The effect of oxygen therapy on brain damage and cerebral pO(2) in transient focal cerebral ischemia in the rat

We examined the effect of hyperbaric oxygen (HBO) and normobaric oxygen (NBO) on neurologic damage and brain oxygenation before and after focal cerebral ischemia in rats. A middle cerebral artery occlusion (MCAO)/reperfusion rat model was used. The rats were sacrificed 22 h after reperfusion, and the infarct volume was evaluated. In study A, HBO (2.0 ATA), NBO (100% oxygen) and normobaric air (NBA) were each administered for 60 min in five different rat groups. The sizes of the infarcts after HBO and NBO applied during ischemia were 8.8 +/- 2.8% and 22.8 +/- 3.7% respectively of the ipsilateral non-occluded hemisphere. The infarct size after HBO applied during ischemia was statistically smaller than for NBO and NBA exposure (p < 0.01). In study B, cerebral pO(2) was measured before and after MCAO and HBO exposure (2.0 ATA for 60 min) in six rats using electron paramagnetic resonance (EPR) oximetry. The pO(2) in the ischemic hemisphere fell markedly following ischemia, while the pO(2) in the contralateral hemisphere remained within the normal range. Measurements of the pO(2) performed minutes after HBO exposure did not show an increase in the ischemic or normal hemispheres. The mean relative infarct size was consistent with the changes observed in study A. These data confirm the neuroprotective effects of HBO in cerebral ischemia and indicate that in vivo EPR oximetry can be an effective method to monitor the cerebral oxygenation after oxygen therapy for ischemic stroke. The ability to measure the pO(2) in several sites provides important information that should help to optimize the design of hyperoxic therapies for stroke.     

Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery

OBJECTIVE: Hyperbaric oxygen (HBO) increases oxygen supply to anoxic areas. To examine the therapeutic effect of HBO on ischemic stroke, we measured infarct volume as well as cerebral blood flow (CBF), oxygen supply, and lipid peroxidation in the ischemic periphery. DESIGN: Prospective experimental study in rats. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty-eight adult rats. INTERVENTION: The rats were anesthetized (1% halothane) and intubated. Focal ischemia was induced by ligating the right middle cerebral and right common carotid arteries. Nineteen animals were exposed to 2 hrs of HBO (100% oxygen, 3 atmospheres absolute), initiated 10 mins after the onset of ischemia. The remaining animals were kept at ambient pressure and used as controls. MEASUREMENTS AND MAIN RESULTS: At the initiation of ischemia, CBF measured by a laser-Doppler flow probe placed in the ischemic periphery was reduced to 47%+/-11% and 51%+/-15% of normal levels in animals exposed or not to HBO, respectively. These altered values were not affected further by administration of HBO and remained stable throughout a 2-hr observation period. Arterial oxygen pressure and content were significantly increased to 1571+/-130 torr (209.41+/-17.32 kPa; p < .0001) and 1.03+/-0.04 mmol/dL (p < 0.0001), respectively, in HBO-treated animals compared with nontreated animals (139+/-14 torr [18.53+/-1.87 kPa] and 0.86+/-0.04 mmol/dL, respectively). The calculated increase in the oxygen supply to the ischemic periphery was 20%. The infarct volume of HBO-treated animals measured 24 hrs after the onset of focal cerebral ischemia was significantly reduced by 18% (HBO-treated, 132+/-13 mm3 vs. nontreated, 161+/-29 mm3; p = .02). Lipid peroxidation was unchanged after 120 mins of HBO administration in the cerebral cortex where the laser-Doppler flow probe was placed. CONCLUSIONS: HBO at 3 atmospheres absolute reduced infarct volume by increasing oxygen supply to the ischemic periphery without aggravating lipid peroxidation, suggesting that HBO can be useful in treating stroke victims.     

A single exposure to hyperbaric oxygen does not cause oxidative stress in isolated platelets: no effect on superoxide dismutase, catalase, or cellular ATP

OBJECTIVES: The aim of the study was to investigate whether a single hyperbaric oxygen exposure causes oxidative stress in isolated platelets. DESIGN AND METHODS: Isolated horse platelets were exposed to 100% oxygen at 2.2 atmospheres, or 100% oxygen under normobaric conditions, or air under normobaric conditions for 90 min. RESULTS: There were no differences in platelet SOD activity between conditions, but there was a rise in SOD in all cases after 24 h (in control platelets at 24 h, SOD was 11.9 +/- 1.9 nmol/min/mg protein compared to initial background levels of 8.2 +/- 1.9 nmol/min/mg protein) (P < 0.05). Neither platelet catalase activity nor platelet GSH concentration changed over time, nor between conditions (catalase activity remained at around 12 units/mg protein, and GSH at around 1.58 nmol/mg protein). CONCLUSIONS: These data suggest that a single HBO exposure has no detrimental effect on platelet biochemistry, and does not cause overt oxidative stress in vitro.     

Effect of hyperbaric oxygen on flow-mediated vasodilation: an ultrasound study

OBJECTIVE: The purpose of this study was to investigate the effect of hyperbaric oxygen (HBO) treatment on flow-mediated vasodilation (FMD) by ultrasound examination. METHODS: We studied 14 young patients without cardiovascular problems who underwent HBO treatment. The indications for HBO treatment were osteomyelitis (n = 8), Crohn disease (n = 2), perianal abscesses (n = 2), lingual artery embolization (n = 1), and aseptic necrosis (n = 1). The ultrasound evaluation for FMD was performed before HBO treatment, after 1 session of HBO treatment, and after 10 sessions of HBO treatment. The right brachial artery FMD response was evaluated by the mean of the baseline right brachial artery diameter, absolute change in the diameter before and after cuff inflation/deflation, and percent change in the diameter. RESULTS: Statistical analysis showed a significant change in the preinflation right brachial artery diameter before (mean +/- SD, 3.6 +/- 0.54 mm) and after (3.76 +/- 0.56 mm) 10 sessions of HBO treatment (P < .05). The absolute changes in the right brachial artery diameter before and after cuff inflation/deflation (0.36 +/- 0.2 mm before HBO treatment, 0.37 +/- 0.22 mm after 1 session of HBO treatment, and 0.38 +/- 0.21 mm after 10 sessions) and percent change in FMD (10% +/- 5.8% before HBO treatment, 10.6% +/- 7.5% after 1 session of HBO treatment, and 10.6% +/- 7.7% after 10 sessions) after induction of a hyperemic response by cuff inflation were not statistically significant (P > .05). CONCLUSIONS: Hyperbaric oxygen treatment did not have an immediate effect on FMD (absolute change in the right brachial artery diameter after cuff inflation/deflation); however, the right brachial artery diameter increased after 10 sessions of HBO treatment. This may suggest chronic stress on the vascular endothelium after HBO.     

Hyperbaric Oxygen Does Not Prevent Neurologic Sequelae after Carbon Monoxide Poisoning

Delayed neurologic sequelae occur in up to 40% of severe carbon monoxide (CO) poisonings. Conflicting clinical data support the efficacy of hyperbaric oxygen (HBO) therapy in the acute treatment of CO poisoning. OBJECTIVE: To determine whether oxygen therapy reduces neurologic sequelae after CO poisoning in mice. METHODS: Male Swiss-Webster mice were exposed to CO at 1,000 ppm for 40 minutes and then 50,000 ppm until loss of consciousness (LOC) (4-9 additional minutes). Total time of both phases of CO exposure was 40-49 minutes. Treatment included HBO with 3 atmospheres (ATA) 100% oxygen, normobaric oxygen (NBO) with 1 ATA 100% oxygen, or ambient air 15 minutes after LOC. All animals underwent passive avoidance training and memory was assessed by measuring step-down latency (SDL) and step-up latency (SUL) seven days following CO exposure. RESULTS: Carbon monoxide poisoning induced significant memory deficits (SDL(CO) = 156 sec; SUL(CO) = 75%) compared with nonpoisoned (NP) animals (SDL(NP) = 272 sec; SUL(NP) = 100%). Both HBO and NBO did not prevent these neurologic sequelae. Furthermore, no significant neurobehavioral differences were found between HBO and NBO. Histologic examination of the CA1 layer of the hippocampus for pyknotic cells showed significant damage from CO in the air-treated animals (9.6%) but not in the nonpoisoned animals (3.8%). No significant neuroprotection was seen histologically with NBO and HBO compared with ambient air. CONCLUSIONS: These results suggest that HBO is not effective in preventing neurologic sequelae in mice and that there is no benefit of HBO over NBO following severe CO neurotoxicity.     

S100B protein in conscious carbon monoxide-poisoned rats treated with normobaric or hyperbaric oxygen

OBJECTIVE: To evaluate S100B, an astroglial structural protein, during normobaric and hyperbaric oxygen therapy of conscious carbon monoxide (CO)-poisoned rats. So far, the usefulness of hyperbaric oxygen therapy in conscious CO-poisoned patients has been shown with neuropsychological testing. The S100B protein has been demonstrated as a possible biochemical marker and prognostic parameter in CO-poisoned rats. DESIGN: Randomized, controlled interventional trial. SETTING: University laboratory. SUBJECTS:: Male Wistar rats weighing 254 +/- 14 g. INTERVENTIONS: The rats were exposed to a mixture of 3,000 ppm CO in air for 60 mins. After CO exposure, the first group of eight conscious rats was exposed to ambient air for 30 mins, the second group of six conscious rats was exposed to 100% normobaric oxygen for 30 mins, and the third group of six conscious rats was exposed to 100% hyperbaric oxygen at 3 bars for 30 mins. Blood samples were taken from the jugular vein just before CO exposure and immediately after oxygen therapy. The level of consciousness was evaluated at the end of exposure, and the survival rate was monitored for 14 days. The S100B concentrations were measured with a commercial immunoluminometric assay. MEASUREMENTS AND MAIN RESULTS: Analyses of differences in S100B levels between different kinds of therapy before and after treatment showed a global significant difference (p = .002). The post hoc test results showed that S100B levels after therapy of the first group treated with ambient air (0.16 +/- 0.07 microg/L) and the second group treated with normobaric oxygen (0.19 +/- 0.05 microg/L) were similar (p = .741), and both of them were significantly different, with much higher values of S100B levels after therapy, from the third group treated with hyperbaric oxygen (0.06 +/- 0.03 microg/L; p = .018 and p = .002, respectively). All the rats survived. CONCLUSIONS: S100B is elevated in conscious CO-poisoned rats left on ambient air or treated with normobaric oxygen, but not in conscious CO-poisoned rats treated with hyperbaric oxygen.     

高压氧治疗对海马区急性脑缺血再灌注损伤的远期疗效

目的探讨高压氧(hyperbaricoxygen,HBO)治疗对海马区急性脑缺血再灌注损伤的远期疗效。方法沙土鼠脑缺血20min后再灌注,同时应用24.52kPaHBO治疗,连续3d,停止治疗2d后,应用TUNEL标记神经元凋亡,观察HBO治疗停止后神经元凋亡的变化。结果24.52kPaHBO治疗停止2d后,海马神经元凋亡数比24.52kPaHBO治疗结束时显著减少(P<0.01),比单纯缺血再灌注5d组亦显著减少(P<0.01)。结论24.52kPaHBO治疗急性脑缺血损伤具有良好的疗效,未见“反跳”现象。     

Hyperbaric oxygen therapy given 30 minutes after spinal cord ischemia attenuates selective motor neuron death in rabbits

OBJECTIVE: Spinal cord ischemia sometimes causes paraplegia because the spinal motor neuron cells are vulnerable to ischemia. Although various protective remedies for spinal cord injury have been reported, there have been few established clinical methods. Although hyperbaric oxygen (HBO) has been used clinically as a treatment for ischemia, the reason for its effectiveness is still uncertain because sufficient experimental data are lacking. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Twenty-three Japanese white rabbits, weighing 2-3 kg. INTERVENTIONS: A modified rabbit spinal cord ischemia model of infrarenal aortic occlusion for 15 mins was employed. Rabbits were randomly assigned to four groups; the rabbits in group A did not undergo ischemic insults (n = 5). The rabbits in groups B and C underwent ischemic insult for 15 mins, followed by 1 hr of HBO treatment at 3 atm absolute with 100% oxygen at 30 mins (n = 6) or 6 hrs (n = 7) after reperfusion, respectively. The rabbits in group D underwent ischemic insult for 15 mins without HBO treatment (n = 5). MEASUREMENTS AND MAIN RESULTS: We observed neurologic functions for 14 days. The sections of the spinal cords were stained with hematoxylin and eosin, and the number of spinal motor neurons in ventral region was counted by light microscopy. All rabbits in groups A and B could stand, whereas all rabbits in groups C and D showed irreversible paraplegia on days 2 and 14 after reperfusion. Spinal motor neurons in ventral gray matter in groups C and D decreased significantly compared with those in groups A and B. CONCLUSIONS: HBO therapy shortly after ischemic insult had protective effects against ischemic spinal cord damage. However, delayed treatment with HBO did not change the prognosis.     

高压氧对脑缺血再灌注海马CA1区神经元凋亡的作用

目的研讨高压氧(HBO)对脑缺血再灌注损伤的疗效及其机制,为临床HBO治疗疾病提供理论依据。方法实验动物用沙土鼠20只,雌雄不限。采用随机数字法将实验动物分为正常对照组、缺血组、0.15MPaHBO治疗组、0.25MPaHBO治疗组、0.25MPa压力空气(hyper-baricair,HBA)对照组5组(n=4)。应用TUNEL检测技术,对沙土鼠前脑缺血20min后再灌注3d模型,用高压氧(hyperbaricoxygen,HBO)治疗连续3d,观察HBO作用下海马CA1区神经元凋亡变化。结果沙土鼠脑缺血再灌注3d后海马CA1区大量神经元凋亡犤(163±15)/mm2犦,HBO治疗组凋亡细胞数犤0.15MPaHBO治疗组为(99±12)/mm2,0.25MPaHBO治疗组为(73±11)/mm2犦明显减少(P<0.01),0.25MPa空气对照组凋亡细胞数为(151±13)/mm2,以0.25MPaHBO治疗组为佳。结论HBO治疗对海马神经元损伤有保护作用,减少神经元凋亡,为高压氧治疗缺血性损伤的疗效机制之一。     

Effect of hyperbaric oxygen on endotoxin-induced lung injury in rats

Oxygen therapy remains the main component of the ventilation strategy for treatment of patients with acute lung injury. Hyperbaric oxygen therapy (HBO(2)) is the intermittent administration of 100% oxygen at pressure greater than sea level and has been applied widely to alleviate a variety of hypoxia-related tissue injuries. The purpose of this study was to evaluate the effect of hyperbaric oxygen on acute lung injury induced by intratracheal spraying of lipopolysaccharide (LPS) in rats. Male Sprague-Dawley rats underwent implantation of a carotid artery catheter under general anesthesia. Aerosolized LPS was delivered twice into the lungs via intratracheal puncture. Animals were either breathing room air (n = 27) or subjected to hyperbaric oxygen (HBO(2)) exposure (n = 27) 1 h after LPS spraying. Acute lung injury was evaluated 5 h and 24 h later. Compared with the control group, intratracheal spraying of LPS caused profound hypoxemia, greater wet/dry weight ratio (W/D) of the lung (5.67 +/- 0.22 vs. 4.98 +/- 0.19), and higher protein concentration (1706 +/- 168 vs. 200 +/- 90 mg/L) and LDH activity (129 +/- 30 vs. 46 +/- 15, mAbs/min) in bronchoalveolar lavage (BAL) fluid. Intratracheal spraying of LPS also caused significant WBC sequestration in the lung tissue. HBO2 treatment significantly reverted hypoxemia, reduced lung injury measures evaluated at 5 and 24 h, and enhanced 24-h animal survival rate (chi = 5.08, P = 0.024). The malondialdehyde (MDA) concentrations in lung tissue and serum were both increased after LPS spraying. Neither single HBO(2) therapy nor five sequential daily treatments enhanced MDA production in lung tissue or serum. Our results suggested that hyperbaric oxygen might reduce acute lung injury caused by intratracheal spraying of LPS in rats. This treatment modality is not associated with enhancement of oxidative stress to the lung.     

Hyperbaric oxygen therapy accelerates neurologic recovery after 15-minute complete global cerebral ischemia in dogs.

BACKGROUND AND METHODS: Although hyperbaric oxygen therapy is clinically used for the treatment of several types of ischemic brain injury, few basic animal studies are available that provide a rationale for this therapy for complete global brain ischemia. Therefore, we investigated the effect of hyperbaric oxygen therapy on neurologic recovery after 15-min complete global cerebral ischemia in a canine model. Complete global ischemia was induced in 19 dogs by occlusion of the ascending aorta and the caval veins. Nine dogs were randomized to treatment with hyperbaric oxygenation (3 atmospheres absolute, 100% oxygen for 1 hr) at 3, 24, and 29 hrs after ischemia under spontaneous respiration, while the other ten dogs served as the control group without hyperbaric oxygen therapy (group C). Neurologic recovery was evaluated based on the electroencephalogram (EEG) activity score (1 = normal; 5 = isoelectric) and the neurologic recovery score (100 = normal; 0 = brain death) over a 14-day postischemic period. RESULTS: The survival rates were 3/10 (30%) in the control group vs. 7/9 (78%) in the group treated with hyperbaric oxygen (p < .05). Over the 14-day postischemic period, the best (lowest) EEG scores of each dog were significantly (1.7 +/- 0.2 vs. 2.9 +/- 0.3; mean +/- SE, p < .01) lower in the hyperbaric oxygen-treated group. The best neurologic recovery scores of each dog were significantly (69 +/- 6 vs. 48 +/- 5; mean +/- SE, p < .05) higher in the treated animals. The number of dogs that recovered to a neurologic recovery score of > 65 (assessed as a slight disability) were 1/10 in the control group and 6/9 in the group treated with hyperbaric oxygen (p < .02). CONCLUSIONS: Hyperbaric oxygen therapy performed in the early postischemic period accelerated neurologic recovery and improved the survival rate in dogs after 15-mins of complete global cerebral ischemia.     

短暂性全脑缺血再灌注大鼠经高压氧治疗后脑组织神经节苷脂的变化

背景:神经节苷脂是神经组织中含量丰富并可发挥神经保护作用的含唾液酸的鞘糖脂,在脑缺血或缺氧性疾患时有含量或组分的变化。目的:通过观察全脑缺血再灌注大鼠应用高压氧治疗后脑组织神经节苷脂的变化情况,探讨高压氧对缺血再灌注损伤治疗作用的可能途径。设计:随机-对照观察。单位:首都医科大学附属朝阳医院高压氧科和首都医科大学基础医学院生物化学与分子生物学系。材料:动物模型制作于2002-03/04在首都医科大学附属朝阳医院高压氧科(北京市重点实验室)完成,各项指标检测在首都医科大学基础医学院生物化学与分子生物学系完成。选择雌性SD大鼠54只,将大鼠随机分成9组,即假手术组、缺血再灌注6h,24h,48h,96h组及高压氧6h,24h,48h,96h组,每组6只。方法:除假手术组外,其余8组大鼠均建立脑缺血再灌注动物模型,按四动脉阻断法建立,缺血20min后再通。假手术组同样手术但不阻断动脉。将高压氧组大鼠置于实验舱内,纯氧洗舱5min,升压5min至0.1MPa后稳压,吸纯氧45min,减压10min。高压氧组大鼠在缺血再灌注3h后行高压氧处理1次,24h,48h及96h组在每天同一时间行高压氧处理1次。缺血再灌注组和假手术组处于常压空气环境中。再灌注组和高压氧处理组大鼠分别于再灌注6h,24h,48h及96h麻醉取全脑标本测定总神经节苷脂及各组分百分含量,神经节苷脂各组分以高效薄层层析法测定。主要观察指标:各组大鼠全脑组织神经节苷脂的总含量及其各组分的百分含量。结果:54只大鼠全部进入结果分析,无脱失。①高压氧24h及48h组总神经节苷脂均显著高于假手术组及相应缺血再灌注时相组(F=12.730,122.246,P<0.01),但缺血再灌注各时相组与假手术组相比,差异均无显著性意义(P>0.05)。②对缺血再灌注24h组大鼠GT1b相对含量显著低于假手术组(F=13.575,P<0.01),再灌注48h组GD1b及GM1分别低于假手术组(F=4.015,3.979,P<0.05),GM3于再灌注24h高于假手术组及其他时相组(F=21.450,P<0.01),并于再灌注96h反弹。③高压氧24h组GM1,GM3分别高于假手术组(F=3.970,21.450,P<0.05,<0.01),GD1a、GD1b和GT1b均低于假手术组(F=13.575,5.745,8.783,P<0.05～0.01),但GT1b明显高于缺血再灌注各相应时相组(F=8.783,P<0.05)。结论:大鼠短暂全脑缺血再灌注后可引起神经节苷脂总含量、GT1b,GD1b,GM1百分含量降低及GM3百分含量升高,其中提高脑组织神经节苷脂总量、GM1含量及加速GT1b的恢复可能为高压氧治疗改善缺血性脑损伤的作用途径,而GD1a,GD1b百分含量的下降有何作用尚不清楚。     

高压氧对重症中暑大鼠认知障碍的保护作用

目的研究高压氧（HBO）治疗对大鼠重症中暑脑损伤模型认知功能障碍的保护作用。 方法将60只雄性SD大鼠随机分为空白对照组（Control组,10只）、重症中暑组（HS组,10只）、重症中暑＋高压氧治疗组（HS＋HBO组,10只）、重症中暑＋高压空气对照组（HS＋HBA组,10只）、高压氧对照组（HBO组,10只）、高压空气对照组（HBA组,10只）,将HS组、HS＋HBO组、HS＋HBA组大鼠持续暴露于40℃热舱中,当核心体温达到42℃后取出复温,HS＋HBO组与HS＋HBA组复温30 min后分别给予HBO（2.5ATA,60 min）或高压空气（2.5ATA,60 min）处理,通过Morris水迷宫实验评估认知功能（航行距离和时间、目标象限航行时间百分比和通过次数）,并检测各组大脑海马组织病理、神经功能评分及病死率变化。 结果HS组大鼠水迷宫寻找平台潜伏期较Control组明显延长［（45.84±0.13）s vs （22.16±1.40）s,t=-2.4,P=0.04］,寻找平台航行距离延长［（815.70±36.80）cm vs （177.71±21.00）cm,t=-3.3,P=0.01］,通过次数［（1.90±0.16）次 vs （5.80±0.20）次,t=3.7,P=0.04］和目标象限航行时间百分比［（32.12±0.19）% vs （57.12±1.60）%,t=2.8,P=0.02］明显减少;HBO治疗缩短了寻找平台的潜伏期［（30.21±1.50）s］与航行距离［（165.58±7.04）cm］,增加了穿越次数［（4.40±0.18）次］和目标象限航行时间百分比［（41.87±1.17）%］;HBO改善了HS组大鼠海马组织病理损伤程度,降低了中暑后2 h、24 h神经功能评分［2 h：（7.70±0.42）分 vs （9.60±0.31）分,t=6.3,P=0.00;24 h：（3.90±0.20）分 vs （5.60±0.23）分,t=2.4,P=0.02］及病死率（20.0% vs 40.0%,P=0.08）,HS＋HBA组较HS组无明显改变,HBO组、HBA组较Control组无明显改变。 结论HBO可能是通过减轻重症中暑对海马的损伤来改善大鼠重症中暑模型的认知功能障碍。     

The effects of amifostine and dexamethasone on brain tissue lipid peroxidation during oxygen treatment of carbon monoxide-poisoned rats

The mechanisms of injury of, and methods of treating patients with, carbon monoxide (CO) poisoning are poorly understood. Besides the hypoxic degenerative effects of CO, reoxygenation injury may play an important role. Amifostine (Ami), which is most often used in radiotherapy for its tissue protective characteristics, may offer benefits. In this study, investigators evaluated the effectiveness of various treatments in a CO-poisoned rat model. A total of 36 Wistar rats were randomly assigned to 1 of 6 groups (n=6 each), including control and poisoned groups exposed to CO at 2000 ppm (v/v) for 1 h, followed by various 1-h treatments: group C (control), group CO-air (ambient air), group CO-NBO (normobaric 100% oxygen), group CO-HBO (hyperbaric oxygen with 3 atmospheres absolute [3 ATA]), group CO-NBO-Ami (normobaric oxygen with intraperitoneal [IP] injection of amifostine 250 mg/kg body weight [bw]), and group CO-70O (70% O₂ and 5% CO₂ with dexamethasone 10 mg/kg bw, IP). Blood gas analysis, carboxy-hemoglobin determination, brain tissue lipid peroxidation, and glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactate dehydrogenase (LDH), and creatine kinase (CK) activities were evaluated. Carboxyhemoglobin concentration in the air-treated group was 44±2%; it decreased to the control level with all oxygen treatments. Brain tissue GSH-Px and SOD measurements did not change. The activity of LDH in group CO-HBO and the activities of LDH and CKin group CO-70O were similar to those of group C. Lipid peroxides were high in ambient air and normobaric oxygen, but HBO, amifostine with oxygen, or 70% O₂ reduced these to control levels (P < .05).     

Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study

OBJECTIVE: To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers. RESEARCH DESIGN AND METHODS: From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline. RESULTS: HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group. CONCLUSIONS: In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.     

Peak expiratory flow at increased barometric pressure: comparison of peak flow meters and volumetric spirometer

Increasing numbers of patients are receiving hyperbaric oxygen therapy as an intensive care treatment, some of whom have pre-existing airway obstruction. Spirometers are the ideal instruments for measuring airway obstruction, but peak flow meters are useful and versatile devices. The behaviour of both types of device was therefore studied in a hyperbaric unit under conditions of increased pressure. It is important to have a non-electrical indicator of airway obstruction, to minimize the fire risk in the hyperoxic environment. The hypothesis was tested that, assuming that dynamic resistance is unchanged, both the Wright's standard and mini-peak flow meters would over-read peak expiratory flow (PEF) under increased pressure when compared with a volumetric spirometer, as the latter is unaffected by air density. It was postulated that a correction factor could be derived so that PEF meters could be used in this setting. Seven normal subjects performed volume-dependent spirometry to derive PEF, and manoeuvres using both standard and mini PEF meters at sea level, under hyperbaric conditions at 303, 253 and 152 kPa (3, 2.5 and 1.5 atmospheres respectively; 1 atmosphere absolute=101.08 kPa), and again at sea level. There was a progressive and significant decline in PEF with increasing pressure as measured by the spirometer (69.46+/-0.8% baseline at 303 kPa compared with 101 kPa), while the PEF meters showed a progressive increase in their readings (an increase of 7.86+/-1.69% at 303 kPa with the mini PEF meter). Using these data points, a correction factor was derived which allows appropriate values to be calculated from the Wright's meter readings under these conditions.     

即时高压氧治疗对大鼠脑缺血后脑水肿及水通道蛋白4 表达的影响

目的观察即时高压氧治疗对缺血早期脑水肿形成的影响,并探讨其可能的机制。方法健康成年雄性清洁级Sprague-Dawley 大鼠18 只,随机分为假手术组(n=6)、对照组(n=6)和高压氧组(n=6)。对照组及高压氧组采用线栓法制备大鼠大脑中动脉阻塞(MCAO)模型,其中高压氧组在舱内升压时进行模型制备并予高压氧治疗60 min。各组均于术后6 h 行Longa 评分法评分,采用干湿比重法检测脑组织含水量,免疫组化SP 法观察水通道蛋白4 (AQP4)表达,应用图像分析系统进行半定量分析。结果与对照组比较,高压氧组大鼠神经功能评分改善(P<0.05),缺血半球脑含水量减少(P<0.05),AQP4 表达量减少(P<0.05)。结论即时高压氧治疗可有效缓解脑缺血后症状,对脑水肿的发生有抑制作用;AQP4 表达减少可能是其机制之一。     

高压氧对脑缺血再灌注海马神经元Bcl-2和Bax蛋白表达的影响

目的观察高压氧(HBO)作用下脑缺血再灌注海马CA1区神经元Bcl-2和Bax蛋白表达的变化情况,进一步研讨高压氧治疗脑缺血再灌注损伤、减轻神经元凋亡从而发挥保护作用的机制。方法沙土鼠20只,采用随机数字法将实验动物分为正常对照组、缺血组、0.15MPaHBO治疗组、0.25MPaHBO治疗组,0.25MPa压力空气(hyperbaricair,HBA)对照组,每组4只动物。采用“双侧颈总动脉阻断法”前脑缺血模型,缺血20min后再灌注3d,并用0.15MPa和0.25MPa压力的高压氧治疗(60min/d,连续3d)后,应用免疫组化LSAB方法,观察高压氧对海马CA1区神经元凋亡相关基因Bcl-2和Bax的蛋白表达的影响。结果沙土鼠脑缺血再灌注3d组海马CA1区大量神经元表达Bax蛋白,并且神经元发生凋亡,未见神经元表达Bcl-2蛋白;高压氧治疗组则大量神经元表达Bcl-2蛋白,并且0.25MPa高压氧治疗组比0.15MPa高压氧治疗组变化更显著,而各组表达Bax蛋白的神经元数目无明显变化,但高压氧治疗组Bax蛋白阳性的神经元形态正常。结论HBO暴露可诱导大量神经元表达Bcl-2蛋白,对Bax蛋白表达则无明显作用,使Bcl-2和Bax蛋白表达的比值增高,从而起到保护神经元的作用,这可视为HBO治疗脑缺血性损伤减少神经元凋亡的机制之一。     

Hyperbaric oxygen attenuates lipopolysaccharide-induced acute lung injury

OBJECTIVES: To study the effect of hyperbaric oxygen therapy in alleviating acute lung injury induced by lipopolysaccharide (LPS) in rats.DESIGN AND INTERVENTIONS: The rats received an intraperitoneal injection of LPS (15 mg/kg). Animals were either breathing air at 1 ATA or subjected to hyperbaric oxygen (HBO(2)) therapy. The HBO(2) therapy was carried out in a hyperbaric chamber at a pressure of 3 ATA for 90 min. In another two groups, LPS-treated rats also received intraperitoneal injection of N(omega)-nitro-L-arginine (LNAME, 25 mg/kg) or L-N(6)-(iminoethyl)lysine (LNIL, 10 ml/kg). Another two groups of LPS-treated rats were subjected to HBO(2) exposure after the injection of L-NAME or L-NIL.MEASUREMENTS AND MAIN RESULTS: The bronchoalveolar lavage (BAL) was done into the left lung at 7.5 h after intraperitoneal injection of LPS. Parts of the right lung were excised for myeloperoxidase measurement, whereas the rest was collected for wet/dry ratio determination. LPS significantly increased the nitrite/nitrate (NO(x)(-)) concentration (34.4+/-15.7 vs 4.5+/-3.1 microM), LDH activity (66+/-17 vs 46+/-15 mAbs/min), and protein concentration (373+/-119 vs 180+/-90 mg/l) in the BAL fluid. Treatment with HBO(2) immediately after the injection of LPS enhanced the increase of NO(x)(-) production, but reduced the LDH and protein in BAL fluid to the control levels. Pretreatment with either L-NAME or L-NIL abolished the increase of NO(x)(-) in the BAL fluid and further elevated the LDH level and protein concentration.CONCLUSION: Our results suggested that HBO(2) alleviates the LPS-induced acute lung injury, which may be related to the enhancement of nitric oxide production.     

高压氧干预后局灶性脑缺血再灌注损伤模型大鼠c-fos的表达

背景：高压氧可增加氧弥散能力,从而改善脑水肿和脑组织缺氧,促进病灶区脑细胞的生理功能恢复、侧支循环的建立和脑细胞再生修复。 目的：观察高压氧对大鼠急性局灶性脑缺血再灌注损伤后不同时间点c-fos癌基因表达的影响。 设计：随机分组动物实验。单位：解放军第四军医大学唐都医院急诊科、西安高新医院检验中心、解放军空军总医院、解放军第四军医大学航空航天医学系高压氧治疗中心。 材料：实验于2002-04在解放军第四军医大学航空航天医学系高压氧治疗中心完成,选用65只生后2个月健康雄性SD大鼠。 方法：随机摸球法将大鼠分为4组,模型组（n=20）：参照Koizumi等设计的方法,制备大鼠大脑中动脉缺血模型;正常对照组（n=5）：手术方式同模型组,但不阻断动脉血流;纯氧治疗组（n=20）：手术过程同模型组,动物缺血1h后抽出栓子,分别在插入栓子后2,9,21,45,69h将动物置于高压舱内,常压下吸100%纯氧。高压氧治疗组（n=20）：手术过程同模型组,动物缺血1h后抽出栓子,分别在插入栓子后2,9,21,45,69h将动物置于高压氧舱内,0.25MPa吸纯氧1h。主要观察指标：利用免疫组织化学和病理组织学法观察各组大鼠脑缺血再灌注5,12,24,72h脑皮质、视前区与纹状体中性白细胞浸润及c-fos癌基因蛋白及阳性细胞表达的变化;计算脑缺血再灌注72h皮质、纹状体内侧区与视前区神经元坏死程度、大鼠左侧半球脑血管渗漏面积。 结果：纳入大鼠65只均进入结果分析。①视前区c-fos阳性产物主要集中于中部。对侧皮质少见c-fos阳性反应,视前区有轻度表达,纹状体呈中等强度的反应。缺血12h,c-fos阳性产物在上述区域开始减弱,24h强度明显减弱!高压氧治疗组皮质和视前区较单纯缺血组c-fos阳性产物强度明显减弱!缺血再灌注12h,高压氧治疗组视前区、纹状体中性白细胞数明显低于模型组（P〈0.05）;缺血再灌注24h,脑皮质、视前区、纹状体中性白细胞低于模型组（P〈0.05）。②高压氧治疗组血管渗漏面积与单纯模型组相比明显缩小（P〈0.05）;缺血再灌注72h,高压氧治疗组视交叉平面皮质、纹状体内侧区与视前区神经细胞损伤数目较模型组明显减轻（P〈0.05）,假手术组未见神经元损伤。 结论：高压氧可明显缩小大鼠急性局灶性脑缺血再灌注损伤的血管渗漏面积,减轻神经系统症状,抑制中性白细胞浸润,抑制梗塞区c-fos癌基因表达,减少“半影区”神经元坏死。