Myocardial electrolytes in hypobaric hypoxia

Male, white rats (Holtzmann) were exposed to 7,200 m in a barometric chamber for six hours a day for three weeks. Control rats were kept at a sea level altitude of 200 m in Peoria, Illinois. At the end of the exposure period the rats were guillotined and their hearts removed. Approximately equal size strips were cut out of the right ventricles (RV), septa (S) and left ventricles (LV) and weighed on a Mettler balance. All heart pieces were dried overnight in a 40°C oven and reweighed following cooling. They were digested in concentrated nitric acid, diluted with distilled water; and sodium, potassium, calcium and magnesium were determined by atomic absorption spectrophotometry. RV and S muscle from the high altitude rats (HA) had a significantly higher water content. RV muscle from HA rats contained significantly more Na⁺, K⁺ and Ca⁺⁺ and less Mg⁺⁺ than sea level controls (SL). LV muscle from HA animals contained significantly less Na⁺ than SL controls. Within the HA hearts, the RV contained sïgnificantly more Na⁺, K⁺ and Ca⁺⁺ and significantly less Mg⁺⁺ than the S or LV. Evidence indicates that chronic high altitude exposure results in significant alterations in electrolyte distribution throughout the heart.Presented at the Seventh International Biometeorological Congress, 17–23 August 1975, College Park, Maryland, U.S.A.     

Experimental cardiac necrosis in hypobaric and anemic hypoxia.

Resistance to isoproterenol-induced cardiac necrosis (IPRO) was compared in rats exposed to two types of hypoxia (i.e., hypobaric and anemic). IPRO was induced by two consecutive, subcutaneous injections of isoproterenol (80 mg/kg) at 24-h intervals. The animals were killed on the third day and the severity of the lesion was evaluated on a 0 (no damage) to 4 (severely damaged) scale. White male rats (HA) were exposed in a barometric chamber to a simulated altitude of 7,000 m (307 mmHg) for 4 h/day for 24 days. Two groups of control rats were kept at sea level; one group (SLA) was the same age and one group (SLW) was the same weight as the altitude-exposed rats. The HA rats were significantly more resistant to IPRO with a mean necrogenic rating of 1.8 compared to 3.3 for the SLA and SLW rats. Infant rats (AA) were made anemic by feeding full-cream milk and glucose for 100 days after weaning. Two groups of control animals were fed a standard laboratory diet; one group (AC) was the same age and one group (AW) was the same weight as the AA rats. There was no significant difference in the necrogenic ratings of the AA (3.3), AC (3.5), or WC (3.7) hearts. Thus, hypobaric hypoxia affords some protection against IPRO which is not afforded by anemic hypoxia. Similarities and differences in the two hypoxias are discussed.     

Brain adaptation to chronic hypobaric hypoxia in rats.

Rats were exposed to hypobaric hypoxia (0.5 atm) for up to 3 wk. Hypoxic rats failed to gain weight but maintained normal brain water and ion content. Blood hematocrit was increased by 48% to a level of 71% after 3 wk of hypoxia compared with littermate controls. Brain blood flow was increased by an average of 38% in rats exposed to 15 min of 10% normobaric oxygen and by 23% after 3 h but was not different from normobaric normoxic rats after 3 wk of hypoxia. Sucrose space, as a measure of brain plasma volume, was not changed under any hypoxic conditions. The mean brain microvessel density was increased by 76% in the frontopolar cerebral cortex, 46% in the frontal motor cortex, 54% in the frontal sensory cortex, 65% in the parietal motor cortex, 68% in the parietal sensory cortex, 68% in the hippocampal CA1 region, 57% in the hippocampal CA3 region, 26% in the striatum, and 56% in the cerebellum. The results indicate that hypoxia elicits three main responses that affect brain oxygen availability. The acute effect of hypoxia is an increase in regional blood flow, which returns to control levels on continued hypoxic exposure. Longer-term effects of continued moderate hypoxic exposure are erythropoiesis and a decrease in intercapillary distance as a result of angiogenesis. The rise in hematocrit and the increase in microvessel density together increase oxygen availability to the brain to within normal limits, although this does not imply that tissue PO2 is restored to normal.     

Lymphopoietic characteristics in acute hypobaric hypoxia

10 healthy men were examined, that underwent a 48 hours hypobaric (acute) hypoxia in the climate chamber "Taba?", with conditions corresponding to those at an altitude of 4,000 m. The "ascent" and "descent" were performed correspondingly within 30 minutes. Increased share of dying lymphocytes and frequency of chromosomal aberrations in these were found in addition to an elevated activity of nucleolar organizers and to changed morphological patterns of argentophilic nucleoli. T- and B-lymphocyte contents remained unchanged. The role of the lymphopoietic alterations in autoimmune complications and of hemopoietic disorders in the mountains is discussed.     

间歇性低压低氧与连续性低压低氧对大鼠血液动力学作用的比较(英文)

本研究旨在探讨并比较慢性间歇性低压低氧（intermitten thypobaric hypoxia,IHH）和慢性连续性低压低氧（continuous hypobaric hypoxia,CHH）对大鼠血液动力学作用的影响。40只成年Sprague—Dawley大鼠随机分为5组：对照组（CON）,28天IHH处理组（IHH28）,42天IHH处理组（IHH42）,28天CHH组（CHH28）和42天CHH组（CHH42）。IHH火鼠于低压氧舱分别接受28或42天模拟5000m海拔高度低氧（11．1％O2）处理、每天6h。CHH处理大鼠生活在低压氧舱环境中,除每天半小时常氧供食、供水和清洁外,其余时间均分别接受时程为28或42天的模拟5000m海拔高度低氧（11．1％O2）处理。每周定时测定大鼠体重。通过导管法测定基础常氧和急性低氧状态下的血液动力学,包括半均动脉压（meanartery blood pressure,MAP）、心率（heartrate,HR）、左审收缩峰压（1eft ventricular systolic pressure,LVSP）、正负左率最人压力变化速率（maximum change rate of left ventricular pressure,±LVdP／dtmax）。通过生物化学方法测定大鼠心肌超氧化物岐化酶活性和丙二醛含量。并分别测定全心、左心室和右心室重量。结果显示：（1）CHH42大鼠基础HR和MAP低于CON,IHH和CHH28大鼠（P〈0．05）。（2）IHH大鼠表现出明显的抗心肌缺氧／复氧损伤作用,表现为急性低氧状态下的HR、MAP、LVSP和＋LVdP/dtmax,改变明显低于CON大鼠（P〈0．05）;CHH大鼠表现出更为明显的抗急性低氧心脏保护作用,表现为急性低氧的HR、MAP、LVSP和±LVdP/dtmax;改变明显低于CON和IHH火鼠（P〈0．05）,但出现复氧损伤作用,表现为复氧过程中血液动力学的恢复明显低于CON和IHH大鼠（P〈0．05）。（3）与CON大鼠相比较,IHH和CHH大鼠心肌抗氧化能力明显增强（P〈0．05,P〈0．01）。（4）与IHH和CON大鼠相比较,CHH大鼠表现明显的右心室肥厚（P〈0．01）。结果表明,IHH可诱导有效的心脏保护作用,而无明显的不良反应,因而具有潜在的实际应用价值。     

Determinants of erythropoietin release in response to short-term hypobaric hypoxia.

We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P < 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes > or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.     

Transient hypobaric hypoxia improves spatial orientation in young rats

To achieve a better understanding of learning and declarative memory under mild transient stress, we investigated the effect of brief hypobaric hypoxia on spatial orientation in rats. Young male Wistar rats aged 30 days were exposed for 60 min to hypobaric hypoxia, simulating an altitude of 7,000 m (23,000 ft) either shortly prior to attempting or after mastering an allothetic navigation task in the Morris water maze with a submerged platform. The post-hypoxic group performed significantly better in the navigation task than the control animals (the mean difference in escape latencies was 11 seconds; P=0.0033, two-way ANOVA with repeated measures, group x session). The experimental group also achieved a remarkably higher search efficiency (calculated as a percentage of successful trials per session), especially during the first four days following hypoxic stress (P=0.0018). During the subsequent training, the post-hypoxic group performed better than the control animals, whilst the efficiency levels of both groups progressively converged. Spatial memory retention and recall of well-trained rats were not affected by the transient hypobaric hypoxia. These results indicate that brief hypobaric hypoxia enhances rats' spatial orientation. Our findings are consistent with several studies, which also suggested that mild transient stress improves learning.     

PAF antagonists inhibit pulmonary vascular remodeling induced by hypobaric hypoxia in rats.

Chronic hypoxia causes pulmonary hypertension and pulmonary vascular remodeling in rats. Because platelet-activating factor (PAF) levels increase in lung lavage fluid and in plasma from chronically hypoxic rats, we examined the effect of two specific, structurally unrelated PAF antagonists, WEB 2170 and BN 50739, on hypoxia-induced pulmonary vascular remodeling. Treatment with either agent reduced hypoxia-induced pulmonary hypertension and right ventricular hypertrophy at 3 wk of hypoxic exposure (simulated altitude 5,100 m) but did not affect cobalt (CoCl2)-induced pulmonary hypertension. The PAF antagonists had no effect on the hematocrit of normoxic or chronically hypoxic rats or CoCl2-treated rats. Hypoxia-induced pulmonary hypertension was associated with an increase in the vessel wall thickness of the muscular arteries and reduction in the number of peripheral arterioles. In WEB 2170-treated rats, these changes were significantly less severe than those observed in untreated chronically hypoxic rats. PAF receptor blockade had no acute hemodynamic effects; i.e., it did not affect pulmonary arterial pressure or cardiac output nor did it affect the magnitude of acute hypoxic pulmonary vasoconstriction in awake normoxic or chronically hypoxic rats. Isolated lungs from chronically hypoxic rats showed a pressor response to the chemotactic tripeptide N-formyl-Met-Leu-Phe (fMLP) and an increase in the number of leukocytes lavaged from the pulmonary circulation. In vivo treatment with WEB 2170 significantly reduced the fMLP-induced pressor response compared with that observed in isolated lungs from untreated chronically hypoxic rats. These results suggest that PAF contributes to the development of chronic pulmonary hypertension induced by chronic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptation to chronic hypobaric hypoxia and sexual hormones

The role of the gonads and their hormones on body weight was studied in rats of both sexes submitted to chronic hypoxia and their controls at sea level atmospheric pressure. Intact rats were exposed to either 4 700 or 6 000 m simulated altitude in a hypopressure chamber. Castrated rats and castrated rats daily injected with either 0.5 mg of testosterone or 20 microgram of estradiol or the vehicle, were exposed to the higher altitude. The rat weight was recorded for a period of at least eight weeks. All groups of hypoxic male animals increased their weight significantly less than the controls at sea level. Also in castrated females and in castrated injected with testosterone or the vehicle the same pattern of weight curves was observed. On the contrary, groups of intact females and castrated females injected with estradiol did not show significant differences between hypoxic and control animals. Only in a group of smaller intact females (50-80 g) the body weight increase was significantly diminished by exposure to either 4 700 or 6 000 m simulated altitude.     

Thyroid function during intermittent exposure to hypobaric hypoxia

Circulatory levels of triiodothyronine (T₃) and thyroxine (T₄) and their kinetics were studied in rabbits exposed to intermittent hypobaric hypoxia (5200 m, 395 mm Hg,PO₂ 83 mm Hg) 6 h daily for 5 weeks in a decompression chamber maintained at room temperature of 22°–24° C. Kinetics of T₃ and T₄ were studied on days 21 and 28 of hypoxic exposure. The T₃ and T₄ values were found to be significantly lower on day 8 of exposure to hypoxia compared to the pre-exposure values. The decreased levels were maintained throughout the entire period of hypoxic stress. The metabolic clearance rate, production rate, distribution space and extrathyroidal T₃ and T₄ pools were significantly decreased in animals under hypoxic stress compared to the control animals. The decline in thyroid hormone levels and their production in rabbits under hypoxic stress indicate an adaptive phenomenon under conditions of low oxygen availability.     

Gender alters impact of hypobaric hypoxia on adductor pollicis muscle performance.

Recently, we reported that, at similar voluntary force development during static submaximal intermittent contractions of the adductor pollicis muscle, fatigue developed more slowly in women than in men under conditions of normobaric normoxia (NN) (Acta Physiol Scand 167: 233-239, 1999). We postulated that the slower fatigue of women was due, in part, to a greater capacity for muscle oxidative phosphorylation. The present study examined whether a gender difference in adductor pollicis muscle performance also exists during acute exposure to hypobaric hypoxia (HH; 4,300-m altitude). Healthy young men (n = 12) and women (n = 21) performed repeated static contractions at 50% of maximal voluntary contraction (MVC) force of rested muscle for 5 s followed by 5 s of rest until exhaustion. MVC force was measured before and at the end of each minute of exercise and at exhaustion. Exhaustion was defined as an MVC force decline to 50% of that of rested muscle. For each gender, MVC force of rested muscle in HH was not significantly different from that in NN. MVC force tended to decline at a faster rate in HH than in NN for men but not for women. In both environments, MVC force declined faster (P < 0.01) for men than for women. For men, endurance time to exhaustion was shorter (P < 0.01) in HH than in NN [6.08 +/- 0.7 vs. 8.00 +/- 0.7 (SE) min]. However, for women, endurance time to exhaustion was similar (not significant) in HH (12.86 +/- 1.2 min) and NN (13.95 +/- 1.0 min). In both environments, endurance time to exhaustion was longer for women than for men (P < 0.01). Gender differences in the impact of HH on adductor pollicis muscle endurance persisted in a smaller number of men and women matched (n = 4 pairs) for MVC force of rested muscle and thus on submaximal absolute force and, by inference, ATP demand in both environments. In contrast to gender differences in the impact of HH on small-muscle (adductor pollicis) exercise performance, peak O(2) uptake during large-muscle exercise was lower in HH than in NN by a similar (P > 0.05) percentage for men and women (-27.6 +/- 2 and -25.1 +/- 2%, respectively). Our findings are consistent with the postulate of a higher adductor pollicis muscle oxidative capacity in women than in men and imply that isolated performance of muscle with a higher oxidative capacity may be less impaired when the muscle is exposed to HH.     

Effect of hypobaric hypoxia on immune function in albino rats

 The effect of exposure to hypoxia on macrophage activity, lymphocyte function and oxidative stress was investigated. Hypoxia enhanced peritoneal macrophage activity as revealed by enhanced phagocytosis and free radical production. There was no significant change in antibody titres to sheep red blood cells in either serum or spleen during hypoxia. However, there was a considerable reduction in the delayed-type hypersensitivity response to sheep red blood cells, indicating the impairment of T-cell activity. Hypoxia decreased the blood glutathione (reduced) level and increased plasma malondialdehyde by a factor of about 2. It is therefore speculated that hypoxia imposes an oxidative stress leading to decreased T-cell acivity. Received: 1 September 1997 / Accepted: 22 May 1998     

Cytospectrophotometric study of hemoglobin in human erythrocytes. II. Methemoglobin formation in acute hypobaric hypoxia

The percentage of erthrocytes with thorn-shaped protuberances--echinocytes--was calculated in the blood smears of 10 healthy men before and after a 48 hour sharp hypobaric hypoxia in the climatic chamber of Tabai. The absorbtion spectra at the range 400-650 nm were investigated in the smooth erythrocytes and echinocytes. The methemoglobin content in the echinocytes is higher than in the smooth erythrocytes. The sharp hypobaric hypoxia results in the increase in the percentage of echinocytes and erythrocytes with fetal hemoglobin, in the change of osmotic stability and acidic resistance of erythrocytes, and in the rise of peroxid oxidation of lipids. The role of methemoglobin production upon a sharp hypobaric hypoxia is discussed.     

Intermittent hypobaric hypoxia applicability in myocardial infarction prevention and recovery

Intermittent hypobaric hypoxia (IHH) has been the focus of important research in cardioprotection, and it has been associated with several mechanisms. Intermittent hypobaric hypoxia inhibits prolyl hydroxylases (PHD) activity, increasing the stabilization of hypoxia-inducible factor-1 (HIF-1) and activating crucial adaptative genes. It has been hence suggested that IHH might be a simple intervention, which may offer a thoughtful benefits to patients with acute myocardial infarction and no complications. Nevertheless, several doubts exist as to whether IHH is a really safe technique, with little to no complications in post-myocardial infarction patients. Intermittent hypobaric hypoxia might produce instead unfavourable changes such as impairment of vascular hemodynamics and hypertensive response, increased risk of hemoconcentration and thrombosis, cardiac rhythm perturbations, coronary artery disease and heart failure, insulin resistance, steatohepatitis and even high-altitude pulmonary oedema in susceptible or nonacclimatized patients. Although intermittent and chronic exposures seem effective in cardioprotection, IHH safety issues have been mostly overlooked, so that assorted concerns should be raised about the opportunity to use IHH in the post-myocardial infarction period. Several IHH protocols used in some studies were also aggressive, which would hamper their widespread introduction within the clinical practice. As such, further research is needed before IHH can be widely advocated in myocardial infarction prevention and recovery.     

Platelets and leukocytes in the lungs after acute hypobaric hypoxia

To determine if decompression from sea level causes aggregation and embolization of platelets or leukocytes to the lungs, we have measured the accumulation of 51Cr-labeled platelets or 111In-labeled leukocytes in the lungs of rabbits decompressed to 440 or 350 Torr for 18 or 40 h. To be certain that any increased accumulation of labeled platelets (or leukocytes) in the lungs was not just caused by an increased pulmonary blood volume we also labeled the rabbits red blood cells with 59Fe. There was no detectable accumulation of labeled platelets in the lungs on decompression. In control animals there were 22 times as many labeled leukocytes in the lungs as could be accounted for by the volume of blood in the lungs. In experimental animals at 326 Torr for 18 h this figure was reduced to 13.6. Hypobaric hypoxia caused an increase in circulating granulocytes from a mean of 3.3 +/- 1.6 X 10(9)/l to 5.3 +/- 2.1 X 10(9)/l. (P less than 0.005). Our results suggest that decompressions to 6,100 m for 18 h does not cause platelet sequestration in the lungs but does cause a significant reduction in leukocytes in the lungs and a peripheral granulocytosis.     

Sodium citrate ingestion and muscle performance in acute hypobaric hypoxia

Eight subjects were studied on four occasions following ingestion of a 300-ml solution containing either sodium citrate (C, 0.4g · kg^–1 body mass) or placebo (P, sodium chloride 0.045 g · kg^–1 body mass), at local barometric pressure (N, P _B approximately 740 mmHg, 98.7 kPa) or hypobaric hypoxia (HH, P _B = 463 mmHg, 61.7 kPa). At 2 h after ingestion of the solution, the subjects performed prolonged isometric knee-extension at 35% of the maximal voluntary contraction (MVC) measured either in N or HH. Results showed that ingestion of C led to an improvement in muscle endurance (P < 0.01). However, this increase in endurance time for knee extensor muscles was only significant in N ( +22%, P < 0.05, compared to + 15%, NS, at N and HH, respectively). Following ingestion of sodium citrate, pre-exercise bicarbonate concentrations and pH levels were significantly higher than those measured after P ingestion. A significant treatment effect was observed for blood lactate concentrations with values higher for C than for P after 4, 6 and 10 min of recovery (P < 0.05). Electromyographic signals (EMG) were obtained from the vastus lateralis muscle during the prolonged isometric contraction at 35% MVC. The mean power frequency (MPF) significantly decreased in time under both N-P and N-C conditions. In HH, no significant decrease in MPF was observed with time. The results suggest that C ingestion was an ergogenic aid enhancing endurance during a sustained isometric contraction. In addition, it is suggested that fatigue during prolonged isometric contraction in HH was not directly related to factors determining the EMG signs of fatigue.