Oxygen-free radicals and lipid peroxidation in adult respiratory distress syndrome

Activated species of oxygen have been implicated as mediators of some acute lung injury. In adult respiratory distress syndrome (ARDS), polymorphonuclear leukocytes accumulate in the lung and release excessive amounts of O₂-derived products into the extracellular environment. The effects of these O₂ products on lung tissue are multiple. In particular, they can initiate lipid peroxydation in cellular membranes. Excessive lipid peroxydation in membranes destroys cells such as vascular endothelium. Lipid peroxides are also detrimental to cellular functions. Lipid peroxydation could then play a role in the pathogenesis of ARDS.     

Acute respiratory failure following pharmacologically induced hyperventilation: an experimental animal study

The pulmonary effects of hyperventilation following infusion of sodium salicylate into the cisterna magna was studied in 16 spontaneously breathing adult sheep. We found a fall in PaO₂, a decrease in the static compliance of the respiratory system, abnormal chest roentgenographic films, and grossly abnormal lungs following 3.5 to 13 h of hyperventilation. A control group of 15 sheep (10 sheep similarly injected with sodium salicylate, but then sedated and paralyzed and ventilated at normal tidal volume and respiratory rate on a mechanical ventilator, and 5 sheep infused with saline alone and breathing spontaneously) showed no pulmonary or arterial blood gas abnormalities. We conclude that prolonged hyperventilation under the conditions of this experiment precipitated events that resulted in acute lung injury.     

补体缺陷及其疾病

补体系统作为机体重要的免疫效应及其链式放大系统,是连接固有免疫和适应性免疫的重要桥梁,同时作为机体免疫调控网络的重要环节,在维持机体免疫自稳方面发挥重要作用。有文献已报道补体系统中有多种成分缺陷及补体的数量和质量存在异常的个体通常对某些疾病的易感性增加或直接导致相关疾病的发生,该文对目前常见的补体缺陷及其参与相关疾病发病机制的研究进展作一综述,期望为疾病的实验诊断提供新的思路。     

Oxygen tolerance in patients with acute respiratory failure

Objective: To search for a threshold of pulmonary oxygen toxicity in patients with acute respiratory failure. Design: Retrospective study over a 10-year period. Setting: Three intensive care units of two university hospitals. Patients and participants: Seventy-four patients with acute respiratory failure ventilated continuously with a FIO₂ L 0.9 for at least 48 h were selected. Interventions: Information regarding status, scoring, diagnosis and therapeutic interventions upon admission and ICU course were extracted from the patients' charts. Measurements and results: We found that total exposure [mean (standard error of the mean) ] to a FIO₂ of 0.9 (TE 90) or more was 5.6 (1.1) days in the 17 survivors (S) versus 5.9 (0.5) days in the 57 non-survivors (D) (NS). Total exposure time to a FIO₂ more than 0.5 (TE 50) was 16.5 (2.6) days in S and 11.2 (1) days in D (p < 0.05). The PaO₂/FIO₂ ratio became significantly higher in S only 5 days after beginning FIO₂ of 0.9 or more. Hypoxemia was not frequent at the time of death, whereas in 70 % of the non-survivors there were at least three organ failures in the last 48 h. In univariate analysis, the duration of exposure to FIO₂ of 0.9 or more was not different in survivors and non-survivors, and the average total duration of exposure to FIO₂ of more than 0.5 was even longer in survivors. In multivariate analysis, exposure shorter than 10 days to FIO₂ more than 0.5 and exposure longer than 4 days to a FIO₂ of 0.9 or more were significantly associated with death. However, despite a larger exposure to a FIO₂ of 0.9 or more during the last 5 years of the study, the trend moved towards a higher survival rate during this period compared with the first 5 years of the study. Conclusions: Thus, our data provide circumstantial evidence that the lungs of patients with acute respiratory failure might exhibit some relative resistance to prolonged oxygen exposure. Therefore, it might be worthwhile carrying out a prospective study of different FIO₂ strategies in such patients. Received: 14 February 1997 Accepted: 2 March 1998     

Complement,granulocytes, and shock lung

Intravascular leukostasis in the pulmonary microvasculature is a cardinal early histologic finding in patients with shock lung. Identical leukostasis is also observed in patients undergoing extracorporeal hemodialysis with cellophane membrane dialyzers, and it has been documented that the accumulation of granulocyte plugs in the lung is mediated by complement activation triggered by dialyzer cellophane. The C5a-desarg so generated causes peripheral blood granulocytes to aggregate, and the aggregates so formed embolize to the lung, where they cause occlusion of the microvasculature and increased capillary leakage, manifested by interstitial and alveolar edema. In vitro studies suggest that this endothelial damage is mediated by hydrogen peroxide from the adherent granulocytes. Most importantly, a close correlation has been found between the presence of C5a-desarg in plasma and the subsequent onset of shock lung in patients after trauma, burns, and sepsis. As exemplified by hemodialysis leukopenia, C5a-desarg-mediated pulmonary leukostasis is a self-limiting process because of selective down-regulation of granulocyte receptors for C5a-desarg—a mechanism that primarily limits the lung damage associated with intravascular complement activation.     

左旋精氨酸对兔肺缺血/再灌注损伤时细胞凋亡的影响

目的观察左旋精氨酸对免肺缺血／再灌注损伤中细胞凋亡的影响。方法复制单侧免肺缺血／再灌注损伤模型．随机分为三组：对照组（C组）、缺血／再灌注组（I／R组）和左旋精氨酸组（L—Arg组），每组10只。再灌注180min时取肺组织，观察超氧化物歧化酶（SOD）活性、丙二醛（MDA）浓度、一氧化氮（NO）含量、肺湿干比（W／D）、肺泡损伤数定量评价指标（IQA）及肺组织细胞凋亡指数（At）。结果I／R组与C组比较，SOD活性、NO含量明显降低（P〈0．01），MDA、W／D、IQA、AI明显升高（P〈0．01），L—Arg组与I／R组相比较，SOD活性、NO含量均明显升高（P〈0．01），MDA、W／D、IQA、AI不同程度降低（P〈0．05）。结论左旋精氨酸可通过提高体内NO水平、降低氧自由基水平、减轻脂质过氧化反应，抑制肺组织细胞凋亡，从而减轻肺损伤。     

颈髓损伤患者血液流变学及抗氧化能力的临床观察

目的：观察颈髓损伤患者血液流变学及机体抗氧化能力的变化并探讨其临床意义。方法：40例颈髓损伤患者治疗前后根据脊髓损伤的神经和功能分类标准，评定脊髓损伤的程度及疗效。治疗前后检测血液流变学及超氧化物歧化酶（SOD）和丙二醛（MDA）水平，与对照组比较，观察颈髓损伤患者血液流变学及抗氧化能力的变化。结果：颈髓损伤患者治疗前血液粘皮增高，表现为全血粘度高低切变值、血浆粘皮及血沉均高于对照组。血清SOD活力降低且MDA含量增高，提示机体抗氧化能力下降。治疗后运动及感觉功能评分均有明显改善，血液粘度下降且抗氧化能力提高。结论：颈髓损伤可出现血液粘皮增尚及抗氧化能力下降，在治疗中应予重视。     

阿拓莫兰对缺血再灌注损伤肝脏的保护作用

目的：探讨阿拓莫兰对家兔肝缺血再灌注（I／R）损伤肝脏的保护作用。方法：将20只健康新西兰大耳白兔随机分为对照,阿拓莫兰保护组，制备家兔肝I／R损伤模型，观察阿拓莫兰对谷丙转氨酶（ALT），谷草转氨酶（AST）和肝组织黄嘌呤氧化酶（XO），超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GSH－PX）活性，丙二醛（MDA）含量及肝细胞形态学变化的影响。结果：肝I／R损伤期间，ALT，AST，XO活性及MDA含量均明显或高（P＜0．05），SOD和GSH－PX活性显著下降（P＜0．05），肝细胞形态学发生异常变化，使用阿拓莫兰后，上述指标的异常变化显著减轻，其差异有显著意义（P＜0．05），结论：阿拓莫兰通过清除氧自由基（OFR），对I／R损伤肝脏有积极的防治作用。     

血清补体对肝癌诊断、治疗及预后的价值

采用单向免疫扩散法，对肝癌及肝硬化患者行７种血清补体检测。原发性肝癌患者血清补体含量明显增高（Ｐ＜０．０１），以ＡＦＰ阴性的肝癌升高最为明显，且与ＡＦＰ无相关性，肝癌切除后补体值降低，复发时再次升高。肝硬化患者的血清补体含量明显低于对照组。揭示血清补体成份的测定，对肝癌的诊断、鉴别诊断、预后和转归有重要意义。     

Acute hypoxemic respiratory failure in children: case mix and the utility of respiratory severity indices

Objective: Acute hypoxemic respiratory failure (AHRF) is a common reason for emergency pediatric intensive care. An objective assessment of disease severity from acute physiological parameters would be of value in clinical practice and in the design of clinical trials. We hypothesised that there was a difference in the best early respiratory indices in those who died compared with those who survived. Design: A prospective observational study of 118 consecutive AHRF admissions with data analysis incorporating all blood gases. Setting: A pediatric intensive care unit in a national children's hospital. Interventions: None. Results: Mortality was 26/118, 22 % (95 % confidence interval 18–26 %). There were no significant differences in the best alveolar-arterial oxygen tension gradient (A-aDO₂, torr), oxygenation index (OI), ventilation index (VI), or PaO₂/FIO₂ during the first 2 days of intensive care between the survivors and non-survivors. Only the mean airway pressure (MAP, cm H₂O) used for supportive care was significantly different on days 0 and 1 (p K 0.05) with higher pressure being used in non-survivors. Multiple logistic regression analysis did not identify any gas exchange or ventilator parameter independently associated with mortality. Rather, all deaths were associated with coincident pathology or multi-organ system failure, or perceived treatment futility due to pre-existing diagnoses instead of unsupportable respiratory failure. When using previously published predictors of outcome (VI > 40 and OI > 40; A-aDO₂ > 450 for 24 h; A-aDO₂ > 470 or MAP > 23; or A-aDO₂ > 420) the risk of mortality was overestimated significantly in the current population. Conclusion: The original hypothesis was refuted. It appears that the outcome of AHRF in present day pediatric critical care is principally related to the severity of associated pathology and now no longer solely to the severity of respiratory failure. Further studies in larger series are needed to confirm these findings. Received: 16 December 1997 Accepted: 31 March 1998     

丹参对大鼠肝脏缺血再灌注损伤的抗氧化作用

目的探讨丹参对大鼠缺血再灌注损伤肝脏的抗氧化作用。方法建立大鼠全肝缺血再灌注模型,60只大鼠随机分为三组,每组20只,分别为对照组(A组)、肝缺血/再灌注组(B组)和肝缺血/再灌注加丹参治疗组(C组),分别在肝缺血前、缺血45min、再灌注45min共3个时相点,检测血浆超氧化物歧化酶(SOD)活性、黄嘌呤氧化酶(XO)活性、丙二醛(MDA)浓度以及血清谷丙转氨酶(ALT)活性。结果肝缺血/再灌注组,血浆XO、MDA及ALT显著高于对照组、SOD明显低于对照组(P<0.05和<0.01)。而丹参治疗组与缺血/再灌注组比较,上述指标均有显著性差异(P<0.05和<0.01)。结论丹参可通过降低氧自由基水平(增强SOD活性、减弱XO活性),拮抗脂质过氧化反应(降低MDA浓度),从而减轻肝脏缺血再灌注损伤。     

氧自由基在急性期多器官功能障碍综合征心肌损伤中的变化

目的观察急性期多器官功能障碍综合征(MODS)大鼠心肌的病理变化及心肌组织与血浆中氧自由基的改变,探讨其意义。方法大鼠腹腔注射酵母多糖液体石蜡混悬液制备MODS动物模型作为实验组,对照组注射等体积无菌生理盐水,检测血浆LPO、SOD、心肌酶和心肌组织MDA和SOD在不同时间点的动态变化,并做心肌HE染色,观察病理变化。结果实验组与对照组比较,血浆和心肌中LPO、MDA、CKMB、LDH、GOT在6h时间点即有明显升高(P<0.05),12h时仍有升高趋势(P<0.01),24h时升高最明显(P<0.01),而SOD呈明显下降趋势。心肌病理学改变呈间质充血、水肿,大量炎性细胞浸润。结论氧自由基可能参与了急性期MODS大鼠心肌损伤的发生。     

氧浓度对体外循环后肺损伤影响的实验研究

目的：观察体外循环(CPB)前后吸入不同浓度氧气对肺脏缺血／再灌注损伤的影响。方法：建立大鼠体外循环模型，体外循环时间为120min。根据机械通气期间吸入氧浓度的不同分100％氧通气组(n=8)和50％氧通气组(n=8)。实验过程记录血压和心率的变化，并进行血气分析。CPB后60min实验结束时取肺组织。测定并计算丙二醛(MDA)、髓过氧化物酶(MPO)和组织含水量。结果：体外循环前后血压和心率相对稳定。体外循环过程中红细胞压积(HCT)和转流量两组没有明显差异。100％氧通气组的PaO2在CPB结束后5min和CPB后60min均低于CPB前，而50％氧通气组没有明显变化，而且CPB后肺组织中MDA和MP0较低．肺组织含水量也低于100％氧通气组。结论：体外循环前后吸入高浓度氧可加重氧化性肺损伤，应使用接近生理水平的较低浓度的氧气以减轻肺损伤。     

Safety and efficacy of a sustained inflation for alveolar recruitment in adults with respiratory failure

Objective: To assess the safety and efficacy of a sustained inflation, used as a lung volume recruitment maneuver in ventilated patients with hypoxemic respiratory failure.¶Design: Prospective data collection as part of a quality assurance program following introduction of a lung volume recruitment guideline in the intensive care unit.¶Setting: Academic medical-surgical critical care unit.¶Patients: Hypoxemic patients with bilateral pulmonary infiltrates. Patients with chronic obstructive pulmonary disease, pulmonary barotrauma and hemodynamic instability were excluded.¶Interventions: A sustained inflation using a pressure of 30 to 45 cmH₂O was applied for 20 s. The pressure was determined as the lesser of 45 cmH₂O or the peak pressure while ventilated at a tidal volume of 12 ml/kg. Intra-arterial blood pressure and pulse oximetry were monitored continuously.¶Measurements and results: Significant improvement in oxygenation occurred in the majority of patients within 10 min. The mean oxygen saturation improved from 86.9 ± 5.5 to 94.3 ± 2.3 % (p < 0.01). No significant adverse effects were noted: hypotension and mild oxygen desaturation occurred in some patients during the 20-s inflation, reversing rapidly after inflation was terminated. No barotrauma occurred.¶Conclusions: A sustained inflation is a safe, clinically applicable method of lung volume recruitment which improves oxygenation in selected patients and may have a role in ventilatory management.     

肝癌患者血清补体检测的临床意义

目的研究肝癌患者血清补体水平及其变化的临床意义。方法透射免疫比浊法检测C3、C4,酶法检测CH50在42例肝癌与12例肝硬化患者、38例正常人血清中含量并进行对比,分析肝癌及其不同临床分期和手术前后C3、C4和CH50的变化。结果肝癌患者血清C3水平与正常人无明显差别(P>0.05),C4显著降低(P<0.01),CH50显著增高(P<0.01),以甲胎球蛋白(AFP)阴性的肝癌最为明显,且与AFP无相关性;肝癌不同临床分期补体水平有不同表现;手术后C4明显升高(P<0.05),CH50明显下降(P<0.05),复发时再次升高;肝硬化患者的血清补体含量明显低于正常人(P<0.05)。结论肝癌患者血清补体水平存在明显异常,检测血清C3、C4和CH50对肝癌诊断、鉴别诊断、治疗中的动态观察及预后均有重要意义。     

PEEP对急性呼吸衰竭病人全身氧供给的影响

目的探讨呼气末正压（ＰＥＥＰ）通气对急性呼吸衰竭病人全身氧供给（ＤＯ２）的影响。方法选择２０例急性呼吸衰竭机械通气病人,放置Ｓｗａｎ－Ｇａｎｚ导管,依次调节ＰＥＥＰ为０、０４９ｋＰａ、０９８ｋＰａ、１４７ｋＰａ四种压力水平,分别测定气体交换功能及氧动力学指标。结果ＰＥＥＰ为０４８ｋＰａ时动脉血氧分压（ＰａＯ２）即开始明显升高（Ｐ＜０５）,心脏指数（ＣＩ）却出现降低（Ｐ＜００５）,随着ＰＥＥＰ增加,ＣＩ逐渐下降。ＤＯ２在ＰＥＥＰ为０９８ｋＰａ以下时变化不显著,在１４７ｋＰａ时出现显著下降（Ｐ＜００５）,而氧摄取率（ＥｘｔＯ２）则有所增加（Ｐ＜００５）。结论ＰＥＥＰ使用不能明显提高ＤＯ２,高水平的ＰＥＥＰ可以降低ＤＯ２,必须采取措施提高ＣＩ才能使ＤＯ２增加。     

Effect of inspired oxygen fraction on alveolar derecruitment in acute respiratory distress syndrome

Objective High fractions of inspired oxygen (FIO₂) used in acute lung injury (ALI) may promote resorption atelectasis. The impact of derecruitment related to high FIO₂ in ALI is debated. We evaluated derecruitment with 100% vs. 60% FIO₂ at two levels of positive end-expiratory pressure (PEEP).Patients Fourteen consecutive patients with ALI were studied.Interventions Recruited volume at two PEEP levels was computed from two pressure-volume curves, recorded from PEEP and from zero end-expiratory pressure, using the sinusoidal flow modulation method. PEEP-induced recruitment was measured during prolonged expiration as the difference between the two curves at a given pressure. PaO₂/FIO₂ was also measured. PEEP was 5 ± 1 or 14 ± 3 cmH₂O and FIO₂ was 60% or 100%, yielding four combinations. We looked for differences between the beginning and end of a 30-min period with each combination.Measurement and results With low PEEP and 100% FIO₂, recruited volume decreased significantly from 68 ± 53 to 39 ± 43 ml and PaO₂/FIO₂ from 196 ± 104 to 153 ± 83 mmHg. With the three other combinations (low PEEP and 60% FIO₂ or high PEEP and 60% or 100% FIO₂) none of the parameters decreased significantly.Conclusion In mechanically ventilated patients with ALI the breathing of pure oxygen leads to derecruitment, which is prevented by high PEEP.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.This article is discussed in the editorial available at: