions between dopamine and hypoxia were examined in 8 anesthetized, paralyzed dogs ventilated at constant rates. Total and hindlimb (less paw) O2 uptake, blood flow, and vascular resistance were measured with and without dopamine infusion of 10 micrograms/kg . min during both normoxic and hypoxic ventilation. Another 8 dogs were similarly treated after beta-blockade with propranolol infusion (1 mg/kg). During the baseline period, normoxic dopamine significantly increased total O2 uptake, cardiac output, and stroke volume, and significantly decreased total vascular resistance in the control group. Hypoxia decreased total O2 uptake, cardiac output, and heart rate but increased total vascular resistance. Dopamine reversed each of these hypoxic changes and restored total O2 uptake to normoxic levels. Hindlimb measurements were not significantly changed by dopamine or hypoxia in the control group. During hypoxia, beta-blockade abolished dopamine's effects except for the decrease in total vascular resistance. The improvement in cardiac output and O2 transport by dopamine infusion resulted from increased stroke volume during normoxia and from increased heart rate during hypoxia.     

Effects of resistance training under hypoxic conditions on muscle hypertrophy and strength

It has been reported that exercise under hypoxic conditions elevates acute growth hormone secretion after exercise compared with that under normoxic conditions. This study examined the influence of resistance training under moderate hypoxic conditions on muscle thickness, strength and hormonal responses. Thirteen healthy men were assigned into two groups matched for physical fitness level and then randomized into two groups that performed exercise under normoxic (FiO₂ = 20·9%) or hypoxic (FiO₂ = 12·7%) conditions. Three sets of elbow extensions with unilateral arm were performed to exhaustion at a workload of a 10 repetition maximum with 1‐minute intervals for 3 days per week for 8 weeks. The thickness of the biceps and triceps brachii was determined using B‐mode ultrasound before and after training. Blood sampling was carried out before and after exercise, as well as during the first and last training sessions. Increase in the thickness of the triceps brachii in trained arm was significantly greater in the hypoxic group than in the normoxic group. The 10 repetition maximum was significantly increased not only in the trained arm but also in the untrained arm in both groups. Serum growth hormone concentrations after exercise were significantly higher in the hypoxic group than in the normoxic group on both the first and last training sessions. These findings suggest that hypoxic resistance training elicits more muscle hypertrophy associated with a higher growth hormone secretion, but that the greater muscle hypertrophy did not necessarily contribute a greater gain of muscle strength.     

Cerebrovascular response to acute hypocapnic and eucapnic hypoxia in normal man

Alterations in human cerebral blood flow and related blood constituents were studied during exposure to acute hypoxia. Observations were made during serial inhalation of decreasing O(2) concentrations with and without maintenance of normocarbia, during 8 min inhalation of 10% O(2), and after hyperventilation at an arterial P(O2) of about 40 mm Hg. In the range of hypoxemia studied, from normal down to arterial P(O2) of about 40 mm Hg, the magnitude of the cerebral vasodilator response to hypoxia appeared to be largely dependent upon the coexisting arterial CO(2) tension. The mean slope of the increase in cerebral blood flow with decreasing arterial O(2) tension rose more quickly (P < 0.05) when eucapnia was maintained when compared with the slope derived under similar hypoxic conditions without maintenance of eucapnia. When 12 subjects inhaled 10% oxygen, cerebral blood flow rose to more than 135% of control in four whose mean decrease in arterial CO(2) tension was - 2.0 mm Hg. The remaining eight had flows ranging from 97 to 120% of control, and their mean decrease in CO(2) tension was - 5.1 mm Hg. When mean arterial P(O2) was 37 mm Hg, hyperventilation was carried out in 10 subjects. Arterial P(O2) increased insignificantly, arterial P(CO2) declined from 34 to 27 mm Hg (P < 0.05), and cerebral blood flow which had been 143% of control decreased to 109%, a figure not significantly different from control.These data demonstrate the powerful counterbalancing constrictor effects of modest reductions in CO(2) tension on the vasodilator influence of hypoxia represented by arterial P(O2) reductions to about 40 mm Hg. Indeed, mild hyperventilation completely overcame the vasodilator effect provided by an arterial O(2) tension as low as 40 mm Hg. The effects of hypoxia on the control of the cerebral circulation must be analyzed in terms of the effects of any associated changes in CO(2) tension.     

高原低氧对大鼠心肺组织超微结构的影响

背景：研究表明快速进入高原地区时,机体不可避免地会受到不同程度的损伤,以心肺损伤较显著。目的：观察低氧习服对高原低氧大鼠心肺组织的超微结构影响。方法：将SD大鼠分别为进行高原低氧干预1,3和30d,并设置对照组。3个高原低氧组由海拔5m的西安途中耗时1d带到海拔2700m的青海格尔木地区、途中耗时3,30d分别带到海拔4500m的西藏那曲地区,观察各时间点心肺标本的组织学变化。结果与结论：急性高原低氧1,3d组肺组织显微和超微结构出现明显的间质性肺水肿和肺泡性肺水肿,其心脏组织光镜下大鼠各室壁心肌细胞均可见不同程度的浊肿、空泡变性、溶解坏死及间质水肿等,电镜下可见心肌细胞线粒体肿胀,肌浆网扩张,肌原纤维溶解,细胞内外水肿等,急性高原低氧3d上述改变右室壁较左室壁明显,而低氧习服后高原低氧30d组间质性水肿和则肺水肿明显减轻。结果证实,高原急性缺氧可造成大鼠间质性肺水肿和肺泡型肺水肿,并引起以右心室为主的全心性损伤,经过高原低氧习服后心肺组织病变明显减轻。