Hyperoxia Research Articles

Differential effect of intrauterine hypoxia on caspase 3 and DNA fragmentation in fetal guinea pig hearts and brains.

The aim of this study is to quantify the effect of intrauterine hypoxia (HPX) and the role of nitric oxide (NO) on the apoptotic enzyme, caspase 3, and DNA fragmentation in fetal heart and brain. Hypoxia and NO are important regulators of apoptosis, although this has been little studied in the fetal organs. We investigated the effect of intrauterine HPX on apoptosis and the role of NO in both fetal hearts and brains. Pregnant guinea pigs were exposed to room temperature (N = 14) or 10.5% O₂ (N = 12) for 14 days prior to term (term = 65 days) and administered water or L-N6-(1-iminoethyl)-lysine (LNIL), an inducible nitric oxide synthase (iNOS) inhibitor, for 10 days. Fetal hearts and brains were excised from anesthetized near-term fetuses for study. Chronic HPX decreased pro- and active caspase 3, caspase 3 activity, and DNA fragmentation levels in fetal hearts compared with normoxic controls. L-N6-(1-iminoethyl)-lysine prevented the HPX-induced decrease in caspase 3 activity but did not alter DNA fragmentation levels. In contrast, chronic HPX increased both apoptotic indices in fetal brains, which were inhibited by LNIL. Thus, the effect of HPX on apoptosis differs between fetal organs, and NO may play an important role in modulating these effects.

The Impact of Hypoxia on Cells, Mice, and Men

The Impact of Hypoxia on Cells, Mice, and Men

Novel Role for Non-muscle Myosin Light Chain Kinase (MLCK) in Hyperoxia-induced Recruitment of Cytoskeletal Proteins, NADPH Oxidase Activation, and Reactive Oxygen Species Generation in Lung Endothelium

We recently demonstrated that hyperoxia (HO) activates lung endothelial cell NADPH oxidase and generates reactive oxygen species (ROS)/superoxide via Src-dependent tyrosine phosphorylation of p47(phox) and cortactin. Here, we demonstrate that the non-muscle ~214-kDa myosin light chain (MLC) kinase (nmMLCK) modulates the interaction between cortactin and p47(phox) that plays a role in the assembly and activation of endothelial NADPH oxidase. Overexpression of FLAG-tagged wild type MLCK in human pulmonary artery endothelial cells enhanced interaction and co-localization between cortactin and p47(phox) at the cell periphery and ROS production, whereas abrogation of MLCK using specific siRNA significantly inhibited the above. Furthermore, HO stimulated phosphorylation of MLC and recruitment of phosphorylated and non-phosphorylated cortactin, MLC, Src, and p47(phox) to caveolin-enriched microdomains (CEM), whereas silencing nmMLCK with siRNA blocked recruitment of these components to CEM and ROS generation. Exposure of nmMLCK(-/-) null mice to HO (72 h) reduced ROS production, lung inflammation, and pulmonary leak compared with control mice. These results suggest a novel role for nmMLCK in hyperoxia-induced recruitment of cytoskeletal proteins and NADPH oxidase components to CEM, ROS production, and lung injury.

N-methyl-D-aspartate receptor subtype 3A promotes apoptosis in developing mouse brain exposed to hyperoxia.

In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyl-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling (TUNEL)/neuron-specific nuclear protein (NeuN) and 5-bromo-2′-deoxyuridine (BrdU)/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL+/NeuN+ and BrdU+/NeuN+ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.

Effects of Matrigel on expression of focal adhesion kinase and on proliferation and apoptosis of alveolar epithelial cell II of premature rat exposed to hyperoxia

To investigate the effects of Matrigel on expression of focal adhesion kinase and on proliferation and apoptosis of alveolar epithelial cell II of premature rat exposed to hyperoxia. The primary premature rat AECII (gestation 19 d) were cultured in vitro. For establishing hyperoxia-exposed cell model, purified AECII were cultured for 12 hours after culture flasks were filled with 95% oxygen-5% CO2 at 5 L/min, and then sealed for 12 hours. DNA content, phosphor and total protein of FAK were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting respectively after 12 hours of air or hyperoxia exposure in the presence or absence of Matrigel. To investigate the relationship between FAK activated and proliferation or apoptosis of type II alveolar epithelial cells, levels of proliferation and apoptosis of AECII were measured by immunohistochemical assay of proliferating cell nuclear antigen (PCNA) and TUNEL method respectively. FAK and FAK-Tyr(397) activity of AECII on Matrigel-coated substrate increased: compared with air group, the expression of PCNA decreased and apoptotic index increased markedly in hyperoxia group (0.1498 ± 0.009 vs. 0.0953 ± 0.006, P < 0.05; 1.232 ± 0.6 vs. 13.40 ± 3.2, P < 0.01), but the expression of PCNA of AECII on Matrigel-coated substrate increased significantly (0.1498 ± 0.009 vs. 0.1921 ± 0.008, P < 0.01) and apoptotic index did not change. The expression of PCNA increased significantly (0.0953 ± 0.006 vs. 0.1125 ± 0.012, P < 0.05) and apoptotic index decreased markedly in hyperoxia + Matrigel group as compared with hyperoxia group (13.40 ± 3.2 vs. 7.641 ± 1.6, P < 0.05). Hyperoxia decreased the level of FAK and FAK-Tyr(397) in AECII, which may be a contributory mechanism of impaired proliferation and apoptosis of AECII in hyperoxia induced lung injury in premature rat. Matrigel could inhibit apoptosis and promote proliferation of AECII resulted from hyperoxia in vitro. Matrigel may play a protective role in hyperoxia-induced lung injury partly due to activated FAK.

Hyperoxia inhibits growth of type II alveolar epithelial cells

Objective To investigate the effect of hyperoxia on growth of type Ⅱ alveolar epithelial cells (AECⅡ). Methods Lungs of fetal rats at 19 days of pregnancy were collected,and AEC Ⅱ was isolated and cultured by differential adherence method.Cells were randomly divided into air group and hyperoxia group.In air group,cells were cultured in 5％ CO2 incubator.And cells in hyperoxia group were cultured in 5％ CO2+95％ O2 incubator.The growth,activity,cell cycle,cell apoptosis of AEC Ⅱ were observed at 2,4,6 and 8 days of culture.The interaction between different time and groups were analyzed by ANOVA of factorial design.Comparison of means was done by two-sample independent t test and one-way analysis of variance.Bonferroni correction was used during the comparisons. Results (1) Cell growth situation:in hyperoxia group,cell number was decreased from2 hto 8 h [(7.29±0.43)×105/ml,(2.68±0.37)×105/ml,(0.23±0.10)×105/ml and (0.00±0.00) × 105/ml],and lower than those in air group [(10.41 ± 0.24) × 105/ml,(27.90±1.91) × 105/ml,(27.12±0.85) ×105/ml and (26.29±1.59) × 105/ml](t=10.992,38.912,94.166and 49.696,P=0.000 respectively). (2) Cell activity:the living cells ratio in hyperoxia group at 2 d[(79.00±0.71) ％],4 d [(52.80±1.14)％] and 6 d [(31.60±1.52)％] was lower than those [(97.00±0.71)％,(97.20±0.84)％ and (95.00±0.71)％] ir air group (t=31.213,70.519 and 84.722,P=0.000 respectively).(3) Cell cycle:the cell ratios of G1 phase and S phase in hyperoxia group at day 4 [(66.82±1.20) ％ and (27.31±1.16) ％] and day 6 [(70.22±1.27) ％ and (30.31±1.40) ％] were significantly higher than that at day 2 and that in air group (P＜0.05 respectively).(4) Cell apoptosis:in hyperoxia group,the cell ratio of Annexin-V+/PI- subgroup at 4 h was the highest [(23.89 ± 0.52)％],followed by those at day 2 and 6 [(21.32 ± 0.43)％ and (1.47 ±0.61)％].While the cell ratio of Annexin-V+/PI+ was the highest at 6 h [(53.92± 1.64)％],followed by those at 4 h and 2 h [(45.03±1.01)％ and (12.17±0.60)％],which were all different with those in air group(P＜0.05 respectively). Conclusions Hyperoxia might inhibit cell activity and cell cycle of AEC Ⅱ and promote apoptosis. Key words: Hyperoxia; Pulmonary alveoli; Epithelial cells; Cell growth processes; Apoptosis

Dynamic changes of ERK1/2 protein in lung fibroblasts of newborn rats with hyperoxia-induced chronic lung disease

Objective To investigate dynamic changes of extracellular signal regulated protein kinase (ERK) 1/2 in lung fibroblast of newborn rats with chronic lung disease (CLD) caused by hyperoxia.Methods Full-term newborn rats were randomly divided into two groups:air-exposed group and hyperoxia - exposed with 90％ oxygen group.Rats were sacrificed separately 3 d,7 d and 14 days after exposure to air or 90％ oxygen. Then lung fibroblasts of rats were isolated and primarily cultured. By using Immunocystochemistry,Western-blot and RT-PCR methods,the levels of ERK1/2 protein and expressions of ERK1/2 mRNA were measured. Results The levels of p-ERK1/2 protein in lung fibroblast in the hyperoxia group were significant higher on the 7th day and 14th day after exposure to 90％ oxygen compared with those in the air-exposed group (P ＜0.01 ).And the levels of total ERK1/2 protein and expressions of ERK1/2 mRNA did not change noticeably and were not significantly different between two groups (P ＞0.05 ).Conclusions The activation of phosphorated ERK1/2 may lead to lung fibrosis caused by hyperoxia in newborn rats. Key words: Hyperoxia; Newborn rat; Lung fibroblast; Extracellular signal regulated protein kinase

South Teton, Hypoxia

South Teton, Hypoxia

Risk factors of bronchopulmonary dysplasia in very low birth weight infants

Objective To investigate the risk factors of bronchopulmonary dysplasia(BPD)in very low birth weight infant.Methods The clinical data of 49 very low birth weight infants in our NICU from Sep 2006 to Sep 2009 were reviewed,and divided into BPD group(n =15)and without BPD group(n =34).The risk factors of BPD were analysed.Results Compared with the infants without BPD,there were significant differences in gestational age[(29.30 ± 1.48)week vs(30.54 ± 1.60)week],hospital-acquired infection(9 cases vs 10 cases),intrauterine infection(9 cases vs 8 cases),the time for continuous positive airway pressure(CPAP)[(12.47 ± 5.83)d vs(4.24 ± 4.19)d],the time for hyperoxia[(1.47 ± 1.41)d vs (0.18 ±0.63)d],patent ductus arteriosus(5 cases vs 1 cases)(P＜0.05).Logistic regression revealed that intrauterine infection and the time for CPAP were independent risk factors of BPD(P ＜0.05).Conclusion Prophylaxis of intrauterine infection may decrease the mortality and severity of BPD.The prolonged time for CPAP may predict the risk of BPD. Key words: Very low birth weight infant; Bronchopulmonary dysplasia; Risk factors; Infant, newborn

Changes in heart rate recovery index after a programme of strength/endurance training in hypoxia

ObjectiveTo determine whether twelve sessions of resistance training on lower limbs at simulated altitude (2500m) were efficient to elicit an improvement in heart rate recovery index in the first 3min of recovery after a maximal jump test. Materials and methodsTwelve young physically active subjects were divided in two balanced groups for training in hypoxia (HYP) and normal oxygen (NOR). The subjects were assigned to each group based on previous test results in the 60s counter-movement jump test (CMJ60). ResultsBoth groups performed identical strength training (volume, intensity, character and effort conditions) on the lower limbs (squats, half-squats and jumps) for 4 weeks. Both groups improved the measured parameters in all cases. We analyzed the time course of heart rate during the CMJ60 test and the subsequent 3min recovery period. HYP group (n=5) improved the heart rate recovery index as compared to NOR group (Student's t-test) at minute 2 (P=0.03) and minute 3 (P=0.05). ConclusionsWe conclude that a protocol of resistance training on lower limbs (12 sessions in 4 weeks) at a simulated altitude could improve heart rate recovery index compared to the same training performed at sea level.

Effects of hypoxia on epididymal sperm parameters and protective role of ibuprofen and melatonin.

Hypobaric hypoxia is of interest due to an increase of human populations working at high altitude. Testicular damage is related to the physiological response (neoangiogenesis) to increased intrascrotal blood flow as temperature rises. Hypoxia is a stress factor with overproduction of reactive oxygen species (ROS). The effect of hypoxia in mice reproductive parameters is analyzed. Animals were exposed to simulated hypoxia of 4,200 meters above sea level (m.a.s.l.) in a chamber for 33.2 days, both to continuous (HH) or intermittent hypoxia (HI) with an intermittency period of 4 days hypoxia /4 days normoxia (500 m.a.s.l.). The anti-inflammatory drug Ibuprofen was administered to a group of mice to control vasodilation and increased blood flow. Melatonin was administered to another group of mice as a potent ROS scavenger. Animals in both HH and HI exposure were compared to normoxic non-treated controls. There was a hematological response in hypoxia, with an increase in hematocrit and reticulocytosis. There was also increased teratozoospermia. This damage was more pronounced in HH than HI, suggesting that alternating normoxic periods permits compensation for the effects of hypoxia. In both hypoxia systems, the level of lipoperoxidation and the instability of DNA increased. In HH, there was a reduction of teratozoospermia in melatonin-treated mice. Ibuprofen presented a protective effect on the same parameters as melatonin with both HI and HH. The quality of sperm DNA, fragmentation, unpacking and DNA stability diminished. In conclusion, reproductive damage elicited by HH or HI was partially ameliorated by simultaneous treatment with antiflogistic and/or antioxidant agents.

P16 promoter methylation in premature rats with chronic lung disease induced by hyperoxia

Objective To investigate p16 promoter methylation in premature rats with chronic lung disease induced by hyperoxia. Methods Eighty premature Wistar rats were randomly divided into two groups: hyperoxia group (fraction of inspiratory oxygen) 0. 90 and control group (fraction of inspiratory oxygen 0. 21), 40 rats for each group. Semi-nested methylation specific polymerase chain reaction and methylation specific polymerase chain reaction were applied respectively to detect p16 promoter methylation in lung tissues. Additionally, p16 mRNA and protein expressions in lung tissue were detected by reverse transcription- polymerase chain reaction, Western blot and immunohistochemistry method. Results The methylation was not found in control group by seminested methylation specific polymerase chain reaction and methylation specific polymerase chain reaction, while was found in different aged rats of the hyperoxia group. The methylation detection rate was higher by using the semi-nested methylation-specific polymerase chain reaction (52.5%, 21/40) than that by methylation specific polymerase chain reaction (42.5%, 17/40) in the hyperoxia group,but there was no statistically significant difference between the two methods. The p16 mRNA in the hyperoxia group were significantly lower than in the control group at day 7, 14 and 21(1.73 ± 0.40 vs 2.11±0. 37,1.29±0. 19 vs 1.60±0. 27,0. 95±0.25 vs 1.72±0. 34, t=2.19, 2.95 and 10. 43,P＜0. 05). The p16 protein expressions by western blot in the hyperoxia group were significantly lower than in the control group at day 7, 14 and 21 also (88. 1±8. 7 vs 95.0±4.1,65.7±4.5 vs 83. 5±13.6 and 50.4±4.9 vs 86.7±11.9, t=2.27,3.95 and 13.40,P＜0.05). The expression of p16 mRNA (1.06±0.61) and protein (62.32±25.65) in lung tissues of rats with methylation was lower than that without methylation (1.63±0.62 and 94.93±22.21, respectively) (t=2.95, OR=0. 86;t=4.28, OR=0. 85,P＜0.01, respectively). Conclusions Exposure to hyperoxia might induce p16 promoter methylation in lung tissues in premature rats. Methylation risk increases as exposure time extends. p16 promoter methylation induced by hyperoxia might participate in the mechanism of lowering p16 mRNA and protein expression, but might not result in p16 gene silence. Key words: Hyperoxia; Lung diseases; Genes, p16; Promoter regions ( genetics ) ; Methylation; Infant, premature; Rats

Protection of hyperoxia-induced lung injury by granulocyte-macrophage colony-stimulating factor via RAGE-NF-κB signaling pathway in newborn rats

To explore the effects of granulocyte-macrophage colony-stimulating factor (GMCSF) on hyperoxia exposure lung injury in newborn rats and elucidate its protective mechanism of operating via the signaling pathway of advanced glycation end products (RAGE)-NF-κB. Twenty-four 3-day-old SD rats from 3 litters were randomly divided into 3 groups. They were hyperoxia exposure plus GMCSF group (group A), hyperoxia exposure group (group B) and air exposure group (group C). The rats from groups A and B were placed in a sealed Plexiglas chamber with a minimal in-and-outflow, providing 6 - 7 exchanges per hour of chamber volume and maintaining O(2) levels above 95%. While the rats in group C only were exposed to air simultaneously. The rats in group A received subcutaneous injections of recombinant murine GMCSF (9 µg/kg) during hyperoxia exposure at 24 h, 72 h and 120 h respectively. And the rats in groups B and C received subcutaneous injections of saline vehicle alone at the same time point. Seven days later, all were sacrificed and immunohistochemistry was employed to assess the expression of RAGE in lung tissue. The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) and serum samples were detected by ELISA (enzyme-linked immunosorbent assay). The RAGE mRNA and NF-κB mRNA in tissue homogenates were detected by RT-PCR while RAGE and NF-κB by Western blot. Also the values of lung damage score were calculated with microscopic histology. The value of lung damage score in group C, B and A was 0.46 ± 0.20, 3.06 ± 0.33 and 2.31 ± 0.56 respectively, there was significantly difference among three groups (P = 0.000). The expression of RAGE mRNA and protein in three groups were 0.14 ± 0.02, 0.34 ± 0.06, 0.28 ± 0.04 and 0.30 ± 0.04, 0.76 ± 0.11, 0.55 ± 0.08 respectively. There were both significantly differences among three groups (P = 0.000, P = 0.000). The expression of NF-κB mRNA and protein in three groups were 0.41 ± 0.21, 0.90 ± 0.36, 0.69 ± 0.30 and 0.41 ± 0.26, 0.96 ± 0.43, 0.77 ± 0.33 respectively, there were both significantly difference among three groups (P = 0.000, P = 0.017). The level of TNF-α in BALF was 76 ± 10, 224 ± 42 and 143 ± 24 respectively, there was significantly difference among three groups (P = 0.000). All indicators above in group B and group A were significantly more than those in group C (all P < 0.05), while these indicators in group A were lower than those in group B. But there was no difference in the level of TNF-α of serum among three groups (P > 0.05). GMCSF may protect hyperoxia-induced lung injury via down-regulating the signaling pathway of RAGE-NF-κB.

Clinical effect of Liushen mixture combined with hyperoxia solution to treat pressure sores of patients with advanced cancer

Objective To study the clinical effect of Liushen mixture combined with hyperoxia solution to treat the pressure sores of advanced cancer patients. Methods 43 cases of advanced cancer patients with pressure sores were randomly divided into the experimental group (21 patients)and the control group (22 patients). All patients received conventional care after debridement, the experimental group was treated by 30 to 60 Liushen pills grinded into powder reconciled with 3～8 ml 2% lidocaine to cover the affected area as external fomentation by sterile gauze which was soaked by hyperoxia solution, fixed with cling film,regular replacement The control group was coated with silver sulfadiazine sterile gauze and regular replacement. The cure rate, efficiency rate, and healing time of pressure sores of the two groups were observed respectively. Results In the experimental group the cure rate and efficiency rate were respectively 76.19% and 90.48%, and the cure rate and efficiency rate of the control group were 45.45% and 63.64%, the difference was statistically significant. In the experimental group the phase Ⅲ pressure sores' healing time was ( 13.60± 4.92)days, the healing time of the control group was(20.76 ± 5.51 )days, the difference was statistically significant. Conclusions Liushen pills and lidocaine mixture combined with hyperoxia solution to treat the pressure sores of advanced cancer patients have significant effect and are worthy of clinical application. Key words: Liushen pill; Lidocaine; Hyperoxia solution; Advanced cancer; Pressure sore

A clinical profile of 103 patients with secondary movement disorders: correlation of etiology with phenomenology

Studying patients with secondary movement disorders (SMD) provides a unique opportunity to determine the correlation between the etiology and phenomenology of movement disorders. This was a prospective study of 103 patients (43 women, 60 men; age=28.7±17.3 years; range=2-70 years) with SMD, in a tertiary hospital over 4 years. The mean age of onset of SMD was 24.3±19.7 years, and duration of symptoms was 4.3±7.1 years (42 days to 40 years). Patients with pure tremor, pure dystonia (DYS), or a combination of tremor with dystonia had longest latency (10.9-18.5 months), whereas those with parkinsonism (PAR) and hemiballismus (HMB) had shorter latency (2.7-3.0 weeks). Pure dystonia was most prevalent (30.1%) followed by dystonia plus (13.6%), tremor (12.6%), PAR (11.7%), HMB (8.7%), mixed SMD (7.8%), tremor with dystonia (6.8%), myoclonus (5.8%), and chorea (2.9%). In approximately 60% of patients, the underlying etiologies were vascular (VAS), infections, and space-occupying lesions (SOL), and 25% had SMD following trauma or hypoxia (HYP). With reference to specific etiologies, the most frequent SMDs were tremor following SOL (46%), post-traumatic syndromes (25%), dystonia following HYP (56%), VAS lesions (50%), and infections (28%). With reference to specific SMDs, the most common etiologies were VAS for dystonia (39%), SOL for tremor (67%), and PAR (31%), and both SOL and trauma (37.5% each) for tremor with dystonia. Our study highlights the spectrum of SMDs and the lack of correlation between types of SMDs and underlying etiologies. Preventable causes such as infections, HYP, trauma, and kernicterus still play a major role in pathogenesis of SMD.

The dynamic study of total antioxidative capacity and malondialdehyde in the liver of newborn rats induced by hyperoxia

Objective To determine the levels of total antioxidative capacity(TAOC) and malondialdehyde(MDA) in liver exposed to hyperoxia,and to explore whether oxygen inhalation could cause liver injury in newborn rats.Methods Sixty-four newborn rats which were less than 12-hour-old were enrolled in this study.The rats were randomly divided into hyperoxia group(FiO2=0.85,n=32) and control group(air,n=32).Eight rats in each group were randomly sacrificed to obtain liver tissues at 1d,3d,7d and 14d.The TAOC of liver homogenates was detected by chemical colorimetry,and the MDA level of liver homogenates was measured by thiobarbituric acid test.Results In the hyperoxia group,TAOC in liver increased on the 1st day[(3.60±0.28)U/mg prot vs(3.39±0.19)U/mg prot,P<0.05];TAOC began to decreased on the 3rd day,and significantly lower than that of control group on the 14th day [(3.10±0.15)U/mg prot vs (3.56±0.14)U/mg prot,P<0.01].In the hyperoxia group,the MDA level increased on the 3rd day[(3.58±0.11)nmol/mg prot vs(2.82±0.14)nmol/mg prot,P<0.01],and reached a peak on the 7th day[(3.58 ±0.11)nmol/mg prot vs(2.82±0.14)nmol/mg prot,P<0.01],then decreased but still remained higher than control group on the 14th day [(2.92±0.18)nmol/mg prot vs(2.77 ±0.09)nmol/mg prot,P<0.01].Conclusion Too more MDA in liver and TAOC decrease may cause liver injury in newborn rats exposed to hyperoxia.With the oxygen inhalation time prolonging,the liver injury aggravation. Key words: Hyperoxia; Liver injury; Rat newborn

The high-risk factors for bronchopulmonary dysplasia in premature infants of mechanical ventilation

Objective To explore the incidence rate and high-risk factors for bronchopulmonary dysplasia(BPD) in premature infants of mechanical ventilation.Methods From Jan 2008 to Dec 2009,196 very low birth weight infants with gestational age less than 32 weeks in our NICU were enrolled in the study.61 cases had the histories of mechanical ventilation.The clinical materials of 21 cases with BPD were compared to 41 cases without BPD in retrospective analysis.Results The total incidence of BPD in the very low birth weight infants with gestational age less than 32 weeks was 10.7%,and 34.4% in those infants with mechanical ventilation.The gestational age and birth weight of BPD group were lower than those without BPD,and the rates of premature rupture of fetal membrane and complicated neonatal respiratory distress syndrome (NRDS),postnatal infection,with long time intravenous nutrition in BPD group were higher than those without BPO control (P 0.05).Peak inspiratory pressure (PIP),the time of mechanical ventilation and oxygen administration were different significantly between two groups (P<0.05).NRDS,postnatal infection,the duration of ventilation,and hyperoxia were the risk factors for BPD,and the regression coefficient were 3.683,1.541,1.188 and 1.647.Conclusion Preventing premature,low birth weight,NRDS,shortening the duration of high peak inspiratory pressure and hyperoxia with mechanical ventilation and the use of the parenteral nutrition,managing the infection of the prenatal and postnatal are the key points of preventing BPD. Key words: Mechanical ventilation; Premature infant; Bronchopulmonary dysplasia; Risk factors

Hyperoxia and Apoptosis

Hyperoxia and Apoptosis

Purinergic receptors of the nucleus of the solitary tract are involved in the ventilatory response to hypoxia

Hypoxia (HYP) triggers many cardiorespiratory responses, including increased pulmonary ventilation (VE), which depends on brainstem areas including the nucleus of the solitary tract (NTS). Studies have demonstrated the involvement of purinergic receptors of the surface of the medulla in the cardiorespiratory responses induced by HYP. Thus, we investigated the involvement of purinergic receptors of the NTS on cardiorespiratory responses induced by HYP in awake rats. Male Holtzman rats (280–320 g, n = 6) with stainless steel guide-cannulas implanted in the NTS were used. We recorded mean arterial pressure (MAP), heart rate (HR) and VE before and after bilateral injections of saline (SAL) or suramin (SUR, a non-selective purinergic receptor antagonist) into the NTS in normoxia (NORM, 21% O2) or HYP (7% O2). HYP reduced MAP (100 ± 11 mmHg, vs. NORM 121 ± 3 mmHg, p <0.05) and increased VE (1521 ± 376 ml/min/kg, vs. NORM 730 ± 227 ml/min/kg, p<0.05) without changing HR (388 bpm ± 32, vs. NORM 384 ± 6 bpm). Bilateral injections of SUR (2 nmol/100 nl) into the NTS reduced HYP-induced hyperventilation (505 ± 208 ml/min/kg, vs. SAL 1508 ± 376 ml/min/kg, p<0.05) without changing MAP (Δ −5 ± 2 mmHg, vs. SAL −7 ± 10 mmHg) and HR (Δ 18 ± 24 bpm, vs. SAL 9 ± 12 bpm). Bilateral injections of SUR into the NTS did not change MAP, HR and VE in NORM. The results suggest that activation of purinergic receptors in the NTS facilitate HYP-induced hyperventilation.

ERRα rescues histone deacetylation‐mediated down‐regulation of PGC‐1α expression in hypoxia

ERRα rescues histone deacetylation‐mediated down‐regulation of PGC‐1α expression in hypoxia