Involvement of Mitochondrial and Reactive Oxygen Species in the Sonodynamic Toxicity of Chlorin e6 in Human Leukemia K562 Cells

It is well accepted that sonodynamic therapy (SDT) exerts cytotoxicity and anti-tumor activity in many human tumors through the induction of cell apoptosis. The aim of the work described here was to study the effect of chlorin e6 (Ce6)-mediated SDT on human chronic myelogenous leukemia K562 cells. Our results indicate that Ce6-mediated SDT can suppress the viability of K562 cells. SDT caused apoptosis as analyzed by annexin V-phycoerythrin/7-amino-actinomycin D staining as well as cleavage of caspase 3 and the polypeptide poly(ADP-ribose) polymerase. After SDT exposure, loss of mitochondrial membrane potential, translocation of Bax from cytoplasm to mitochondria and activation of caspase 9 indicated that the mitochondrial-related apoptotic pathway might be activated. This process was accompanied by rapid generation of reactive oxygen species (ROS). Scavenging of ROS significantly blocked caspase-3 expression and the killing effect of SDT on K562 cells. Stress-activated protein kinases c-jun NH2-terminal kinase (JNK) and the p38 mitogen-activated protein kinase were activated after SDT treatment. Together, these findings indicate that Ce6-mediated SDT triggers mitochondria- and caspase-dependent apoptosis; oxidative injury may play a vital role in apoptotic signaling cascades.     

Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia

Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble in water. Many new nanoplatforms have been successfully established to improve the delivery efficiency of PS drugs. However, few reported studies have investigated how the carrier microenvironment may affect the photophysical properties of photosensitizer (PS) drugs and subsequently, their biological efficacy in killing malignant cells. In this study, we describe the modulation of type I and II photoactivation processes of the photosensitizer, 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment. Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles increased photoactivations from type II to type I mechanisms, which significantly increased the generation of O₂⁻ through the electron transfer pathway over ¹O₂ production through energy transfer process. The PDPA micelles led to enhanced phototoxicity over the electron-deficient poly(d,l-lactide) control in multiple cancer cell lines under argon-saturated conditions. These data suggest that micelle carriers may not only improve the bioavailability of photosensitizer drugs, but also modulate photophysical properties for improved PDT efficacy.     

Generation of Reactive Oxygen Species in Heterogeneously Sonoporated Cells by Microbubbles with Single-Pulse Ultrasound

To develop and realize sonoporation-based macromolecule delivery, it is important to understand the underlying cellular bioeffects involved. It is known that an appropriate level of reactive oxygen species (ROS) is necessary to maintain normal physiologic function, but excessive ROS triggers adverse downstream bioeffects. However, it is still unclear whether a relationship exists between intracellular ROS levels and sonoporation. Using a customized platform for 1.5-MHz ultrasound exposure (13.33 µs duration and 0.70?MPa peak negative pressure) and imaging the dynamics of sonoporation and intracellular ROS at the single-cell level, we quantified the exogenous molecular uptake and the concentration of intracellular ROS indicator to evaluate the extent of sonoporation and ROS change, respectively. Our results revealed that the intracellular ROS level was correlated with the degree of the sonoporation. (i) Within ~120?s of the onset of ultrasound, during which membrane perforation and complete membrane resealing occurred, intracellular ROS rapidly decreased because of extracellular diffusion of dichlorofluorescein through the perforated membrane and positively correlated with the degree of the sonoporation. (ii) In the following 270?s (120–390?s post-exposure), ROS generation in reversibly sonoporated cells gradually increased and was positively correlated with the degree of the sonoporation. (iii) The ROS level in irreversibly sonoporated cells reduced to depletion during this time interval. It is possible that ROS generation in reversibly sonoporated cells can impact their long-term fate. These results thus provide new insight into the biological response to sonoporation.     

Efficacy of Indocyanine Green-Mediated Sonodynamic Therapy on Rheumatoid Arthritis Fibroblast-like Synoviocytes

Sonodynamic therapy (SDT) has become a new therapeutic method because of its activation of certain sensitizers by ultrasound. Some studies have reported that indocyanine green (ICG) has the characteristics of a sonosensitizer and favorable fluorescence imaging in synovitis of early inflammatory arthritis. In this study, we aimed to investigate the cytotoxic effect of ICG-mediated SDT on MH7A cells in vitro and the potential mechanisms involved. ICG was found to be taken up mainly in cytoplasm, with maximal uptake in 4 h. Cell viability in ICG-mediated SDT (SDT-0.5 and SDT-1.0) groups decreased significantly to 73.09 ± 1.97% and 54.24 ± 4.66%, respectively; cell apoptosis increased significantly to 26.43 ± 0.91% and 45.93 ± 6.17%, respectively. Moreover, marked loss in mitochondrial membrane potential and greatly increased generation of reactive oxygen species were observed in ICG-mediated SDT groups. Interestingly, the loss in cell viability could be effectively rescued with pretreatment with the reactive oxygen species scavenger N-acetylcysteine. These results indicate that ICG-mediated SDT is cytotoxic to fibroblast-like synoviocytes and is a potential modality for targeted therapy of synovitis in rheumatoid arthritis.     

光动力学疗法对小鼠移植瘤细胞增殖微血管及血流量的影响

为进一步探讨光动力学疗法（ＰＤＴ）的体内作用机理，对小鼠前胃癌移植瘤ＰＤＴ治疗后的瘤组织形态学、增殖动力学及微循环的变化进行了观察．结果表明，ＰＤＴ在短期内即产生对瘤细胞增殖的抑制作用，表现为肿瘤细胞标记指数（ＬＩ）及瘤核ＤＮＡ含量逐渐减少．血管内皮细胞是ＰＤＴ效应的最初靶部位，而后出现继发性微血管充血扩张、红细胞聚集、血栓形成、出血和微血管完全破坏一系列渐进性改变。因此提高光敏剂的细胞毒作用和加重肿瘤组织微循环的损害是提高ＰＤＴ体内疗效的重要途径．     

喜泊芬对人食管癌Eca-109细胞的光动力效应

目的：探讨不同孵育浓度和不同光照剂量密度喜泊芬介导的光动力治疗（photodynamic therapy,PDT）对人食管癌细胞Eca-109体外效应的影响。方法：以不同浓度喜泊芬孵育食管癌Eca-109细胞,并分别在不同光照剂量密度（0、12、24、30J/cm2）下行PDT,24h后通过四甲基偶氮唑盐（MTT）法检测细胞生存率。结果：不同孵育浓度喜泊芬在4种不同光照剂量密度下食管癌Eca-109细胞生存率间均有显著差异（P〈0.01）。在同一光照剂量密度下,不同喜泊芬浓度的食管癌Eca-109细胞的生存率有显著差异（P〈0.01）,而同一喜泊芬孵育浓度下,不同光照剂量密度的食管癌Eca-109细胞的生存率有显著差异（P〈0.01）。结论：喜泊芬的不同孵育浓度和不同光照剂量密度对人食管癌Eca-109细胞体外PDT效应有显著影响。     

声动力疗法的机制研究进展

声动力疗法是一种组织穿透性良好、精度高、副作用小的无创治疗手段。超声驱动的声动力治疗具有无创性、靶向性和组织穿透性等优势,且可显著增强肿瘤治疗效果,在肿瘤防治方面具有良好的应用前景。目前声动力疗法机制研究中尚缺乏超声机械力效应概述,本文就空化效应和机械力效应产生活性氧诱导钙超载途径进行综述。     

吡罗昔康声动力效应对乳腺癌细胞生物学作用及其机制的实验研究

目的 探讨吡罗昔康介导的声动力效应对乳腺癌细胞的急性细胞毒作用及其作用机制。方法 采用噻唑蓝（MTT）比色法检测吡罗昔康声动力效应对乳腺癌细胞的急性杀伤作用和活性氧清除剂对声动力作用的影响，用透射电镜观察细胞超微结构，用吖啶橙／溴化乙啶（AO／EB）双染法和流式细胞仪（FCM）检测细胞凋亡、线粒体跨膜电位（MMP）及活性氧（ROS）水平。结果 单纯应用超声有杀伤细胞和诱导细胞凋亡的作用，而吡罗昔康存在时，这一作用更为显著，声动力组细胞凋亡率和ROS水平亦明显高于单纯超声组，而MMP却显著低于后者。且组氨酸能够显著抑制吡罗昔康声动力效应，而甘露醇对其无明显影响。结论吡罗昔康介导的声动力作用对乳腺癌细胞具有显著的杀伤效应和诱导凋亡作用，这可能与声动力作用后MDA—M昏231细胞内ROS增加所致MMP下降有关。     

Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization

Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising non-viral delivery systems for pulmonary inhalation gene therapy and thus require sufficient stability during nebulization. The structure and stability of four different PEI–DNA polyplexes, namely branched (bPEI), linear (linPEI), poly(ethylene glycol)-grafted PEI (PEGPEI), biodegradable (bioPEI) PEI with DNA, were investigated. Using atomic force microscopy, the morphology of DNA and polyplexes before and after both air-jet and ultrasonic nebulization was characterized. The influence of nebulization on physico-chemical properties, particle size and zeta potential, was studied. Efficient DNA condensation to spherical particles was achieved with bPEI (90 nm) and PEGPEI (110 nm). By contrast, incomplete DNA condensations, seen as flower structures, were observed with linPEI (110 nm) and bioPEI (105 nm). Air-jet nebulization altered the polyplex structure to a greater extent than ultrasonic nebulization and resulted mainly in smaller and non-spherical particles (30–200 nm). Ultrasonic nebulization did not change the spherical structure or particle size of the polyplexes. In particular, the shape and size of the PEGPEI polyplexes did not change. We conclude that ultrasonic nebulization is a milder aerosolization method for gene delivery systems based on PEI. Additionally, PEGPEI–DNA polyplexes seem to be more stable than their counterparts, which may be advantageous in pulmonary inhalation gene therapy.     

超声引导下微波介入治疗大肝癌的实验研究及临床应用

目的进一步探讨超声引导下微波治疗大肝癌的可行性和疗效。方法采用分次多点多部位由深到浅低功率长时间分段微波凝固,对10个65斤重的猪肝和2只狗进行了实验研究;60例大肝癌患者进行了超声引导下微波治疗。结果微波治疗后两个或多个坏死区叠加,凝固坏死区加大。离体猪肝坏死区达到6cm×6cm,狗肝坏死区为5cm×6cm。所有病例治疗后肿块缩小,肿瘤内血流消失或减少;22例CT检查,肿块缩小,18例无强化;28例超声引导下活检大片坏死。治疗后全身情况好转,AFP和肝功能改善,生活质量提高。无严重并发症发生。随访3～28个月,51例存活。结论实验研究表明改进微波治疗方法,坏死区加大,超声引导微波治疗大肝癌也有较好的疗效。     

光动力疗法治疗皮肤鲍温病的系统评价

目的系统评价光动力疗法（photodynamic therapy,PDT）治疗皮肤鲍温病的疗效与安全性。方法计算机检索PubMed、OVID、Cochrane图书馆临床对照试验库、CBM和CNKI等电子数据库,纳入PDT治疗皮肤鲍温病的随机对照试验（RCT）。检索时间从1966年1月至2010年3月。检索语种限中、英文。对纳入RCT进行质量评价,提取有效数据,采用RevMan 5.0.23版软件进行Meta分析。结果共纳入5个RCT,共354例患者,496处皮损,其中试验组皮损237处,对照组皮损259处。Meta分析结果显示：PDT组的治愈率高于安慰剂组[RR=4.16,95%CI（1.69,10.25）]或外用氟尿嘧啶软膏治疗组[RR=1.38,95%CI（1.12,1.71）],而与冷冻治疗组无显著差别;PDT组的美容效果评价优于冷冻组[RR=1.48,95%CI（1.18,1.87）]或外用氟尿嘧啶软膏治疗组[RR=1.51,95%CI（1.05,2.15）];PDT组的复发率低于安慰剂治疗组[RR=0.29,95%CI（0.10,0.86）],但与冷冻组或外用氟尿嘧啶软膏组无显著差异。以红光为光源的PDT组治愈率高于绿光光源组的PDT[RR=1.29,95%CI（1.02,1.65）],复发率低于后者[RR=0.20,95%CI（0.05,0.87）]。两次光照治疗方案与单次光照治疗方案的治愈率及美容效果评价无显著差异。PDT治疗的不良反应包括不同程度的疼痛、局部感觉异常、局部炎症反应、色素沉着、结痂。结论现有有限证据表明,PDT治疗皮肤鲍温病的疗效优于安慰剂、冷冻或外用氟尿嘧啶软膏等对照治疗,复发率低于安慰剂,不良反应与对照组相似;红光-PDT治疗疗效优于绿光-PDT,复发率低,而不良反应两者相似;两次光照治疗方案与单次光照治疗的疗效无明显差异,但前者疼痛明显。     

维生素C增强氧化砷联用二甲萘醌诱导的U937细胞凋亡及其机制

目的 探讨维生素C是否可增强三氧化二砷（As2O3）联用二甲萘醌（DMNQ）对白血病细胞株U937的促凋亡效应及其机制。方法 以As2O3、维生素C、DMNQ不同组合孵育细胞，采用流式细胞仪及电镜检测细胞凋亡，并设立各种对照。结果 维生素C可增加As2O3联用DMNQ（10μmol/L）诱导U937细胞发生凋亡的比例（不加和加用维生素C细胞凋亡率分别为35.24%和61.20%）；过氧化氢酶可逆转这一效应；维生素C对DMNQ（20μmol/L）单独诱导U937细胞凋亡无影响。结论 维生素C在As2O3存在的情况下，通过活性氧依赖的途径，促进U937细胞凋亡。     

原子力声显微镜评价超声靶向微泡破坏法对大鼠心肌母细胞的影响

目的 探讨运用原子力声显微镜评价超声靶向微泡破坏法对大鼠心肌母细胞(H9C2)影响的可行性.方法 采用不同超声参数对H9C2细胞进行辐照处理.使用原子力声显微镜观察细胞骨架、形态结构的改变;采用台盼蓝染色法及荧光物质转入法检测细胞存活率及细胞膜通透性变化.结果 (1)通过比较辐照后H9C2细胞生存率及发光率变化,适宜参数为:频率1 MHz,声强1.0 W/cm2,占空比20％,辐照时间60 s;(2)原子力声显微镜可以完整显示H9C2细胞的形态结构,以形态像、声学像及三维像的差异区分细胞损伤的程度.结论 原子力声显微镜能够准确评估不同超声辐照参数对H9C2细胞的影响,优化超声靶向微泡破坏法转染参数.     

Examining and analyzing subcellular morphology of renal tissue treated by histotripsy

Our recent studies have shown that high-intensity pulsed ultrasound can achieve mechanical tissue fragmentation, a process we call histotripsy. Histotripsy has many medical applications where noninvasive tissue removal or significant tissue disruption is needed (e.g., cancer therapy). The primary aim of this study is to investigate tissue regions treated by histotripsy and to characterize the boundary between the treated and untreated zones using transmission electron microscopy (TEM). The nature of the tissue disruption suggests many clinical applications and provides insights on the physical mechanism of histotripsy. Fresh ex vivo porcine kidney tissues were treated using histotripsy. A 1 MHz 100 mm diameter focused transducer was used to deliver 15 cycle histotripsy pulses at a peak negative pressure of 17 MPa and a pulse repetition frequency (PRF) of 100 Hz. Each lesion was produced by a 3 × 3 (lateral) × 4 (axial) grid with 2 mm between adjacent lateral and 3 mm between axial exposure points using mechanical scanning. Two thousand pulses were applied to each exposure point to achieve tissue fragmentation. After treatment, the tissue was processed and examined using TEM. Extensive fragmentation of the tissues treated with histotripsy was achieved. TEM micrographs of the tissue treated by histotripsy, showing no recognizable cellular features and little recognizable subcellular structures, demonstrates the efficacy of this technique in ablating the targeted tissue regions. A boundary, or transition zone, of a few microns separated the affected and unaffected areas, demonstrating the precision of histotripsy tissue targeting. TEM micrographs of the tissue treated by histotripsy showed no discernable cellular structure within the treated region. Histotripsy can minimize fragmentation of the adjoining nontargeted tissues because, as a nonlinear threshold phenomenon, damage can be highly localized. The potential for high lesion precision is evident in the TEM micrographs. (E-mail: fwinterr@umich.edu)     

Polymer-Based Materials in Cancer Treatment: From Therapeutic Carrier and Ultrasound Contrast Agent to Theranostic Applications

The emergence of theranostics with ultrasound technology is a promising development, as it opens pathways to providing more effective treatments for cancer. Advancements in ultrasound imaging would give a more detailed and accurate image for better diagnosis and treatment planning. Polymeric ultrasound contrast agents (UCAs) are appealing because they are stable and easily modified for active targeting. In addition, a better therapy could be achieved in conjunction with advancements in UCAs. The active targeting not only makes the precise imaging possible, but also leads to targeted delivery of active components to specific local treatment sites. A polymeric nanocarrier with surface bioconjugation is the key to prolonging the bioavailability of the encapsulated drugs or genes and the capacity to target the specific tumor site. Using ultrasound with other imaging modalities will open more precise and better ways for diagnosis and therapy and bring us a step closer to personalized medicine. This review focuses on polymer-based materials of UCAs, multimodal imaging agents and therapeutic carriers that have been currently explored for their theranostic applications involving ultrasound for cancer diagnosis and treatment.     

三种抗癌剂诱导肿瘤细胞凋亡与活性氧产生关系的研究

目的 探讨抗癌剂、活性氧、凋亡三者之间的关系,从而进一步探讨抗癌剂的作用及肿瘤细胞耐药机制以及活性氧在肿瘤发生上的意义。方法 用足叶乙甙（Vp16）、阿霉素（ADR）、顺铂（DDP0作用于K562细胞,用流式细胞仪检测三种抗癌剂在不同浓度、作用24h对K562细胞活性氧产生的影响及对凋亡的影响。同时用形态学方法观察凋亡细胞的形态改变。结果 ①Vp16、ADR、DDP三种抗癌剂均可通过激发K562细胞产生活性氧来诱导该细胞发生凋亡;②每种抗癌剂激发K562细胞产生活性氧及诱发该细胞凋亡各有其最适浓度(Vp16为5μg/ml,ADR为3μg/ml,DDP为μg/ml）及最佳作用时间（24h）。结论 流式细胞仪（FCM）测定细胞内活性氧产生状态及细胞凋亡情况,方法具有敏感、快速、简便、只需微量血、可除去坏死细胞碎片等优点。可用于抗癌剂的筛选,指导临床用药及选择敏感抗癌剂的有效剂量及最佳时间,并为探索治疗肿瘤新方法提供一个思路。     

黄芪三七合剂对大鼠肾缺血再灌注损伤的作用及机制研究

目的观察黄芪三七合剂（A＆R）对肾缺血再灌注损伤（IRI）大鼠血液活性氧（ROS）变化的影响,探讨其抗IRI损伤的机制。方法雄性Sprague．Dawley（sD）大鼠30只,随机分为正常组（n=5）、假手术组（SG）（n=5）和IRl24h组（n=10）,A＆R组（n=10）。造模：采用微血管夹夹闭双侧肾蒂,22vain后松开动脉夹,用5／0尼龙缝合线缝合腹部。再灌注24h后将小鼠行麻醉处死。A＆R组给予A＆R（3mL／d）,假手术组及IRI24h组给予同等体积的生理盐水。采用全自动生化分析仪检测各组大鼠的肾功能,苏木精-伊红染色了解肾脏病理损害,流式细胞仪检测红细胞ROS。结果IRI24h组和A＆R组肾小管出现不同程度的管腔扩张、变性与坏死,间质炎性细胞浸润、充血水肿等变化。IRI后24h时,IRI24h组、A＆R组血清尿素氮（BUN）和肌酐（Cr）均高于假手术组、正常组,差异有统计学意义（P〈0．05）;A＆R组ROS荧光强度阳性率显著低于IRI24h组,差异有统计学意义（P〈O．05）。A＆R组肾小管损伤评分明显低IRI24h组（P〈0．05）。相关性分析发现,红细胞ROS荧光强度阳性率与’肾小管损伤评分、肌酐、尿素氮水平成正相关（r=0．917,P〈0．01;r=0．897,P〈0．01;r=0．896,P〈0．01）。结论A＆R对肾脏缺血再灌注损伤具有明显的保护作用,其机制可能为抑制血液中ROS的活性,从而抑制氧化应激对肾脏的损伤。     

Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells

Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c-jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time–PCR, TRAF2, ASK1 and c-jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c-jun were elevated in MG-132 treated cells. Giving ROS scavenger N-acetyl-L-cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation.     

强直性脊柱炎光波浴治疗及康复护理

目的：改善强直性脊柱炎引起的功能障碍,延缓其病情发展。方法：用光波浴及水疗配合康复护理治疗强直性脊柱炎。结果：６０例中临床治愈３例,占２１．７％;显效３２例,占５３．３％;有效１５例,占２５％;总有效率１００％。结论：该疗法能缓解疼痛,改善关节活动度,调节机体免疫,延缓病情发展,无毒副作用。     

The effect of hypoxemic resuscitationfrom hemorrhagic shock on blood pressure restoration and on oxidative and inflammatory responses

OBJECTIVE: We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the standard strategy. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit. SUBJECTS: Thirty-one New Zealand white rabbits weighting 3.1-3.4[Symbol: see text]kg INTERVENTIONS: Anesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40[Symbol: see text]mmHg for 60[Symbol: see text]min. Resuscitation was performed by reinfusing the shed blood for 30[Symbol: see text]min under normoxemia (PaO(2) 95-105[Symbol: see text]mmHg, control group, n[Symbol: see text]=[Symbol: see text]10) or hypoxemia (PaO(2) 35-40[Symbol: see text]mmHg, hypox-res group, n[Symbol: see text]=[Symbol: see text]10); Ringer's lactate was given from 30 to 60[Symbol: see text]min to restore arterial pressure within baseline values. A sham group was assigned (n[Symbol: see text]=[Symbol: see text]11). Animals were recorded for 120[Symbol: see text]min postresuscitation and for further 360[Symbol: see text]min to assess the early mortality rate. MEASUREMENTS AND RESULTS: Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in mortality rate. CONCLUSIONS: Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.