肺复张策略对急性呼吸窘迫综合征模型犬压力-容积曲线和肺组织病理的影响

 目的：探讨肺复张策略（LRM）对急性呼吸窘迫综合征（ARDS）模型犬静态P-V曲线和肺组织病理的影响。方法：健康犬24只,随机分为肺外源性ARDS（ARDSexp）组和肺内源性ARDS（ARDSp）组,每组12只,经股静脉注射油酸复制ARDSexp模型,盐酸灌肺复制ARDSp模型,再随机各分为2组,每组6只,分别采用肺保护通气策略（LPVS）和LPVS联合以压力-容积曲线为导向的LRM（LPVS+LRM）进行机械通气。LRM采用压力控制通气（PCV）,压力上限为高位转折点（UIP）, 呼气末正压(PEEP)为低位转折点（LIP）+2 cmH₂O,维持时间60 s。观察LRM后P-V曲线LIP、UIP以及肺复张容积变化。4 h后取肺组织行病理学评分。结果：应用LRM后,ARDSp组和ARDSexp组LIP均明显降低,与ARDSp组相比,ARDSexp组LIP下降更为显著;ARDSexp组4例犬P-V曲线出现UIP消失,2例无改变,ARDSp组犬UIP无明显变化;肺复张容积增加,肺病理损伤评分明显下降,ARDSp组的改善程度不如ARDSexp组。结论：LRM可降低LIP,导致P-V曲线发生改变,LRM后应重新根据P-V曲线调整呼吸机通气参数;对于不同原因ARDS,LRM具有增加肺复张容积、减轻肺损伤的作用,ARDSexp组的治疗效果明显优于ARDSp组。     

Morphometric differences in pulmonary lesions in primary and secondary ARDS. A preliminary study in autopsies

The present study was undertaken in order to describe the morphological differences between pulmonary lesions in acute respiratory distress syndrome originating from direct pulmonary injury (ARDSp) and those originating from extrapulmonary injury (ARDSexp).We investigated a total of 38 ARDS-patients (27 males) ranging in age from 19 to 75 years, classified according to underlying disease in pulmonary (ARDSp) and extrapulmonary disease (ARDSexp). The extent of acute diffuse alveolar damage was assessed morphometrically on histologic gross sections in the upper and lower lobes of one lung.The lesions showed quantitative differences in extent and distribution according to underlying disease (primary pulmonary or secondary involvement).In pulmonary ARDS, a predominance of alveolar collapse (16.6% ± 12.3% versus 10.3% ± 11.9%, p = 0,03), fibrinous exudate (1.7% ± 3.2% versus 0.4% ± 1.1%, p = 0.01) and alveolar wall edema (11.2% ± 7.4% versus 6.6% ± 4.4%, p = 0,05) were found compared to extrapulmonary ARDS.We conclude that the morphology of acute diffuse alveolar damage (DAD) is mainly determined by underlying disease (pulmonary ARDS or extrapulmonary ARDS) differing in quantitative terms within the lung. Physiological, radiographic and respiratory system mechanics differences described in ARDSp and ARDSexp may therefore be due to morphometric differences in pulmonary lesions.     

肺复张对肺内、外源性ARDS模型犬氧代谢和血流动力学的影响

目的: 探讨肺复张对肺内、外源性急性呼吸窘迫综合征(ARDS)模型犬氧代谢和血流动力学的影响。方法: 健康杂种犬12只,随机分为肺外源性ARDS(ARDSexp)组和肺内源性ARDS(ARDSp)组,每组6只。股静脉注射油酸复制ARDSexp模型,盐酸灌肺复制ARDSp模型。制模成功后,行机械通气,采用肺保护通气策略(LPVS)并给予1次肺复张(RM)。RM采用压力控制通气(PCV),压力上限为高位转折点(UIP), 呼气末正压(PEEP)为低位转折点(LIP)+2 cmH₂O, 维持时间60 s,RM后继续原方案通气。观察不同阶段氧代谢指标和血流动力学的变化。结果: RM后两组动脉血氧分压(PaO₂)、静脉血氧分压(PvO₂) 、混合静脉血氧饱和度(SvO₂)和氧输送量(DO₂)明显升高,氧摄取率(ERO₂) 逐渐降低;ARDSexp组的PaO₂、PvO₂、SvO₂和DO₂高于ARDSp组,ERO₂则低于ARDSp组。RM时两组平均肺动脉压(MPAP)、中心静脉压(CVP)、肺动脉嵌压(PAWP)均显著增加,ARDSp组与ARDSexp组相比较无显著性差异,但RM结束后两组均逐渐恢复至基础水平。RM时两组平均动脉压(MAP)和心脏指数(CI)下降,但很快恢复至基础水平,ARDSp组下降幅度更为显著。结论: RM可以提高氧输送和改善组织缺氧,ARDSexp组的效果优于ARDSp组;RM对血液动力学会造成短暂的影响,ARDSp组受到的影响大于ARDSexp组。     

Postoperative adult respiratory distress syndrome: the Howard experience.

To describe the natural history of adult respiratory distress syndrome (ARDS), we compared the clinical course of two groups of postoperative critically ill patients who developed respiratory failure requiring prolonged endotracheal intubation (minimum: 4 days). The two groups with ARDS (Group 1) and without ARDS (Group 2) were compared for the following clinical parameters: PO2/FIO2 ratio, cardiac index, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance, pulmonary compliance, serial chest radiograph findings, presence or absence of sepsis, oxygen transport parameters, morbidity, and mortality. Twenty patients are described over a 9-month period ending in March 1990-10 patients in each group. Characteristic differences between the two groups in terms of oxygen consumption, pulmonary compliance, pulmonary vascular resistance, numbers of organ systems failing, and mortality were noted. Our experience supports the recommendations of early institution of positive and expiratory pressure and optimizing oxygen delivery parameters in the management of ARDS.     

正压通气下呼吸道气阻与顺应性在线测算方法改进

:目的 采用气道正压对患者进行通气治疗,实现对通气患者呼吸道气阻(resistance, R)和顺应性(compliance, C)在线测算。 方法 当呼气末气流为 0 时,在呼气支持压(expiratory positive airway pressure, EPAP)之上叠加 1 个负 脉冲气压,使肺内气压在该脉冲期间高于体外气压,从而向外泄放气流,并对该泄放气流进行处理来测算 R 和 C。 然 后以正常成人、典型急性呼吸窘迫综合征( acute respiratory distress syndrome, ARDS) 患者和慢性阻塞性肺疾病 (chronic obstructive pulmonary disease, COPD)患者为实验对象,建立仿真实验平台,进行仿真实验来测算 R 和 C。 结 果 所测算的正常成人 R 和 C 误差分别为 3. 398% 和-3. 288% ,COPD 患者 R 和 C 误差分别为 1. 265% 和-1. 348% , ARDS 患者 R 和 C 误差分别为 3. 400% 和-3. 286% 。 结论 气道正压通气下,采用呼气末叠加 1 个负脉冲气压在 EPAP 上来测算 R 和 C 的方法具有良好的可行性,研究结果为智能调控通气、精准通气等技术打下坚实基础。     

大承气汤治疗大鼠内毒素性ARDS的疗效分析及免疫调节机制研究

目的： 探讨大承气汤对内毒素“二次打击”致急性呼吸窘迫综合征（ARDS）的防治作用,为中西医结合防治呼吸道疾病提供有效依据。方法: 48只健康雄性Wistar大鼠随机分为4组:生理盐水对照组、ARDS模型组、大承气汤治疗组、地塞米松治疗组,每组12只。采用大肠杆菌脂多糖(LPS) “二次打击”建立大鼠ARDS动物模型,结合动脉血气分析、肺湿/干重(W／D)比值及肺组织病理学观察和评分,评价大承气汤的药理作用;酶联免疫吸附法（ELISA）测定血浆与支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、IL-10水平,探讨大承气汤的药理作用和免疫调节机制。结果: (1)大承气汤可以显著提高ARDS大鼠动脉血氧分压,增加血氧饱和度,降低肺湿/干重比值和肺病理损伤,减轻肺水肿和肺部炎症反应,因而具有改善肺通气、抑制肺部炎症反应、减轻肺损伤功能。(2)大承气汤可使血浆促炎细胞因子（TNF-α、IL-1）和抗炎细胞因子（IL-10）水平同时降低,使BALF中TNF-α、IL-1水平降低同时IL-10水平却升高,因而表现出对全身炎症反应和局部炎症反应不同的免疫调节机能。结论: 大承气汤抑制肺部炎症反应除与下调全身炎症反应水平有关,同时还与促进肺部抗炎介质产生、调节肺部促炎介质/抗炎介质的平衡有关。     

肺血管内皮细胞分泌功能的改变与急性肺损伤/急性呼吸窘迫综合征

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)是临床上常见的急危重症,病死率高达25%~45%,治疗上主要限于器官功能与全身支持治疗,尤其是呼吸支持治疗,“等待”肺损伤的缓解。在ARDS发病机制中肺血管内皮细胞(pulmonary vascular endothelial cell,PVEC)既是受损的主要靶细胞,更是活跃的炎症和效应细胞,血管内皮细胞(vascular endothelial cell,VEC)的激活和损伤程度与ARDS预后密切相关。本文将主要阐述ALI/ARDS发病机制中PVEC部分分泌功能的改变。     

Intratracheal Administration of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Patient with Acute Respiratory Distress Syndrome

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) have been introduced as a possible therapy in acute lung injury and acute respiratory distress syndrome (ARDS). This case history is reported of a 59-yr-old man who was treated with MSCs in the course of ARDS and subsequent pulmonary fibrosis. He received a long period of mechanical ventilation and weaning proved difficult. On hospital day 114, he underwent the intratracheal administration of UCB-derived MSCs at a dose of 1 × 10⁶/kg. After cell infusion, an immediate improvement was shown in his mental status, his lung compliance (from 22.7 mL/cmH₂O to 27.9 mL/cmH₂O), PaO₂/FiO₂ ratio (from 191 mmHg to 334 mmHg) and his chest radiography over the course of three days. Even though he finally died of repeated pulmonary infection, our current findings suggest the possibility of using MSCs therapy in an ARDS patient. It is the first clinical case of UCB-derived MSCs therapy ever reported.     

SARS-CoV virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues.

These studies attempt to understand more fully the host response and pathogenesis associated with severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) by monitoring gene expression using formalin-fixed paraffin-embedded (FFPE) pulmonary autopsy tissues. These tissues were from patients in different hospitals in Singapore who were diagnosed with various microbial infections, including SARS-CoV, that caused acute respiratory distress syndrome (ARDS). Global expression patterns showed limited correlation between end-stage ARDS and the initiating pathogen, but when focusing on a subset of genes implicated in pulmonary pathogenesis, molecular signatures of pulmonary disease were obtained and appeared to be influenced by preexisting pulmonary complications and also bacterial components of infection. Many factors detected during pulmonary damage and repair, such as extracellular matrix (ECM) components, transforming growth factor (TGF) enhancers, acute-phase proteins, and antioxidants, were included in the molecular profiles of these ARDS lung tissues. In addition, differential expression of cytokines within these pulmonary tissues were observed, including notable genes involved in the interferon (IFN) pathway, such as Stat1, IFN regulatory factor-1 (IRF-1), interleukin-6 (IL-6), IL-8, and IL-18, that are often characterized as elevated in ARDS patients.     

早期无创正压通气对重症急性胰腺炎合并肺损伤的保护作用机制

重症急性胰腺炎（SAP）所致急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）是SAP早期死亡的主要原因,是肺外型 ARDS 的典型代表,已有研究证实早期无创正压通气对 SAP所致 ARDS是一种行之有效治疗方法。本文主要就早期无创正压通气对重症急性胰腺炎合并肺损伤的保护作用及其作用机制研究情况进行综述,为早期无创正压通气用于重症急性胰腺炎合并肺损伤治疗提供依据。     

Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS

ARDS (acute respiratory distress syndrome) can be associated with septic shock and multiple organ failure caused by an uncontrolled systemic inflammatory response to Gram-negative bacterial infection. While in animal models the key role of the endothelial adhesion molecules ICAM-1, E-selectin, and VCAM in ARDS has been extensively studied, there are scarcely any corresponding pathomorphological studies of human lung tissue. Hence, little is known about whether there is a comparable, or even heterogeneous, expression pattern of these molecules in the human pulmonary vasculature. This study was therefore undertaken to investigate the immunohistochemical expression of the constitutively expressed PECAM (CD31) and the inducible molecules ICAM-1, E-selectin, and VCAM in ARDS lungs from patients who had died in septic shock induced by Gram-negative bacteria. While in all specimens (ARDS and normal lungs) there was homogeneous strong expression of PECAM in all vessels, ICAM-1 was clearly up-regulated in ARDS lungs. E-selectin and VCAM were not expressed by endothelial cells (ECs) in normal lungs, but in ARDS lungs there was strong expression of both molecules in larger vessels, while in the capillaries there was only mosaic-like weak expression of a few ECs. This immunohistochemical investigation demonstrates the induction and up-regulation of adhesion molecules in human ARDS lungs, comparable to that described in animal models. There is also markedly heterogeneous expression of E-selectin and VCAM, indicating toporegional differences in the function of pulmonary ECs.     

Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome. Angiotensin-converting enzyme (ACE) and its effector peptide angiotensin (Ang) II have been implicated in the pathogenesis of ARDS. A counter-regulatory enzyme of ACE, ie ACE2 that degrades Ang II to Ang-(1-7), offers a promising novel treatment modality for this syndrome. As the involvement of ACE and ACE2 in ARDS is still unclear, this study investigated the role of these two enzymes in an animal model of ARDS. ARDS was induced in rats by intratracheal administration of LPS followed by mechanical ventilation. During ventilation, animals were treated with saline (placebo), losartan (Ang II receptor antagonist), or with a protease-resistant, cyclic form of Ang-(1-7) [cAng-(1-7)]. In bronchoalveolar lavage fluid (BALF) of ventilated LPS-exposed animals, ACE activity was enhanced, whereas ACE2 activity was reduced. This was matched by enhanced BALF levels of Ang II and reduced levels of Ang-(1-7). Therapeutic intervention with cAng-(1-7) attenuated the inflammatory mediator response, markedly decreased lung injury scores, and improved lung function, as evidenced by increased oxygenation. These data indicate that ARDS develops, in part, due to reduced pulmonary levels of Ang-(1-7) and that repletion of this peptide halts the development of ARDS.     

慢性酗酒与急性肺损伤/急性呼吸窘迫综合征

急性肺损伤/急性呼吸窘迫综合征(acute lung injury/accute respiratory distress syndrome,ALI/ARDS)是在非心源性疾病过程中.     

Alveolar surfactant and adult respiratory distress syndrome

Summary The adult respiratory distress syndrome (ARDS) is characterized by extended inflammatory processes in the lung microvascular, interstitial, and alveolar compartments, resulting in vasomotor disturbances, plasma leakage, cell injury, and complex gas exchange disturbances. Abnormalities in the alveolar surfactant system have long been implicated in the pathogenetic sequelae of this life-threatening syndrome. This hypothesis is supported by similarities in pulmonary failure between patients with ARDS and preterm babies with infant respiratory distress syndrome, known to be triggered primarily by lack of surfactant material. Mechanisms of surfactant alterations in ARDS include: (a) lack of surface-active compounds (phospholipids, apoproteins) due to reduced generation/release by diseased pneumocytes or to increased loss of material (this feature includes changes in the relative composition of the surfactant phospholipid and/or apoprotein profiles); (b) inhibition of surfactant function by plasma protein leakage (inhibitory potencies of different plasma proteins have been defined); (c) incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin upon hyaline membrane formation; and (d) damage/inhibition of surfactant compounds by inflammatory mediators (proteases, oxidants, nonsurfactant lipids). Alterations in alveolar surfactant function may well contribute to a variety of pathophysiological key events encountered in ARDS. These include decrease in compliance, ventilation-perfusion mismatch including shunt flow due to altered gas flow distribution (atelectasis, partial alveolar collapse, small airway collapse), and lung edema formation. Moreover, more speculative at the present time, surfactant abnormalities may add to a reduction in alveolar host defense competence and an upregulation of inflammatory events under conditions of ARDS. Persistent atelectasis of surfactant-deficient and in particular fibrin-loaded alveoli may represent a key event to trigger fibroblast proliferation and fibrosis in late ARDS (collapse induration). Overall, the presently available data on surfactant abnormalities in ARDS lend credit to therapeutic trials with transbronchial surfactant administration. In addition to the classical goals of replacement therapy defined for preterm infants (rapid improvement in lung compliance and gas exchange), this approach will have to consider its impact on host defense competence and inflammatory and proliferative processes when applied in adults with respiratory failure.Abbreviations ARDS adult respiratory distress syndrome - IRDS infant respiratory distrss syndrome - PC phosphatidylcholine - PG phosphatidylglycerol - PE phosphatidylethanolamine - PS phosphatidylserine - PI phosphatidylinositol - Sph spingomyelin - BAL bronchoalveolar lavage - TNF tumor necrosis factor Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Architectural remodelling in acute and chronic interstitial lung disease: fibrosis or fibroelastosis?

AIMS: Pulmonary fibrosis in acute and chronic lung disease has been much investigated, but little attention has been directed at the elastic tissue in these situations. Our aim was to verify whether elastic deposition accompanies collagen deposition in the repairing process of acute and chronic lung injury. METHODS AND RESULTS: We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides sampled from autopsied lungs, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: I, 10 normal patients; II, 10 patients with cardiogenic pulmonary oedema; III, 23 adult respiratory distress syndrome (ARDS) patients in the early phase; IV, 14 ARDS patients in the late fibroproliferative phase; and V, 10 idiopathic pulmonary fibrosis patients. The first two groups were used as controls. The content of fibres of the collagenous and elastic systems was significantly increased in groups IV and V as compared to the other groups. CONCLUSIONS: Our results indicate that deposition of elastic system fibres is present in the fibroproliferative phase of ARDS and in usual interstitial pneumonia and suggest that this event may contribute to the alveolar mechanical dysfunction and remodelling that occur in acute and chronic interstitial lung disease.     

凝血和纤溶失衡在急性肺损伤中的作用

急性肺损伤(acute lung injury,ALI),以肺泡上皮细胞和血管内皮屏障损伤、急性炎症反应、富含蛋白的肺水肿为特征,是一种临床常见的危重病症,可进一步发展为急性呼吸窘迫综合症(acute respiratory distress syndrome,ARDS).     

Pressure controlled inverse ratio ventilation in acute respiratory distress syndrome patients

Appropriate ventilatory intervention is life saving in acute respiratory distress syndrome (ARDS). Pressure controlled inverse ratio ventilation (PC-IRV) is the likely mode of ventilation benefiting in extreme conditions of ARDS. However, guidelines when to start PC-IRV is not yet well defined. The ventilation-related dilemma, which we faced in two illustrative cases of ARDS are presented. The first patient presenting clinically with ARDS but with high peak airway pressure (PIP) and low dynamic lung compliance, PC-IRV helped in reducing PIP, improved haemodynamics and the oxygenation of blood. In second patient with similar clinical presentation of ARDS, where although PIP was high but the dynamic compliance was better, the PC-IRV caused deterioration in PaO2. Here, patient rather did better with high PEEP (15 cm H2O) and usual I: E ratio (1:2). It is probable that the dynamic lung compliance (< 20ml/cmH2O), PIP (> 50 cm H2O) at conventional I: E ratio (1:2) ventilation (10 ml/kg) with hypotension might form the basis to develop a scoring system for guidance to switch over to PC-IRV ventilation. Further randomised prospective controlled clinical trials will then be required to establish indication to start PC-IRV in ARDS.     

Adult respiratory distress syndrome—a review

Adult respiratory distress syndrome (ARDS) represents a common pathway of damage to the lungs by a wide variety of different agents. The important aetiological factors and mechanisms of lung injury are considered. Electron microscopic features as well as light microscopy are described. Factors that may modify the pathological picture are discussed. Probably the most important of these is oxygen. This gas is said to produce interstitial pulmonary fibrosis but this concept is once again questioned.     

Regulatory T-cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide-induced acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) induces a strong local infiltration of regulatory T-cells (Tregs) in the lungs. However, at present, there remains a lack of adequate evidence showing the direct effect of Tregs on pulmonary repair and the related mechanisms of ARDS. Therefore, in this project, we studied the impact of Tregs on lipopolysaccharide (LPS)-induced ARDS and pulmonary inflammation. Surprisingly, we found that depletion of Tregs by injection of PC61 anti-CD25 antibody not only interfered with the inflammation resolution, such as inhibited total cell infiltration into the alveolar space, downregulated neutrophils, upregulated macrophages, but also impaired pulmonary epithelium and endothelial cell proliferation. Consistent with the attenuation of pulmonary repair, we found that the Th1 and Th17 immune responses were also impaired in Treg-depleted mice, suggesting that the presence of Tregs is vital for tissue repair, as Tregs modulate and promote the Th immune response in LPS-induced pulmonary inflammation.     

Pulmonary hypertension due to acute respiratory distress syndrome

Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients'' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO₂ was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit.