Risk factors for reperfusion injury after lung transplantation

Objective To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. Design and setting Retrospective study in the surgical intensive care unit (ICU) of a university hospital. Methods We collected data on 60 lung transplantation donor/recipient pairs from June 1993 to May 2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. Results The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48 h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p = 0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48 h after surgery (p = 0.014). The extubation was delayed (p = 0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p < 0.01). Conclusions Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigated. The preliminary results of the present study were presented at the 14th Annual Meeting of the European Society of Intensive Care Medicine, September 2001, Geneva, Switzerland     

Surfactant replacement in reperfusion injury after clinical lung transplantation

Background: Reperfusion injury remains a significant risk factor in the immediate postoperative course after lung transplantation. We report on our initial clinical experience of surfactant replacement in reperfusion injury after clinical lung transplantation. Methods and results: In 31 consecutive patients, lung (8 single lung, 16 bilateral lung) or heart-lung (7) transplantation was performed. In 6 patients, severe reperfusion injury developed and was treated with continuously nebulized surfactant. Compliance of the allograft increased 40 ± 25 % within 3 h following treatment with surfactant. Alveolar arterial oxygen gradient decreased by 23 ± 11 % after 3 h and by 35 ± 20 % after 6 h. Normal graft function was reestablished within 1–3 days after transplantation. All treated recipients were extubated until the 6th postoperative day. The 30-day mortality for the 31 recipients was 3.3 %, the 1-year survival 84 %. Conclusions: Surfactant replacement may become a clinical method for treatment of reperfusion injury after lung transplantation. Final revision received: 14 April 1999 Accepted: 23 April 1999     

Lipoxin A4 attenuates the lung ischaemia reperfusion injury in rats after lung transplantation

BackgroundLung ischaemia reperfusion injury (LIRI) is the major cause of primary lung dysfunction after lung transplantation. Lipoxin A4 inhibits the oxidative stress and inflammation. This study aimed to evaluate the potential protective effect of lipoxin A4 on LIRI in rats.MethodsSD (Sprague-Dawley) rats were randomised into the sham, LIRI and LA4 groups. Rats in the sham group received anaesthesia, thoracotomy and intravenous injection of saline, while those in the LIRI or LA4 group received left lung transplantation and intravenous injection of saline or lipoxin A4, respectively. After 24 h of reperfusion, the PaO₂/FiO₂ (Partial pressure of O2 to fraction inspiratory O2), wet/dry weight ratios and protein levels in lungs were measured to assess the alveolar capillary permeability. The oxidative stress response and inflammation were examined. The histological and apoptosis analyses of lung tissues were performed via HE staining (Haematoxylin-eosin staining) and TUNEL assay, respectively. The effects of lipoxin A4 on the endothelial viability and tube formation of hypoxaemia and reoxygenation-challenged rat pulmonary microvascular endothelium cells were determined.ResultsLipoxin A4 significantly ameliorated the alveolar capillary permeability, reduced the oxidative stress and inflammation in transplanted lungs. The histological injury and apoptosis of lung tissues were also alleviated by lipoxin A4. In vitro lipoxin A4 treatment promoted the endothelial tube formation and improved the endothelial viability.ConclusionLipoxin A4 protects LIRI after lung transplantation in rats, and its therapeutic effect is associated with the properties of anti-inflammation, anti-oxidation, and endothelium protection.

Key messages:

1. Lung transplantation is a treatment approach for the patients with lung disease.
2. LIRI is the major cause of postoperative primary lung dysfunction.
3. Lipoxins A4 exhibits strong anti-inflammatory properties.

     

肝移植术后急性肺损伤特点

目的:观察分析肝移植术后急性肺损伤发生原因及处理措施。方法:选择2000-02/2005-05在解放军总医院第二附属医院接受原位肝移植患者130例,均签署手术知情同意书。术毕给予呼吸机控制呼吸,自主呼吸恢复后给予呼吸机辅助呼吸,平均6.8h脱呼吸机,之后双鼻导管吸氧3~10L。定时测定血气分析、肝功能、肾功能、血常规、凝血4项、血乳酸、血氨、电解质及血糖,每日做痰、胆汁、腹腔引流液培养。防治细菌感染,预防真菌及病毒感染。进行抗排斥反应、保肝、营养代谢支持、利尿与扩血管等综合治疗。结果:①肝移植受者130例术后48h内死亡3例,术后3~10d内死亡9例均并发肺部感染,存活病例发生肺部感染28例。存活118例发生急性肺损伤87例(占73.7%),经治疗后各脏器均恢复正常。②患者发生急性肺损伤时间多为术后两三天,其中29例发生急性呼吸窘迫综合征,大部分经加大吸氧浓度或面罩吸氧,增加氧气雾化吸入次数等综合救治措施均恢复。③术中出血量为2000~8000mL者共76例,发生急性肺损伤69例;术中出血量>8000mL者18例,术后均出现急性肺损伤。急性肺损伤与术后出量(尿量、T管、腹腔引流)关系比较大。④原发病为肝炎肝硬化肝功能失代偿患者急性肺损伤的发病率最高,显著高于原发病为慢性肝炎肝硬化肝癌患者(85%,39%,P<0.05)。结论:肝移植术后急性肺损伤发生与原发疾病、手术损伤、术中血流动力学不稳定、术后出量有一定关系。临床除氧疗外,应做好全身综合治疗。     

缺血后处理对肺再灌注损伤中脂质过氧化反应的调整

目的:缺血后处理即在全面恢复再灌注前反复短暂多次预再灌、停灌,探讨缺血后处理对在体大鼠肺缺血再灌注损伤的脂质过氧化反应的影响。方法:实验于2004-05/06在汕头大学医学院附属肿瘤医院中心实验室完成。通过阻断左肺门建立大鼠在体左肺缺血再灌注模型,将24只健康雌性SD大鼠随机分为①假手术组8只:持续灌注105min。②缺血再灌注组8只:缺血45min,再灌注60min。③缺血后处理组8只:缺血45min后,短暂再灌注1min,缺血1min,反复5次,然后再全面恢复灌注60min。试验结束后处死动物,切取新鲜肺左叶组织制成100g/L组织匀浆,测定丙二醛含量用硫代巴比妥酸比色法,测定超氧化物歧化酶活性用黄嘌呤氧化酶法(羟胺法)。结果:3组24只动物均进入结果分析。①肺组织丙二醛含量测定结果:假手术组为(0.934±0.086)μmol/g,对照组为(1.230±0.169)μmol/g,缺血后处理组为(1.064±0.090)μmol/g,缺血后处理组与对照组相比明显降低(P<0.05)。②超氧化物歧化酶活性测定结果:假手术组为(2.838±0.509)μkat/g,对照组为(1.183±0.222)μkat/g,缺血后处理组为(2.008±0.298)μkat/g,缺血后处理组与对照组相比显著升高(P<0.01)。结论:对照组与假手术组相比,肺组织经历45min缺血60min再灌注后丙二醛含量明显升高,抗自由基酶类超氧化物歧化酶活性显著下降,说明再灌注期肺组织脂质过氧化反应增强,抗氧化能力降低。缺血后处理组较对照组肺组织中脂质代谢产物丙二醛含量下降,抗自由基酶超氧化物歧化酶活性增加,表明缺血后处理可减轻在体大鼠肺缺血再灌注损伤的脂质过氧化反应而产生肺保护作用。     

肾移植后的重症肺炎

背景：肾移植后重症肺炎发生率高,死亡率高,对其进行早期诊断及治疗具有重要意义。目的：分析呼吸重症监护室收治的肾移植后重症肺炎患者的临床特点、病情及预后,以提高其早期诊断率及治愈率。方法：对2004年1月至2012年9月郑州人民医院呼吸重症监护室收治的28例肾移植后出现重症肺炎的患者进行回顾性调查分析,总结其临床特点。应用急性生理学与慢性健康状况评分Ⅱ、英国胸科协会改良肺炎评分对患者病情进行评估,并给予适当的治疗。结果与结论：28例患者重症肺炎感染发生在肾移植后3-8个月,普遍应用免疫抑制剂的剂量较大;主诉有呼吸急促、干咳、胸闷、发热。血浆白蛋白下降明显,动脉血气分析均为低氧血症,低二氧化碳血症,动脉血氧饱和度进行性下降。胸部CT示肺部广泛渗出阴影。停用免疫抑制药物,并给予广谱抗感染药物、甲基泼尼松龙及无创呼吸机治疗后,治愈24例、好转2例、死亡2例。治疗期间患者肝、肾功能无恶化。提示肾移植后免疫抑制过度是并发重症肺炎的高危因素;重视体温监测,活动后气促及不明原因血清白蛋白下降有助于早期诊断。果断停用免疫抑制剂,并进行抗感染、甲基泼尼松龙及恰当无创呼吸机治疗是治疗成功的关键。     

缺血预处理联合缺血后处理对肺移植中缺血再灌注肺损伤的影响

背景:研究显示缺血预处理和缺血后处理在缺血再灌注肺损伤中均具有明显的保护作用。目的:观察缺血预处理联合缺血后处理对肺移植中缺血再灌注损伤的累积保护效应。方法:将40只SD大鼠随机等分为假手术组、模型组、缺血预处理组、缺血后处理组和联合处理组。后4组建立缺血再灌注肺损伤动物模型,缺血预处理组、缺血后处理组和联合处理组在造模前或/和造模后反复3次阻断开放左侧肺门。结果与结论:与缺血预处理组和缺血后处理组相比,联合处理组大鼠肺组织的干质量比、丙二醛和髓过氧化物酶降低(P<0.05),而肺组织中超氧化物歧化酶活性升高(P<0.05),肺组织病理损伤程度明显减轻;缺血预处理组与缺血后处理组大鼠肺组织超氧化物歧化酶活性、丙二醛水平及髓过氧化物酶活性接近(P>0.05),且肺组织病理损伤程度基本相似。而且缺血预处理与联合处理组中超氧化物歧化酶、丙二醛和髓过氧化物酶水平呈正相关。提示缺血预处理和缺血后处理联合应用对于减轻中性粒细胞的侵润和激活及氧化反应对于肺组织的损伤有明显的累积保护效应,从而可以更好的减轻肺缺血再灌注损伤程度。     

缺血预处理联合缺血后处理对肺移植中缺血再灌注肺损伤的影响

背景：研究显示缺血预处理和缺血后处理在缺血再灌注肺损伤中均具有明显的保护作用。目的：观察缺血预处理联合缺血后处理对肺移植中缺血再灌注损伤的累积保护效应。方法：将40只SD大鼠随机等分为假手术组、模型组、缺血预处理组、缺血后处理组和联合处理组。后4组建立缺血再灌注肺损伤动物模型,缺血预处理组、缺血后处理组和联合处理组在造模前或/和造模后反复3次阻断开放左侧肺门。结果与结论：与缺血预处理组和缺血后处理组相比,联合处理组大鼠肺组织的干质量比、丙二醛和髓过氧化物酶降低（P〈0.05）,而肺组织中超氧化物歧化酶活性升高（P〈0.05）,肺组织病理损伤程度明显减轻;缺血预处理组与缺血后处理组大鼠肺组织超氧化物歧化酶活性、丙二醛水平及髓过氧化物酶活性接近（P〉0.05）,且肺组织病理损伤程度基本相似。而且缺血预处理与联合处理组中超氧化物歧化酶、丙二醛和髓过氧化物酶水平呈正相关。提示缺血预处理和缺血后处理联合应用对于减轻中性粒细胞的侵润和激活及氧化反应对于肺组织的损伤有明显的累积保护效应,从而可以更好的减轻肺缺血再灌注损伤程度。     

Cyclic arginine-glycine-aspartate attenuates acute lung injury in mice after intestinal ischemia/reperfusion

Introduction

Intestinal ischemia is a critical problem resulting in multiple organ failure and high mortality of 60 to 80%. Acute lung injury (ALI) is a common complication after intestinal ischemia/reperfusion (I/R) injuries and contributes to the high mortality rate. Moreover, activated neutrophil infiltration into the lungs is known to play a significant role in the progression of ALI. Integrin-mediated interaction is involved in neutrophil transmigration. Synthetic peptides containing an arginine-glycine-aspartate sequence compete with adhesive proteins and inhibit integrin-mediated interaction and signaling. Thus, we hypothesized that the administration of a cyclic arginine-glycine-aspartate peptide (cRGD) inhibited neutrophil infiltration and provided protection against ALI induced by intestinal I/R.

Methods

Ischemia in adult male C57BL/6 mice was induced by fastening the superior mesenteric artery with 4-0 suture. Forty-five minutes later, the vascular suture was released to allow reperfusion. cRGD (5 mg/kg body weight) or normal saline (vehicle) was administered by intraperitoneal injection 1 hour prior to ischemia. Blood, gut, and lung tissues were collected 4 hours after reperfusion for various measurements.

Results

Intestinal I/R caused severe widespread injury to the gut and lungs. Treatment with cRGD improved the integrity of microscopic structures in the gut and lungs, as judged by histological examination. Intestinal I/R induced the expression of β₁, β₂ and β₃ integrins, intercellular adhesion molecule-1, and fibronectin. cRGD significantly inhibited myeloperoxidase activity in the gut and lungs, as well as neutrophils and macrophages infiltrating the lungs. cRGD reduced the levels of TNF-α and IL-6 in serum, in addition to IL-6 and macrophage inflammatory protein-2 in the gut and lungs. Furthermore, the number of TUNEL-staining cells and levels of cleaved caspase-3 in the lungs were significantly lowered in the cRGD-treated mice in comparison with the vehicle mice.

Conclusions

Treatment with cRGD effectively protected ALI and gut injury, lowered neutrophil infiltration, suppressed inflammation, and inhibited lung apoptosis after intestinal I/R. Thus, there is potential for developing cRGD as a treatment for patients suffering from ALI caused by intestinal I/R.     

麻醉方式对序贯式双肺移植患者呼吸功能及肺功能的影响

背景：在非体外循环的条件下,保证患者在麻醉效果良好的情况下完成序贯式双肺移植,胸段硬膜外复合全静脉麻醉和全静脉麻醉的选择上尚存在争议。 目的：观察序贯式双肺移植过程中两种不同的麻醉方式对患者呼吸功能及肺生物学功能的影响。 方法：将24例序贯式双肺移植患者分为全静脉麻醉组及硬膜外复合全静脉麻醉组。对两组患者麻醉后单、双肺通气10 min后的氧耗量、二氧化碳排出量、呼吸商和能量消耗进行测定。同时,对比分析两组患者移植过程中去甲肾上腺素、肾上腺素、皮质醇以及血糖水平参数变化。 结果与结论：两组患者在移植后6个月、1年及3年的随访调查中,肺功能均得到明显的改善,血气分析状况良好,两组差异无显著性意义。两组患者的并发症发生率、急性排斥反应及死亡率差异均无显著性意义（P〉0.05）。麻醉后硬膜外复合全静脉麻醉组单、双肺通气患者的氧耗量、二氧化碳排出量和能量消耗指标均明显高于全静脉麻醉组相同时段对应指标（P〈0.05）。同组患者单肺通气的氧耗量、二氧化碳排出量和呼吸商指标低于双肺通气,但差异不明显（P〉0.05）。硬膜外复合全静脉麻醉组单、双肺通气患者的去甲肾上腺素、肾上腺素、皮质醇以及血糖水平均明显低于全静脉麻醉组相同时段对应水平（P〈0.05）。全静脉麻醉组麻醉后双肺通气患者的皮质醇激素水平明显高于单肺通气患者（P〈0.05）。硬膜外复合全静脉麻醉组患者去甲肾上腺素、肾上腺素、皮质醇以及血糖水平在单、双肺通气时的差异不明显（P〉0.05）。提示在双肺移植过程中,胸段硬膜外复合全静脉麻醉与全静脉麻醉相比,患者氧耗量、二氧化碳排出量和能量代谢明显增强,可减轻应激反应,且麻醉后代谢、应激情况不受通气方式影响。     

1例双肺移植术后患者并发特发性高氨血症的护理

总结1例双肺移植术后并发特发性高氨血症患者的护理经验。护理要点：肺移植术后特发性高氨血症的早期预警;综合性降氨治疗的护理,包括间歇性血液透析联合连续性肾脏替代治疗的护理、药物降氨护理、动态化的营养支持护理;加强免疫抑制药物的特殊管理;实施移植肺功能的持续性个性化训练;开展认知功能训练。经过积极治疗,患者意识转清,血氨浓度恢复正常,顺利出院。     

肾移植缺血再灌注损伤与一氧化氮和一氧化氮合酶

目的:肾移植缺血再灌注损伤主要临床表现为移植肾功能延迟恢复,不仅增加急性排斥反应的风险,而且还是影响肾移植长期存活率的一个重要因素。探讨一氧化氮和一氧化氮合酶在肾移植缺血再灌注损伤中的变化规律及作用。方法:应用计算机检索Medline及中国期刊全文数据库1997-01/2006-10有关一氧化氮、一氧化氮合酶在肾移植缺血再灌注损伤中的变化规律及作用方面的文献,英文检索词"Kidney,ischemia-reperfusion injury,nitric oxide synthase,nitric oxide";中文检索词"肾脏,缺血再灌注,一氧化氮,一氧化氮合酶"。对资料进行初审,排除重复性研究及综述文献。共收集到符合上述要求的文献48篇,选择14篇进行分析。结果:肾脏缺血再灌注损伤中诱导型一氧化氮合酶和内皮型一氧化氮合酶比例失衡,表现为内皮型一氧化氮合酶相对降低和诱导型一氧化氮合酶相对增高。内皮型一氧化氮合酶来源的一氧化氮是肾脏缺血再灌注损伤中的保护因子,诱导型一氧化氮合酶来源的一氧化氮是肾脏缺血再灌注损伤中的损伤因子。结论:肾移植缺血再灌注损伤中诱导型一氧化氮合酶和内皮型一氧化氮合酶比例失衡,其变化规律为药物干预一氧化氮合酶从而减轻肾脏缺血再灌注损伤提供了依据。     

肢体缺血再灌注致肺损伤及丹参的保护作用

目的 通过动物实验方法观察丹参对肢体缺血再灌注所致肺损伤的保护作用。方法110只Wistar大鼠随机分成正常对照、缺血3h和缺血3h用丹参三个组。实验组于缺血、再灌注1、2、3和24h取材,光镜下对比观察和组织学评估。结果肢体缺血和再灌注后,实验组肺泡隔增厚、水肿,毛细血管扩张、充血,大量多核白细胞浸润、贴壁,部分肺不张。用丹参组的病理改变明显轻于未用丹参组。结论丹参能有效地减轻肢体缺血再灌注所致的肺损伤。     

PKCbeta regulates ischemia/reperfusion injury in the lung

Activation of PKCbetaII is associated with the response to ischemia/reperfusion (I/R), though its role, either pathogenic or protective, has not been determined. In a murine model of single-lung I/R, evidence linking PKCbeta to maladaptive responses is shown in the following studies. Homozygous PKCbeta-null mice and WT mice fed the PKCbeta inhibitor ruboxistaurin subjected to I/R displayed increased survival compared with controls. In PKCbeta-null mice, phosphorylation of extracellular signal-regulated protein kinase-1 and -2 (ERK1/2), JNK, and p38 MAPK was suppressed in I/R. Expression of the immediate early gene, early growth response-1 (Egr-1), and its downstream target genes was significantly increased in WT mice in I/R, particularly in mononuclear phagocytes (MPs), whereas this expression was attenuated in PKCbeta-null mice or WT mice fed ruboxistaurin. In vitro, hypoxia/reoxygenation-mediated induction of Egr-1 in MPs was suppressed by inhibition of PKCbeta, ERK1/2, and JNK, but not by inhibition of p38 MAPK. These findings elucidate key roles for PKCbetaII activation in I/R by coordinated activation of MAPKs (ERK1/2, JNK) and Egr-1.     

肺移植术后的气管支气管曲霉病

目前肺移植是终末期肺疾病的唯一选择。侵袭性曲霉病仍然是肺移植术后的重要并发症,早期诊断困难,抗真菌药物的毒性及与免疫抑制药物的相互作用,导致其病死率较高。最近越来越多的文献     

原位肝移植后的严重腹腔感染

背景：肝移植后严重腹腔感染是肝移植受者围手术期严重并发症,是导致患者死亡或者移植肝失功能的重要原因之一。目的：探讨原位肝移植后严重腹腔感染的发病原因及诊治经验。方法：回顾性分析2004年3月至2011年11月作者参与实施的186例原位肝移植患者发生严重腹腔感染的临床资料。结果与结论：186例患者中发生严重腹腔感染16例,其中5例胆管吻合口漏致肝下间隙大量积液并感染;10例肝移植手术创面广泛渗血致肝周大量积血并感染,1例移植后食道下段瘘致左侧膈下大量积液并感染。诊断明确3 d内再次手术12例,均无死亡;诊断明确3 d后再次手术4例,其中1例于肝移植后21 d、再次术后5d因多器官功能衰竭死亡。结果可见肝移植后严重腹腔感染是肝移植受者围手术期严重并发症之一,采取积极复苏、多脏器功能支持、控制性手术清除感染病灶以及充分引流等综合治疗措施是治疗肝移植后腹腔严重感染的关键。     

肝移植后急性肺损伤26例危险因素分析

通过回顾分析重庆医科大学附属第一医院肝胆外科于2007-08/2008-08完成的26例肝移植患者临床资料来探讨肝移植后早期急性肺损伤的相关危险因素.26例患者中,男22例、女4例;活体右半肝移植4例,尸肝移植22例.移植后18例出现急性肺损伤,1例尸体肝移植后7d死于多器官功能衰竭.18例急性肺损伤患者中,原发性肝癌2例,肝硬化失代偿13例,慢性重症肝炎3例;肝功能Child B级9例、Child C级9例;移植前凝血功能障碍8例;移植中出血/输血>6000mL 15例;无肝期/低血压时间>103min 6例;移植中新肝血流恢复后30min谷丙转氨酶>10 μkat/L 12例.从以上得出结论;肝硬化失代偿,慢性重症肝炎,移植前凝血功能障碍,移植中出血/输血>6 000 mL,移植中新肝血流恢复后30 min谷丙转氨酶>10 μkat/L均是肝移植后发生急性肺损伤的重要影响因素,应高度警惕急性肺损伤的发生.