Role of thoracoscopy in acute management of chest injury

PURPOSE OF REVIEW: To review the literature on the use of video-assisted thoracoscopic surgery for the diagnosis and treatment of intrathoracic injuries. RECENT FINDINGS: Video-assisted thoracoscopic surgery is a relatively recent innovation. It was originally promoted for the treatment of retained hemothorax and the diagnosis of diaphragm injury. It is highly effective for the management of those problems. Recent studies have focused on video-assisted thoracoscopic surgery for treatment of chest wall bleeding, diagnosis of transmediastinal injuries, pericardial window and persistent pneumothorax. In properly selected patients, video-assisted thoracoscopic surgery is extremely efficacious in managing these problems. SUMMARY: The role of video-assisted thoracoscopic surgery in the management of acute chest injury is expanding. It is an invaluable tool for the trauma surgeon.     

Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

Introduction

This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury.

Methods

Twenty-one sheep (37 ± 2 kg) were operatively prepared for chronic study and randomly allocated to either the sham, control, or rhAPC group (n = 7 each). The control and rhAPC groups were subjected to insufflation of four sets of 12 breaths of cotton smoke followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. Healthy sham animals were not subjected to the injury and received only four sets of 12 breaths of room air and instillation of the vehicle (normal saline). rhAPC (24 μg/kg/hour) was intravenously administered from 1 hour post injury until the end of the 24-hour experiment. Regional microvascular blood flow was analyzed using colored microspheres. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution to maintain hematocrit at baseline levels.

Results

The rhAPC-associated reduction in heart malondialdehyde (MDA) and heart 3-nitrotyrosine (a reliable indicator of tissue injury) levels occurred parallel to a significant increase in mean arterial pressure and to a significant reduction in heart rate and cardiac output compared with untreated controls that showed a typical hypotensive, hyperdynamic response to the injury (P < 0.05). In addition, rhAPC significantly attenuated the changes in microvascular blood flow to the trachea, kidney, and spleen compared with untreated controls (P < 0.05 each). Blood flow to the ileum and pancreas, however, remained similar between groups. The cerebral blood flow as measured in cerebral cortex, cerebellum, thalamus, pons, and hypothalamus, was significantly increased in untreated controls, due to a loss of cerebral autoregulation in septic shock. rhAPC stabilized cerebral blood flow at baseline levels, as in the sham group.

Conclusions

We conclude that rhAPC stabilized cardiovascular functions and attenuated the changes in visceral and cerebral microcirculation in sheep suffering from ALI and septic shock by reduction of cardiac MDA and 3-nitrotyrosine.     

The chest wall in acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: There has recently been renewed interest in the chest wall during mechanical ventilation, related to lung-protective ventilation strategies, as well as in the role of abdominal pressure in many facets of critical illness. The purpose of this review is to address relevant issues related to the chest wall and mechanical ventilation, particularly in patients with acute lung injury/acute respiratory distress syndrome. RECENT FINDINGS: In mechanically ventilated patients with acute lung injury, intra-abdominal pressure is an important determinant of chest wall compliance. With elevated intra-abdominal pressure, the compliance of the chest wall and total respiratory system is decreased, with a relatively normal compliance of the lungs. The lung compression effects of increased intra-abdominal pressure may lead to a loss of lung volume with atelectasis. An appropriate level of positive end-expiratory pressure is necessary to counterbalance this collapsing effect on the lungs. Also, the stiff chest wall results in a lower transpulmonary pressure during positive-pressure ventilation. SUMMARY: As chest wall compliance may have important clinical implications during positive-pressure ventilation, the physiology of this effect should be considered, particularly in patients with acute lung injury and increased abdominal pressure.     

Divergent effects of activated neutrophils on inflammation, Kupffer cell/splenocyte activation, and lung injury following blunt chest trauma

Polymorphonuclear granulocytes (PMNs) have been attributed a primarily deleterious role in the pathogenesis of acute lung injury (ALI). However, evidence exists that PMNs might also act beneficially in certain types of ALI. In this regard, we investigated the role of activated neutrophils in the pathophysiology of lung contusion-induced ALI. We used the model of blunt chest trauma accompanied by PMN-depletion in male C3H/HeN mice. Animals received 25 μg/g body weight PMN-depleting antibody Gr-1 intravenously 48 h before trauma. Bronchoalveolar lavage (BAL) and lung tissue interleukin 6 (IL-6) were similarly elevated in PMN-depleted and control animals after trauma, whereas macrophage inflammatory protein 2 and monocyte chemoattractant protein 1 in BAL and lungs, IL-10 in BAL, and lung keratinocyte chemoattractant (KC) were even further increased in the absence of PMNs. Plasma IL-6 and KC were also increased in response to the insult and even further in the absence of PMNs. Chest trauma induced an enhanced release of IL-6, tumor necrosis factor α, macrophage inflammatory protein 2, monocyte chemoattractant protein 1, and IL-10 from isolated KU, which was blunted in the absence of PMNs. In the presence of PMNs, BAL protein was further increased at 30 h when compared with the 3-h time point, which was not the case in the absence of PMNs. Taken together, in response to lung trauma, activated neutrophils control inflammation including mediator release from distant immune cells but simultaneously mediate pulmonary tissue damage. Thus, keeping in mind potential inflammatory adverse effects, modulation of neutrophil activation or trafficking might be a reasonable therapeutic approach in chest trauma-induced lung injury.     

外源性肺表面活性物质治疗脓毒性急性肺损伤的机制研究

目的;观察外源性肺表面活性物质早期治疗对脓毒性急性肺损伤的疗铲及对内源性ＰＳ的影响。方法：实验动物在机械通气下建立脓毒性ＡＬＩ模型,早期气管内稍许主有机提取的ＰＳ１００ｍｇ／ｋｇ,连续治疗６小时,观察氧合指数,肺内分流,肺动脉顺应性的变化;并对支气管肺泡灌洗液磷脂含量和表面张力进行分析。用Ｗｅｓｔｅｒｎ ｄｏｔ ｂｌｏｔ法测定ＰＳ特异性结合蛋白含量,用Ｎｏｒｔｈｅｒｎ ｂｌｏｔ法测定ＳＰ－ＡｍＲＮ     

多巴酚丁胺对脓毒症休克兔急性肺损伤的影响

目的 探讨不同剂量多巴酚丁胺对脓毒症休克兔急性肺损伤(acute lung injury,ALI)的保护作用及其可能机制.方法 采用盲肠结扎穿孔联合静脉注射内毒素制备脓毒症休克模型,将70只新西兰雄性大白兔随机(随机数字法)均分为假手术组(A组)、ALI模型组(B组)、多巴酚丁胺低剂量组(C组)、多巴酚丁胺中剂量组(D组)和多巴酚丁胺高剂量组(E组),分别于造模后3h和6h点处死,留取肺组织标本.ELISA法检测环磷酸腺苷(cyclicadenosine monophosphate,cAMP)浓度;Western-blot法检测水通道蛋白5(Aquaporin 5,AQP5)蛋白浓度;计算肺湿/干重(wet to dry weight,W/D)比值;光镜和电镜下观察各组小鼠肺组织病理学改变,并对肺组织病理损伤进行评分.多组间差异比较采用单因素方差分析,组间两两比较采用LSD法.结果 与A组相比,B组cAMP、AQP5蛋白浓度在3h及6h明显降低(3.53±0.43)pmol/mL vs.(21.18±0.62)pmol/mL; (0.44±0.04)pmol/mLvs.(0.99 ±0.06)pmol/mL;(2.71 ±0.56) pmol/mL vs.(21.78±0.62) pmol/mL; (0.29±0.05) pmol/mLvs.(0.91±0.06) pmol/mL;P＜0.001,W/D比值则明显升高P＜0.00.与B组相比,C组cAMP及AQP5蛋白水平在6h明显增加(8.48±0.61) pmol/mLvs.(2.71 ±0.56) pmol/mL,P＜0.001; (0.49 ±0.04)pmol/mLvs.(0.29±0.05) pmol/mL,(P=0.001),D、E组cAMP及AQP5蛋白水平在3h、6h明显增加(10.86±0.66) pmol/mLvs.(3.53±0.43) pmol/mL;(0.60 ±0.05) pmol/mLvs.(0.44±0.04) pmol/mL; (13.80 ±0.49) pmol/mLvs.(2.71 ±0.56) pmol/mL; (0.64 ±0.03) pmol/mLvs.(0.29±0.05) pmol/mL; (15.57 ±0.60) pmol/mLvs.(3.53±0.43) pmol/mL; (0.91 ±0.05)pmol/mLvs.(0.44±0.04)pmol/mL; (19.30±0.42)pmol/mLvs.(2.71±0.56)pmol/mL;(0.89±0.08) pmol/mLvs.(0.29±0.05)pmol/mL;P＜0.01,E组W/D比值明显降低(P=0.002;P=0.001).与C、D组相比,E组cAMP及AQP5水平在3h、6h均有所增加(P＜0.01).光镜及电镜下,B组肺的病理形态及超微结构损伤均较重,肺病理学评分明显升高(P＜0.01);多巴酚丁胺干预后,肺的病理形态及超微结构损伤有所减轻,肺组织病理学评分明显降低(P＜0.01).结论 多巴酚丁胺对内毒素诱导的急性肺损伤有一定程度保护作用,其机制可能与提高肺组织cAMP水平,上调AQP5蛋白表达量有关,且大剂量多巴酚丁胺效果更佳.     

Mediators of septic lung injury

Septic pulmonary injury remains a significant cause of morbidity and mortality among hospitalized patients today and is likely to increase in prevalence as advances in medical technology allow the salvage of more critically ill and immunocompromised hosts. Treatment of the host's underlying disease and even of the infection itself has appeared to redeem septic patients only to have them succumb in increasing numbers to the pulmonary injury reaction. Our understanding of the mechanisms and mediators of lung dysfunction in sepsis is in a rapidly expanding phase. Currently we recognize the contributions of several blood elements, lipids, and peptides to pulmonary injury, although the relative importance and points of interaction and interdependence of these mediators remain to be established. It is hoped that a more complete understanding of the process of pulmonary injury in sepsis will suggest effective means of intervention at a stage in which damage may be reversed or minimized.     

还原型谷胱甘肽对脓毒症大鼠急性肺损伤的干预作用

目的探讨还原型谷胱甘肽（GSH）对脓毒症大鼠急性肺损伤（ALI）的干预作用。方法将72只雄性SD大鼠随机分为假手术组、模型组、干预组,每组各24只。干预组及模型组采用改良盲肠结扎穿孔法建立脓毒症ALI大鼠模型,假手术组建立假手术模型。术后30min,干预组予腹腔内注射GSH250mg／kg,同时间模型组和假手术组予等量生理盐水。每组大鼠平均分为4个亚组,分别于术后6、12、24和48h杀活取材。检测动脉血氧分压（PaO2）、血清C反应蛋白（CRP）、肺组织湿干重比（W/D）及肺组织丙二醛（MDA）、GSH浓度,并观察肺组织的病理改变。结果模型组PaO2及GSH含量明显低于假手术组和干预组（P均〈0．05）,且随时间延长而降低。模型组CRP水平、W／D及MDA含量均高于假手术组与干预组（P均〈0．05）,CRP值术后12h时最高,而后逐步下降。另外,与模型组比,干预组病理切片所示肺损伤程度较轻。结论GSH能抑制脓毒症ALI大鼠的炎症反应、减少氧化应激损伤,进而减轻ALI程度。     

Acute lung injury in septic shock

Over the past 20 years, substantial information has been gained concerning sepsis-associated ALI. Although the mortality from ARDS remains unchanged, the spectrum of disease has altered. Patients rarely die acutely from the direct sequelae of ALI, including hypoxemia, but most commonly demonstrate a protracted clinical course that eventuates in MSOF. Further, with improved resuscitation of medical and surgical emergencies, the profile of patients who develop ARDS has changed and now reflects an older and more complex patient. While the pathophysiology and mediators of tissue injury in septic ARDS is now better understood, effective therapeutic interventions have not yet resulted from early multicenter trials. It is clear from the recent multicenter trials on the effects of methylprednisolone dose that apparently useful therapies in animal models must undergo this form of investigation before widespread clinical dissemination. Without an effective and singular "golden bullet" for the treatment of the varied presentation of ARDS, it remains our contention that basic management principles of ARDS must continue to emphasize an aggressive approach to the identification and treatment of the septic focus while all efforts are concurrently exploited to reduce the potentially aggravating effects of secondary injury on microvascular function. Currently research into the diagnosis, prevention, and treatment of nosocomial pneumonia is an example of how secondary injury may be minimized in ALI. Further, it is important to recognize the potentially detrimental effects of various therapies on the microvascular membrane in ARDS.     

Role of platelet-activating factor in pneumolysin-induced acute lung injury

OBJECTIVE: Acute respiratory failure is a major complication of severe pneumococcal pneumonia, characterized by impairment of pulmonary microvascular barrier function and pulmonary hypertension. Both features can be evoked by pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae. We hypothesized that platelet-activating factor (PAF) and associated downstream signaling pathways play a role in the PLY-induced development of acute lung injury. DESIGN: Controlled, ex vivo laboratory study. SUBJECTS: Female Balb/C mice, 8-12 wks old. INTERVENTIONS: Ventilated and blood-free-perfused lungs of wild-type and PAF receptor-deficient mice were challenged with recombinant PLY. MEASUREMENTS AND MAIN RESULTS: Intravascular PLY, but not the pneumolysoid Pd-B (PLY with a Trp-Phe substitution at position 433), caused an impressive dose-dependent increase in pulmonary vascular resistance and increased PAF in lung homogenates, as detected by reversed-phase high-performance liquid chromatography coupled to tandem mass spectrometry. The pressor response was reduced in lungs of PAF receptor-deficient mice and after PAF receptor blockade by BN 50730. PLY and exogenous PAF increased thromboxane B2 in lung effluate, and thromboxane receptor inhibition by BM 13505 diminished the pressor response to PLY. Differential inhibition of intracellular signaling steps suggested significant contribution of phosphatidylcholine-specific phospholipase C and protein kinase C and of the Rho/Rho-kinase pathway to PLY-induced pulmonary vasoconstriction. Unrelated to the pulmonary arterial pressor response, microvascular leakage of PLY was diminished in lungs of PAF receptor-deficient mice as well. CONCLUSIONS: PAF significantly contributed to PLY-induced acute injury in murine lungs. The PAF-mediated pressor response to PLY depends on thromboxane and on the downstream effectors phosphatidylcholine-specific phospholipase C, protein kinase C, and Rho-kinase.     

TLR4在脓毒症大鼠急性肺损伤中作用

目的:研究Toll样受体(Toll like receptors,TLR)4在脓毒症急性肺损伤(acute lung injury,ALI)大鼠肺内的动态表达情况.方法:32只Wistar大鼠随机分成对照组12只与ALI组20只.实验6,12,18,24 h后分别处死大鼠.采用Real-time PCR测定肺组织TLR4 mRNA表达,免疫组织化学观察肺组织TLR4蛋白的表达情况.结果:ALI组与对照组比较,肺组织TLR4蛋白和TLR4 mRNA表达增加(P<0.01).ALI组TLR4蛋白和TLR4 mRNA在盲肠结扎穿孔术术后逐渐增加至18 h达高峰,后逐渐下降.结论:TLR4升高与脓毒症ALI的发生、发展密切相关.     

吸入一氧化氮治疗脓毒性肺损伤对肺表面活性物质影响的研究

目的：研究吸入一氧化氮（ＮＯ）治疗脓毒性急性肺损伤（ＡＬＩ）时对内源性肺表面活性物质（ＰＳ）的影响。方法：机械通气条件下制作吸入ＮＯ治疗ＡＬＩ的兔模型,观察ＮＯ的疗效,测定内源性ＰＳ系统总磷脂（ＴＰＬ）,饱和磷脂（ＤＳＰＣ）含量,小与大聚集体比例（ＳＡ／ＬＡ）,Ｗｅｓｔｅｒｎ ｄｏｔ ｂｌｏｔ法测定肺表面活性物质结合蛋白－Ａ（ＳＰ－Ａ）含量及Ｎｏｒｔｈｅｒｎ ｂｌｏｔ法测ＳＰ－Ａ ｍＲＮＡ含量的变     

急性肺损伤家兔早期中性粒细胞相关功能的变化研究

目的　研究白细胞介素 8(IL 8)、中性粒细胞黏附功能与急性肺损伤 (AL I)的关系。方法　 18只雄性新西兰家兔随机分为两组 :对照组 8只 ,AL I组 10只。建立内毒素 AL I模型。测定两组动物血气、血常规、中性粒细胞 CD11b表达强度、血清 IL 8和丙二醛浓度 ,并进行肺组织病理学观察。结果　 AL I组动物注射内毒素后出现血压降低、心率减慢、p H进行性下降。给药后 3h外周血中性粒细胞下降明显 ,6 h有不同程度的上升 ;中性粒细胞表面 CD11b表达强度与血清 IL 8、丙二醛浓度呈进行性上升 ,均较对照组差异显著(P均 <0 .0 5 )。模型动物肺组织炎性粒细胞浸润明显 ,弥漫性肺泡隔增厚 ,灶性出血和纤维蛋白渗出。给药后相关分析显示 :6 h时 CD11b与 IL 8呈明显相关 (决定系数 r2 =0 .813,回归方程 Y=2 6 .72 9X ) ;肺组织病理改变严重程度评分与 CD11b表达强度亦呈明显相关 (决定系数 r2 =0 .771,回归方程 Y=0 .0 110 2 X 5 .2 92 )。结论　内毒素可以诱导产生大量 IL 8,使中性粒细胞表面 CD11b的表达被快速激活并上调 ,并与 IL 8和肺组织病理改变评分之间呈高度相关。 IL 8和 CD11b均是 AL I早期较为敏感的诊断指标之一     

巨噬细胞移动抑制因子在急性肺损伤中的作用

巨噬细胞移动抑制因子(MIF)是一个重要的宿主防御中介物,通过引起细胞因子、趋化因子以及氧自由基等炎性介质级联释放,使促炎和抗炎失衡促进急性肺损伤(ALI)的发生、发展.MIF还具有免疫调节功能,能调节和平衡ALI 时局部和全身炎性反应和免疫紊乱,参与肺组织内的防御反应.目前MIF对ALI 促炎反应以及免疫调节的机制尚不清楚.研究发现MIF与ALI/ARDS 肺损伤的严重程度及疾病的预后相关,现查阅近年有关MIF在ALI中的基础研究及临床相关文献,对MIF在ALI中的作用进行综述.     

Acute lung injury and acute respiratory distress syndrome in sepsis and septic shock

Sepsis remains the leading cause of ARDS, and ARDS is still an often fatal condition. With our expanding knowledge of the pathobiologic mechanisms and the relationship between these two entities, early recognition, treatment, and prevention of sepsis may prevent or hasten recovery from ARDS. Understanding the biologic markers involved in the complex inflammatory response of sepsis and acute lung injury offers the possibility of future investigations to target treatment based on these mediators.     

中性粒细胞凋亡在大鼠急性肺损伤发病机制中的意义

目的从细胞凋亡的角度探讨急性肺损伤(ALI)的发病机制。方法雄性SD大鼠36只,随机分为模型组(ALI组)30只和正常对照组6只,观察肺组织病理切片,进行肺损伤评分(LIS)、肺水含量测定、肺通透性测定(LPI)、肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)测定、BALF中性粒细胞(PMN)凋亡测定。结果模型组可见肺泡腔狭窄、炎性细胞渗出等ALI表现,且随时程延长病变加重。模型组各时相肺损伤评分较对照组有显著性差异(P均<0·05),随时程延长肺损伤评分逐渐增加。模型组各时相点肺湿干重比较对照组明显升高(P均<0·05),但各时相点之间无差异。模型组LPI2、4h与对照组无差异,6、8、16h显著升高(P均<0·01)。模型组2hBALF中TNF-α达高峰(P<0·01),4、6h与对照组有显著差异(P均<0·05),8、16h与对照组组无差异。BALF中PMN凋亡结果,模型组各时相点均低于对照组(P均<0·01)。结论PMN在肺泡内的凋亡在ALI的发生发展中起重要作用。ALI时BALF中PMN凋亡率呈下降的趋势,总体低于正常值。     

Urinary biomarkers in septic acute kidney injury

Objective To appraise the literature on the value of urinary biomarkers in septic acute kidney injury (AKI). Design Systematic review. Setting Academic medical centre. Patients and participants Human studies of urinary biomarkers. Interventions None. Measurements and results Fourteen articles fulfilled inclusion criteria. Most studies were small, single-centre, and included mixed medical/surgical adult populations. Few focused solely on septic AKI and all had notable limitations. Retrieved articles included data on low-molecular-weight proteins (β₂-microglobulin, α₁-microglobulin, adenosine deaminase binding protein, retinol binding protein, cystatin C, renal tubular epithelial antigen-1), enzymes (N-acetyl-β-glucosaminidase, alanine-aminopeptidase, alkaline phosphatase; lactate dehydrogenase, α/π-glutathione-S-transferase, γ-glutamyl transpeptidase), cytokines [platelet activating factor (PAF), interleukin-18 (IL-18)] and other biomarkers [kidney injury molecule-1, Na/H exchanger isoform-3 (NHE3)]. Increased PAF, IL-18, and NHE3 were detected early in septic AKI and preceded overt kidney failure. Several additional biomarkers were evident early in AKI; however, their diagnostic value in sepsis remains unknown. In one study, IL-18 excretion was higher in septic than in non-septic AKI. IL-18 also predicted deterioration in kidney function, with increased values preceding clinically significant kidney failure by 24–48 h. Detection of cystatin C, α₁-microglobulin, and IL-18 predicted need for renal replacement therapy (RRT). Conclusions Few clinical studies of urinary biomarkers in AKI have included septic patients. However, there is promising evidence that selected biomarkers may aid in the early detection of AKI in sepsis and may have value for predicting subsequent deterioration in kidney function. Additional prospective studies are needed to accurately describe their diagnostic and prognostic value in septic AKI.     

Role of tumor necrosis factor in sepsis and acute lung injury

TNF is a small protein secreted by activated monocytes and macrophages that mediates the in vivo effects of endotoxin. When injected into experimental animals, TNF reproduces the picture of septic or endotoxin shock. In addition, antibodies to TNF protect animals against the deleterious effects of IV injections of either LPS or live bacteria. Specifically, the available evidence suggests that TNF may be necessary for the organ injury and failure seen in sepsis. However, TNF probably is not the final common pathway to shock and tissue injury. Inhibition of cyclooxygenase is protective from the lethal effects of both LPS and TNF infusion, suggesting that prostanoids play an important, and perhaps more proximal role in the generation of tissue injury. In addition, TNF is produced and cleared from the blood-stream within a short period of time after an LPS stimulus, suggesting that TNF sets into motion a chain of events that may be self-perpetuating even in the absence of further TNF stimulus. In the near future, the treatment of sepsis may involve the administration of antibodies both to TNF and to LPS. Cyclooxygenase inhibitors should also begin to play a role in the therapy of sepsis. In the more distant future it is likely that we will be able to manipulate the state of activation of genes that code for TNF to exert some control over its production and secretion. It is perhaps within our grasp to finally reduce the morbidity and mortality of this lethal condition.     

雌激素在百草枯中毒致急性肺损伤及肺纤维化中的作用

百草枯中毒导致的急性肺损伤(ALI)及肺纤维化主要发病机制是氧化应激和肺泡Ⅱ型细胞凋亡.线粒体是凋亡的决定性环节,也是细胞内氧化应激的源头.雌激素是一类有广泛生物活性的甾体激素,在其受体的介导下,在各种发育和生理过程中有着广泛的作用.近年来,发现雌激素对肺损伤有明确的保护作用,而雌激素的保护作用与线粒体的功能调节有着密切联系.线粒体可能是雌激素发挥细胞保护作用的重要靶标.本文将对雌激素在肺损伤及肺纤维化中的作用作一综述.