慢性间歇性低压低氧对大鼠动脉血管收缩功能的影响

本研究旨在探讨慢性间歇性低压低氧(chronicintermittent hypobaric hypoxia,CIHH)对大鼠胸主动脉和肺动脉收缩功能的影响及其机制.雄性Sprague-Dawley大鼠随机分为4组:CIHH处理14天组(CIHH 14)、28天组(CIHH 28)、42天组(CIHH 42)和对照组(...     

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。     

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.     

Facilitation of chronic intermittent hypobaric hypoxia on carotid sinus baroreflex in anesthetized rats

Our previous study showed that chronic intermittent hypobaric hypoxia (CIHH) could prevent decreases in systemic arterial blood pressure (SABP) during acute hypoxia. However, the mechanism was not clear. The purpose of the present study was to observe whether the carotid sinus baroreflex (CSB) was involved in the antagonizing effect of CIHH on SABP decrease induced by acute hypoxia and to explore the underlying mechanism using perfusion technique in rat isolated carotid sinus area. After 14-day and 28-day CIHH exposure, the CSB in rats was enhanced markedly, manifesting as increases in PS and RD, and decreases in TP and SP. This facilitation of CSB was partly abolished by Glibenclamide (Gli, 10 μM), a K ATP channel blocker, but was not influenced by L-NAME (100 μM), a nitric oxide synthase (NOS) inhibitor. The results of the study suggested that CIHH facilitated CSB through opening the K ATP channels in carotid sinus of anesthetic rats and might be one of mechanisms of CIHH keeping SABP homeostasis during acute hypoxia.     

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     

Different degrees of lipid peroxidation in the CNS of young and adult rats exposed to short-term hypobaric hypoxia.

The authors studied the effect of short-term (20 min) hypobaric hypoxia at simulated altitudes of 7000 and 9000 m on the peroxidation of lipids in the cerebral cortex, subcortical formations, medulla oblongata and cerebellum of the laboratory rat. In 5- and 21-day-old rats, increased lipoperoxidation was recorded in all the studied regions of the brain. Differences were observed in sensitivity to the degree of hypoxia. In 5-day-old rats the response to both exposures was the same, but in 21-day-old animals exposure at 7000 m stimulated peroxidation in the cerebral cortex only (at 9000 m in all the parts of the CNS examined). In 35-day-old and adult rats, changes in the malondialdehyde concentration were likewise found after exposure at 9000 m, but not in every compartment (in 35-day-old rats in the cerebral cortex and subcortical formations and in adult rats in the cerebral cortex). In young rats, 30 and 60 min after exposure to hypoxia the malondialdehyde concentration was still higher than in older animals.     

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.     

The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters

The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood rheology is not completely investigated. We designed this study to determine the effect of CLTIHH on blood rheology parameters. Present study was performed in 16 male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5 days/week, 5 weeks). The control rats stayed in the same environment as the CLTIHH rats but they breathed room air. In the blood samples aspirated from the heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen concentration, erythrocyte rigidity index and oxygen delivery index were determined. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen concentration values in the CLTIHH group were found to be higher than those of the control group. However, no significant difference was found in erythrocyte rigidity index and oxygen delivery index between the groups. Our results suggested that CLTIHH elevated whole blood viscosity by increasing plasma viscosity, fibrinogen concentration and hematocrit value without effecting the erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high altitude exposure and some severe obstructive sleep apnea (OSA) patients may be responsible for hemorheologic changes in those subjects.     

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.     

Protective effects of polyunsatutared fatty acids supplementation against testicular damage induced by intermittent hypobaric hypoxia in rats

Background

Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of the work was to test whether PUFA supplementation attenuates oxidative damage in testis by reinforcing the antioxidant defense system. The animals were divided into four groups (7 rats per group): normobaric normoxia (~750 tor; pO2 156 mmHg; Nx); Nx + PUFA, supplemented with PUFA (DHA: EPA = 3:1; 0.3 g kg⁻¹ of body weight per day); hypoxic hypoxia (~428 tor; pO2 90 mmHg; Hx) and, Hx + PUFA. The hypoxic groups were exposed in 4 cycles to 96 h of HH followed by 96 h of normobaric normoxia for 32 days. Total antioxidant capacity (FRAP) and lipid peroxidation (malondialdehyde, MDA) in plasma and reduced (GSH)/oxidized glutathione (GSSG) ratio, tissue lipid peroxidation (TBARS) and antioxidant enzymes activity were assessed at the end of the study in testis. Also, SIRTUIN 1 and HIF-1 protein expression in testis were determined.

Results

IHH increased lipid peroxidation in plasma and HIF-1 protein levels in testis. In addition, IHH reduced FRAP levels in plasma, antioxidant enzymes activities and SIRTUIN 1 protein levels in testis. PUFA supplementation attenuated these effects, inducing the increases in FRAP, in the antioxidant enzymes activity and HIF-1 levels.

Conclusions

These results suggest that the IHH model induces a prooxidant status in plasma and testis. The molecular protective effect of PUFA may involve the induction of an antioxidant mechanism.     

Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity

Abnormal activation of mitochondrial translocator protein (TSPO) contributes to arrhythmogenesis during cardiac metabolic compromise; however, its role in the antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas this condition was seldom observed in rats with 14 days of chronic intermittent hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias incidence in normoxic rats, but did not change the CIHH‐mediated antiarrhythmic effects. Abrupt and excessive elevation of TSPO activity was positively linked to ischaemic VF, and CIHH preserved TSPO activity during ischaemia. The preservation of TSPO activity by CIHH also contributed to the maintenance of intracellular Ca homeostasis. These results suggest that the blunt sensitivity of TSPO to ischaemic stress may be responsible for the antiarrhythmic effects by CIHH.     

Melatonin protects the heart, lungs and kidneys from oxidative stress under intermittent hypobaric hypoxia in rats

Melatonin (N-acetyl-5-methoxytryptamine) is the main secretory product of the pineal gland in all mammals including humans, but it is also produced in other organs. It has been previously demonstrated to be a powerful organ-protective substance under oxidative stress conditions. The aim of this study was to evaluate the protective effect of melatonin in several organs such as heart, lung, kidney, and of the reproductive system, such as testis and epididymis in animals exposed to intermittent hypobaric hypoxia and therefore exposed to oxidative stress and analyzed by lipid peroxidation. Ten-week-old male Wistar rats were divided into 6 groups for 96 hours during 32 days under: 1) Normobaric conditions, 2) plus physiologic solution, 3) plus melatonin, 4) intermittent hypobaric hypoxia, 5 plus physiologic solution and 6) plus melatonin. The animals were injected with melatonin (10 mg/kg body weight) at an interval of 96 hours during 32 days. Results indicated that melatonin decreased lipid peroxidation in heart, kidneys and lung under intermittent hypobaric hypoxia conditions. However, it did not exhibit any protective effect in liver, testis, epididymis and sperm count.     

Seasonal changes in plasma and aortic lipids in young rats

In young non-exercised rats, plasma triglyceride and plasma phospholipid levels increased in summer and low density lipoprotein cholesterol (LDL-C) increased in winter. As for lipids samples from the wall of the aorta, total cholesterol, cholesteryl ester and triglyceride decreased in summer and phospholipid decreased in winter. Exercise diminished the gain in body mass (delta m) and suppressed seasonal changes in the levels of LDL-C and plasma triglyceride. Seasonal changes in the aorta lipids in this case were similar to those found in non-exercised animals. The values of total energy intake (Q) and of delta m.Q-1 were found to change with season in both non-exercised and exercised rats. Seasonal changes in plasma and in aorta lipids observed in these animals ran in parallel with the respective levels of delta m.Q-1 and/or of Q. The training effect on the lipid values detected in summer and/or in winter was also found to be dependent on the reduction in delta m.Q-1 with exercise. In the non-exercised and in the exercised animals, plasma phospholipid was associated with aorta phospholipid and inversely related to aorta cholesteryl ester and aorta triglyceride. The relationship between these estimations suggests that an increase in the plasma phospholipid in summer would remove non-polar lipids from the walls of the aortae.     

间歇性低压低氧对过氧化氢心肌细胞损伤的保护作用

目的:观察慢性间歇性低压低氧对过氧化氢所致心肌细胞损伤的保护作用及其机制。方法:雄性豚鼠20只,随机分为两组(n=10):对照组(non-IHH)、低氧组(IHH)。低氧组豚鼠于低压氧舱接受28 d(海拔5 000 m、每天6 h)的低压低氧处理。胶原酶方法急性分离心肌细胞。细胞动缘探测系统测定过氧化氢对各组细胞收缩力的变化。生化方法测定各组丙二醛(MDA)、乳酸脱氢酶(LDH)及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的变化。结果:①过氧化氢可使心肌细胞出现收缩、舒张紊乱,但IHH处理使其出现的潜伏期明显延长。②给予过氧化氢(300μmol/L,10 min)使来自于non-IHH或IHH的心肌细胞LDH、MDA含量均明显增加,但IHH心肌细胞LDH、MDA含量明显低于non-IHH心肌细胞的LDH、MDA含量。③经IHH处理组的心肌细胞SOD,CAT活性均明显高于non-IHH组。给予过氧化氢使来自于non-IHH或IHH的心肌细胞SOD,CAT活性均明显降低,但IHH心肌细胞SOD,CAT活性明显高于non-IHH心肌细胞的SOD,CAT活性。结论:IHH具有对抗过氧化氢心肌细胞损伤的作用,可能与其增强抗氧化酶活性有关。     

Myosin heavy chain composition of skeletal muscles in young rats growing under hypobaric hypoxia conditions.

This study investigated the effects of voluntary wheel running on the myosin heavy chain (MHC) composition of the soleus (Sol) and plantaris muscles (Pla) in rats developing under hypobaric choronic hypoxia (CH) conditions during 4 wk in comparison with those of control rats maintained under local barometric pressure conditions (C) or rats pair-fed an equivalent quantity of food to that consumed by CH animals (PF). Compared with C animals, sedentary rats subjected to CH conditions showed a significant decrease in type I MHC in Sol (-12%, P < 0.01). Although strongly decreased under hypoxia, spontaneous running activity increased the expression of type I MHC (P < 0.01) so that no difference in the MHC profile of Sol was shown between CH active and C active rats. The MHC distribution in Sol of PF rats was not significantly different from that found in C animals. CH resulted in a significant decrease in type I (P < 0.01) and type IIA (P < 0.005) MHC, concomitant with an increase in type IIB MHC in Pla (P < 0.001), compared with C and PF animals. In contrast to results in Sol muscle, this slow-to-fast shift in the MHC profile was unaffected by spontaneous running activity. These results suggest that running exercise suppresses the hypoxia-induced slow-to-fast transition in the MHC expression in Sol muscles only. The hypoxia-induced decrease in food intake has no major influence on MHC expression in developing rats.     

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.     

Effect of intermittent chronic exposure to hypoxia on feeding behaviour of rats

Healthy albino male rats were exposed to a simulated high altitude (HA) equivalent to 25000 ft (7620 m) for 6 h daily, continuously for 21 days to study the feeding behaviour. The 24-h food and water intake and body weight once in 3 days were recorded. Blood samples were drawn once a week from the retro-orbital venous plexus for blood sugar analysis. All the parameters were recorded before, during and after exposure to simulated HA. The results show a decrease in 24-h food and water intake and decreased gain in body weight during hypoxic exposure, which showed a tendency to come back to control during the post-exposure period. The blood sugar reflected a state of mild hyperglycaemia during exposure to HA.