Alveolar recruitment prevents rapid-reperfusion-induced injury of lung transplants.

BACKGROUND: Physical factors play an important role in ischemia-reperfusion-induced injury of lung transplants. For example, rapid restoration of reperfusion resulted in severe pulmonary edema and deterioration of pulmonary function of lung explants in an ex vivo reperfusion system. This type of injury can be prevented by a stepwise increase in the perfusion flow rate, or by adding prostaglandin E1 (PGE1) to the blood perfusate during the first 10 minutes. However, the mechanisms of these protective effects are unknown. We noted a dramatic decrease in airway pressure rather than pulmonary arterial pressure in these studies, suggesting that lung recruitment may be an important factor in minimizing injury. METHODS: In the present study, we examined the importance of alveolar recruitment in preventing rapid-reperfusion-induced lung injury. Rat lungs were flushed preserved with low potassium dextran solution for 12 hours at 4 degrees C. Lung explants were randomly divided into three groups: 1) untreated control; 2) lungs inflated to total lung capacity for 2 minutes; and 3) lungs ventilated for 10 minutes prior to reperfusion. Postpreservation lung function was assessed in an isolated rat lung reperfusion model. RESULTS: Rapid initiation of reperfusion led to severe pulmonary edema and significant pulmonary dysfunction. In inflation or ventilation groups, the injury was significantly attenuated. The PaO2 and shunt fractions in these lungs were comparable to normal lungs. A significant drop in airway pressure was observed in these two groups and the lung compliance in the inflation group was significantly better than other two groups. CONCLUSIONS: These results suggest that overcoming alveolar collapse with inflation or ventilation, may protect the lung from mechanical-stress-induced injury during reperfusion.     

Extracellular thioredoxin levels are increased in patients with acute lung injury

BACKGROUND: Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult. METHODS: Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n=30) and healthy controls (n=18, plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores. RESULTS: BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin. CONCLUSIONS: Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.     

Management of transfusion-related acute lung injury with extracorporeal cardiopulmonary support in a four-year-old child

We report a case of successful management of transfusion-relatedacute lung injury (TRALI) with prolonged cardiopulmonary bypasssupport in a 4-yr-old patient undergoing elective cardiac surgery.TRALI was diagnosed clinically and immunologically by detectionof reactive antibodies in a unit of fresh frozen plasma thathad been administered to the patient. The aetiology and managementof TRALI are briefly discussed and possible implications ofthis case for the management of TRALI are highlighted. Br J Anaesth 2003; 91: 292–4     

Small dose of exogenous surfactant combined with partial liquid ventilation in experimental acute lung injury: effects on gas exchange, haemodynamics, lung mechanics, and lung pathology

A combination of exogenous surfactant and partial liquid ventilation(PLV) with perfluorocarbons should enhance gas exchange, improverespiratory mechanics and reduce tissue damage of the lung inacute lung injury (ALI). We used a small dose of exogenous surfactantwith and without PLV in an experimental model of ALI and studiedthe effects on gas exchange, haemodynamics, lung mechanics,and lung pathology. ALI was induced by repeated lavages (Pa_O2/FI_O2less than 13 kPa) in 24 anaesthesized, tracheotomized and mechanicallyventilated (FI_O2 1.0) juvenile pigs. They were treated randomlywith either a single intratracheal dose of surfactant (50 mgkg^–1, Curosurf^®, Serono AG, München, Germany)(SURF-group, n=8), a single intratracheal dose of surfactant(50 mg kg^–1, Curosurf^®) followed by PLV with 30 mlkg^–1 of perfluorocarbon (PF 5080, 3M, Germany) (SURF-PLV-group,n=8) or no further intervention (controls, n=8). Pulmonary gasexchange, respiratory mechanics, and haemodynamics were measuredhourly for a 6 h period. In the SURF-group, the intrapulmonaryright-to-left shunt (Q^·S/Q^·T) decreased significantlyfrom mean 51 (SEM 5)% after lavage to 12 (2)%, and Pa_O2 increasedsignificantly from 8.1 (0.7) to 61.2 (4.7) kPa compared withcontrols and compared with the SURF-PLV-group (P<0.05). Inthe SURF-PLV-group, Q^·S/Q^·T decreased significantlyfrom 54 (3)% after induction of ALI to 26 (3)% and Pa_O2 increasedsignificantly from 7.2 (0.5) to 30.8 (5.0) kPa compared withcontrols (P<0.05). Static compliance of the respiratory system(C_RS), significantly improved in the SURF-PLV-group comparedwith controls (P<0.05). Upon histological examination, theSURF-group revealed the lowest total injury score compared withcontrols and the SURF-PLV-group (P<0.05). We conclude thatin this experimental model of ALI, treatment with a small doseof exogenous surfactant improves pulmonary gas exchange andreduces the lung injury more effectively than the combined treatmentof a small dose of exogenous surfactant and PLV. Br J Anaesth 2001; 87: 593–601     

血管外肺水指数与氧合指数评估急性肺损伤程度准确性的比较

目的 比较血管外肺水指数(EVLWI)与氧合指数(PaO2/FiO2)评估急性肺损伤(ALI)程度的准确性.方法 创伤后(创伤时间＜48 h)ALI行机械通气患者16例,性别不限,年龄18～80岁,采用PiCCO监测仪监测EVLWI,建立PiCCO监测后每隔24 h采集动脉血样,测定PaO2,计算PaO2/FiO2;同时记录EVLWI,并进行肺损伤评分(LIS).分别在建立HCCO监测后24、48、72 h时按PaO2/FiO2将患者分为PaO2/FiO2≤300组(200 mm Hg＜PaO2/FiO2≤300 mm Hg)和PaO2/FiO2≤200组(PaO2/FiO2≤200 mm Hg),按EVLWI将患者分为EVLWI＜10组(EVLWI＜10 ml/kg)和EVLWI≥10组(EVLWI≥10 ml/kg).结果 与PaO2/FiO2≤300组比较,PaO2/FiO2≤200组建立PiCCO监测后24、48 h时LIS评分差异无统计学意义(P＞0.05),建立PiCCO监测后72 h时LIS评分升高(P＜0.01).与EVLWI＜10组比较,EVLWI≥10组各时点LIS评分均升高(P＜0.05或0.01).结论 临床中PaO2/FiO2作为评估ALI程度的指标存在局限性,而EVLWI在评估ALI程度方面可能比PaO2/FiO2更准确.

Abstract：

Objective To compare extravascular lung water index (EVLWI) and oxygenation index (PaO2/FiO2) in estimation of acute lung injury(ALI) .Methods Sixteen patients with post traumatic ALI (within 48 h) of both sexes, aged 18-80 yr, were studied. The patients were mechanically ventilated. Right internal jugular vein and femoral artery were catheterized and connected to PiCCO monitor (IntelliVue MP50, Philips, Netherlands).EVLWI was monitored with the PiCCO system. PaO2 was determined every 24 h. ALI was diagnosed based on the following criteria:(1)PaO2/FiO2≤300 mm Hg; (2)X-ray chest film-patchy shadows in the bilateral lungs and (3) CVP≤12 mm Hg.Lung injury score(LIS) was recorded. The patients were divided into PaO2/FiO2≤ 300 group and ≤200 group and EVLWI ≥ 10 group and ＜ 10 group. Results There was no significant difference in LIS between PaO2/FiO2 ≤300 group and PaO2/FiO2 ≤200 group at 24 and 48 h of PiCCO monitoring. At 72 h of PiCCO monitoring LIS was significantly increased in PaO2/FiO2 ≤200 group as compared with PaO2/FiO2 ≤300 group, LIS was significantly higher in EVLWI≥ 10 group than in EVLWI ＜ 10 group at 24, 48 and 72 h of PiCCO monitoring. Conclusion EVLWI is more accurate than PaO2 /FiO2 in estimation of severity of ALI.     

Prone positioning ventilation for treatment of acute lung injury and acute respiratory distress syndrome

Patients who are diagnosed with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) usually have ventilation-perfusion mismatch, severe decrease in lung capacity, and gas exchange abnormalities. Health care work-ers have implemented various strategies in an attempt to compensate for these pathological alterations. By rotating patients with ALI/ARDS between the supine and prone position, it is possible to achieve a significant improvement in PaO2/FiO2, decrease shunting and therefore improve oxy-genation without use of expensive, invasive and experimen-tal procedures.     

新型感染性腹膜炎与急性肺损伤动物模型的建立

目的建立一种稳定的上消化道穿孔后由化学性腹膜炎到感染性腹膜炎的动物模型，探讨其在急性肺损伤中的作用。方法48只大鼠分2组，假手术组（A组），实验组（B组）横断十二指肠球部1／2，并将胃窦部下拉悬吊于中腹部。术后6、12h分批处死，统计各组的造模成功率；随机取A组各时间点8只，B组各时间点造模成功大鼠8只，进行血WBC，血、腹水内毒素测定，呼吸频率计数，动脉血气分析，肺湿／干比，肺组织病理损害评分和电镜观察。结果A组造模成功率为0，B组造模成功率为91．7％（22／24）。B组各时间点血内毒素、腹水内毒素、血WBC、呼吸频率、肺湿／干比、肺组织损害评分、PaCO2均显著高于A组（P〈0．01），PaO2低于A组（P〈0．01）；B组6h血内毒素、腹水内毒素及血WBC、呼吸频率、肺组织损害评分、湿／干比均显著低于12h（P〈0．01）。结论该动物模型接近临床，可以模拟上消化道穿孔后由化学性腹膜炎到感染性腹膜炎的过程，并可导致急性肺损伤。     

血管生成素-1在急性肺损伤治疗中的作用

急性肺损伤(acute lung injury,ALI)的典型特征是肺泡毛细血管的损伤以及伴随而来的肺水肿,血管生成素-1(angiopoietin-1,Ang1)可以减轻炎症反应,抑制内皮细胞凋亡及降低血管通透性,因此能通过减小肺泡毛细血管的损伤而在肺损伤治疗中发挥一定的作用并已在动物实验中得到证实.进一步认识并了解Ang1可能为肺损伤的预防及治疗提供一种新的手段.现就Ang1的功能及其在ALI预防与治疗中的进展作一综述.     

乌司他丁联合奥曲肽对重症急性胰腺炎患者炎症风暴和肺损伤的作用及机制

目的 探讨乌司他丁联合奥曲肽对重症急性胰腺炎(SAP)患者炎症风暴和肺损伤的影响及其机制研究.方法 前瞻性选择2016年1月至2019年12月西安交通大学第二附属医院收治的60例SAP患者为研究对象,采用随机数字表法分为对照组和干预组,每组30例.对照组给予包括奥曲肽在内的常规治疗,干预组在对照组的基础上联合应用乌司他...     

高CO2血症在急性肺损伤治疗中的相关机制

高CO2血症是肺保护性通气策略的一个重要组成部分。临床证据支持了容许性高CO2血症在急性肺损伤／急性呼吸窘迫综合征（ALI／ARDS）患者中的应用。动物实验也证明治疗性高CO2血症可减轻缺血／再灌注、机械通气、内毒素所致的肺损伤。高CO2血症可在多个方面影响ALI／ARDS的病理生理,免疫功能及细胞分子水平的变化。     

Cardiovascular responses to high-frequency oscillatory ventilation during acute lung injury in sheep

Purpose The present study was designed to evaluate pulmonary and systemic hemodynamics and blood gas changes on switching from conventional mechanical ventilation (CMV) to high-frequency oscillatory ventilation (HFOV) in a large animal model of acute lung injury. Methods Eleven anesthetised sheep chronically instrumented with vascular monitoring were prepared. Animals received oleic acid (0.08 ml·kg⁻¹) intravenously and were ventilated for 4 h h after the administration of oleic acid. The animals were then randomized into the two following different ventilation modes: CMV (tidal volume [V_T], 6 ml·kg⁻¹; respiratory rate [RR], 25 · min⁻¹) with positive end-expiratory pressure (PEEP) of 12 cmH₂O; or CMV under the same settings without PEEP. HFOV was then switched. The setting of mean airway pressure with a fixed stroke volume was changed between 25, 18, and 12 cmH₂O every 20 min. Mean pulmonary artery pressure, pulmonary artery occlusive pressure (Paop), left atrium pressure, systemic arterial pressure, cardiac output (CO), and blood gas composition under each setting were measured before and after HFOV. Results Switching to HFOV, from without PEEP, resulted in significant increases in Paop and PaO2 and a decrease in CO at higher (25, 18 cmH₂O) mean airway pressure. However, when changed from low V_T and PEEP, HFOV produced further improvements in oxygenation without any deterioration of cardiovascular depression. Thus, switching to HFOV from CMV with low V_T and high PEEP may have little influence on pulmonary or systemic hemodynamics in acute lung injury. Conclusion We conclude that hemodynamic responses are dependent on the predefined setting of PEEP during CMV, and on applied mean airway pressure during HFOV.     

输血相关性急性肺损伤一例

输血相关性急性肺损伤(transfusion-related acute lung injury,TRALI)指发生在输血过程中或输血后6h内出现的缺氧或双侧肺水肿,排除左房高压,排除循环超负荷并且输血前没有预先存在的急性肺损伤.报道l例女性患者,36岁,全麻术中发生TRALI,经治疗后患者康复出院.     

血管生成素-1在急性肺损伤治疗中的作用

急性肺损伤(acute lung injury,ALI)的典型特征是肺泡毛细血管的损伤以及伴随而来的肺水肿,血管生成素-1(angiopoietin-1,Ang1)可以减轻炎症反应,抑制内皮细胞凋亡及降低血管通透性,因此能通过减小肺泡毛细血管的损伤而在肺损伤治疗中发挥一定的作用并已在动物实验中得到证实.进一步认识并了解Ang1可能为肺损伤的预防及治疗提供一种新的手段.现就Ang1的功能及其在ALI预防与治疗中的进展作一综述.     

肺复张结合肺保护通气对肝移植术后肺损伤换气功能的影响

目的探讨肺复张结合肺保护通气策略对肝移植术后ALI或ARDS早期换气功能、血流动力学的影响。方法肝移植术后合并ALI者18例，其中6例发展为ARDS，给予25cm H2O气道压力及PEEP 17 cm H2O通气2min，扩张已萎陷实变的肺泡，并用适当的PEEP预防肺泡闭塞，保持肺泡复张。结果18例病人肺复张后氧分压、氧饱和度及吸氧分数均有明显改善，除1例肺部严重感染病人肺复张后吸氧分数仅上升40％，余17例均对肺复张反应良好。复张后平均氧分压上升68mmHg，平均氧饱和度上升9．5％，平均吸氧分数上升104．66％，改善的氧合可维持2～24h。肺复张结合肺保护通气策略纠正低氧血症的有效率为94．4％。病人对肺复张的耐受性佳，无明显并发症。结论肺复张结合肺保护通气策略是治疗肝移植术后ALI或ARDS的安全有效措施。     

中性粒细胞死亡在急性肺损伤中的作用

急性肺损伤（acute lung injury, ALI）是临床常见的危重病,严重时会发展成急性呼吸窘迫综合征,甚至导致死亡,目前尚无有效的治疗方法。在不同病理生理条件下,中性粒细胞呈现多种不同的死亡形式,如中性粒细胞外诱捕网、铁死亡、焦亡、凋亡、自噬、坏死及坏死性凋亡等。不同形式的中性粒细胞死亡在ALI的发生、发展进...     

Alveolar recruitment strategy improves arterial oxygenation after cardiopulmonary bypass

Atelectasis occurs during general anaesthesia. This is partly responsible for the impairment of gas exchange that occurs peri-operatively. During cardiopulmonary bypass, this atelectasis is exacerbated by the physical collapse of the lungs. As a result, poor arterial oxygenation is often seen postoperatively. We tested the effect of an 'alveolar recruitment strategy' on arterial oxygenation in a prospective randomised study of 78 patients undergoing cardiopulmonary bypass. Patients were divided equally into three groups of 26. Group 'no PEEP' received a standard post bypass manual lung inflation, and no positive end-expiratory pressure was applied until arrival at intensive care unit. Group '5 PEEP' received a standard post bypass manual inflation, and then 5 cmH2O of positive end-expiratory pressure was applied and maintained until extubation on intensive care. The third group, 'recruitment group', received a pressure-controlled stepwise increase in positive end-expiratory pressure up to 15 cmH2O and tidal volumes of up to 18 ml x kg(-1) until a peak inspiratory pressure of 40 cmH2O was reached. This was maintained for 10 cycles; the positive end-expiratory pressure of 5 cmH2O was maintained until extubation on intensive care. There was a significantly better oxygenation in the recruitment group at 30 min and 1 h post bypass when compared with the no PEEP and 5 PEEP groups. There was no significant difference in any of the groups beyond 1 h. Application of 5 cmH2O positive end-expiratory pressure alone had no significant effect on oxygenation. No complications due to the alveolar recruitment manoeuvre occurred. We conclude that the application of an alveolar recruitment strategy improves arterial oxygenation after cardiopulmonary bypass surgery.     

Effects of penehyclidine hydrochloride on apoptosis of lung tissues in rats with traumatic acute lung injury

Objective： To investigate the effects ofpenehyclidine hydrochloride on apoptosis of lung tissue cells and its mechanism in acute lung injury following blunt chest trauma in rats. Methods： Sprague Dawley （SD） rats （n=54） weighing （250-25） g were divided equally and randomly into three groups： normal control group （C group, n= 18）, trauma model group （T group, n= 18） and penehyclidine hydrochloride treatment group （P group, n=18）. Each group was further divided into three subgroups according to the time points of 3, 12 and 24 hours after experiment （at each time point, n=6 for each subgroup）. Rats of P group were intraperitoneally injected with penehyclidine hydrochloride for 2 mg/kg immediately after blunt chest trauma and rats in its 24 hours subgroup were once again injected with penehyclidine hy- drochloride in the same dose 12 hours after injury. Lung tissue samples were collected at every time point and cell apoptosis in lung tissues were measured by TUNEL. Apoptotic index （AI） was calculated, expressions of bax and bcl-2 were detected by immunohistochemical staining of SABC, and lung tissue sections were taken for light and electron microscopic observation. Results： As compared with C group, at every time point, AI and expressions ofbax and bcl-2 in T group were higher （P〈0.05）, and the ratio of bcl-2/bax markedly decreased （P〈0.05）, especially in the 24 hours subgroup. The ratio in T group （0.468±0.007） was lower than that in C group （1.382±0.058, t=12.5, P〈0.01）. Lung tissue injuries were significant under a light microscope, and the number of apoptotic cells increased obviously under a transmission electron microscope. As compared with T group at the same phase, AI and expression of bax decreased in P group （P〈0.05 and P〈0.01）, while the expression of bcl-2 increased significantly （P〈0.01）, and the ratio of bcl-2/bax markedly increased （P〈0.05）, especially in the 24 hours subgroup. The ratio in P group （1.012-0.070） was much higher than that in T group （0.468±0.007, t=-8.3, P〈0.01）. The injury of lung tissues was relieved, and apoptosis of cells decreased obviously under a transmission electron microscopic observation. Conclusions： Apoptosis and expressions ofbax and bcl-2 in lung tissues might be involved in the pathogenesis of lung injury induced by blunt chest trauma. Penehyclidine hydrochloride can alleviate lung injuries by inhibiting apoptosis of lung tissue cells, during which effects ofpenehyclidine hydrochloride on regulating expressions ofbax and bcl-2 may play an important role.     

急性肺损伤中线粒体动力学变化

背景 急性肺损伤(acute lung injury,ALI)病因复杂,病情发展迅速,死亡率高,是临床常见的急危重症. 目的 探讨ALI时线粒体动力学变化及影响因素. 内容 ALI时线粒体融合减少及分裂增加,致线粒体片段化,功能失调.线粒体动力学的这些改变与体内活性氧(reactive oxygen species,ROS)生成过多、炎症因子过度释放及细胞凋亡等有关. 趋向 随着ALI时线粒体动力学变化机制的不断深入研究,可望为ALI的治疗提供新思路.     

吸入米力农对油酸诱导大鼠急性肺损伤的影响

目的观察雾化吸入米力农对油酸诱导大鼠急性肺损伤(ALI)的影响。方法采用静脉注射油酸复制ALI大鼠模型。将20只SD大鼠随机分为两组:米力农雾化吸入治疗组(治疗组)和油酸诱导ALI组(对照组)。实验过程中每隔60min记录大鼠BP、肺动脉压(PAP)、气道压(Paw),并且检验动脉血气和混合静脉血气。注射油酸240min后检测支气管肺泡灌洗液(BALF)蛋白定量(TP)、白细胞计数及分类,测定肺湿干比(W/D)、肿瘤坏死因子α(TNF-α)浓度,并且对肺组织进行光镜和电镜观察。结果与对照组比较,治疗组PAP[(9.5±1.3)vs.(12.6±1.3)mmHg],Paw[(6.2±0.8)vs.(7.5±0.8)mmHg],肺内分流率[(13.5±3.3)%vs.(18.8±4.1)%]和氧合指数(PaO2/FiO2)[(300±26)vs.(226±17)mmHg]均明显改善,而治疗组TP[(0.55±0.07)vs.(0.71±0.1)g/L],白细胞计数[(0.66±0.1)vs.(1.11±0.09)×106/L]和分类[(29.4±3.1)%vs.(36.6±3.7)%],肺W/D[(6.2±0.4)vs.(7.2±0.4)],TNF-α[(213.7±11.5)vs.(296.3±15.7)ng/L)]均明显低于对照组(P<0.05)。光镜和电镜观察治疗组肺组织水肿以及板层小体脱颗粒现象得到明显改善。结论米力农雾化吸入能够缓解油酸引起的ALI。     

血管内皮细胞生长因子在急性肺损伤中的作用

急性肺损伤(acute lurg injury,ALI)和急性呼吸窘迫综合征(acute respiratory distressyndrome,ARDS)的特征性病理改变为肺毛细血管通透性增高所致的肺水肿,血管内皮细胞生长因子能抗血管内皮细胞凋亡并增加血管通透性,可能在ALI和ARDS的病理过程中起到重要作用.现对血管内皮细胞生长因子在ALI中的作用进行综述,旨在为ALI和ARDS的治疗提供新的思路.