糖皮质激素和免疫抑制剂治疗慢性肾小球疾病并发重症肺部感染

目的：探讨慢性肾小球疾病患者用糖皮质激素、免疫抑制剂后并发重症肺部感染的，临床特点及治疗。方法：对29例慢性肾小球疾病患者用糖皮质激素、免疫抑制剂后并发重症肺部感染的临床资料进行回顾分析。结果：29例患者中，男性25例，女性4例，年龄42．9±16．3（23～62）岁。感染发生于用药后3个月内者20例（69．0％），3～6个月者5例（17．2％），〉6个月者4例（13．8％），平均（4．47±5．16）个月。临床症状以发热起病最多，占86．2％；咳嗽51．0％，多为轻度干咳，痰少；起病时即有胸闷气促者9例（31．0％）；病情进展迅速，2～3d即可出现呼吸衰竭，需要呼吸机辅助呼吸。入院时胸部X线片多无严重改变，但进展快，而高分辨CT（HRCT）则在早期即可显示明显病变。随病情进展，所有患者的胸部X片和HRCT均显示双肺弥漫性病变。29例感染患者中仅10例（34．5％）检出病原体，共检出病原体18例次，其中7例次（38．9％）为细菌，6例次（33．3％）为真菌，5例次（27．8％）为病毒；所有患者明确感染后均停用免疫抑制剂或减量，给予积极抗感染治疗，并加强支持治疗，纠正水电解质酸碱平衡紊乱，予呼吸机辅助呼吸。16例感染控制，好转出院并门诊随访，13例死亡，病死率44．8％。结论：慢性肾小球疾病用糖皮质激素、免疫抑制剂并发的肺部感染多发生于用药后3个月内，早期联合抗细菌、抗病毒、抗真菌及抗支原体治疗，及时调整免疫治疗方案，加强支持治疗，适时予以呼吸机辅助呼吸是救治成功的关键。     

肾移植术后肺部感染的诊治

目的提高肾移植术后肺部感染的诊疗水平。方法回顾性分析总结36例肾移植术后并发肺部感染患者的临床资料及诊治情况。结果29例患者找到病原体47例次，7例未找到确切的病原体；并发急性肺损伤／急性呼吸窘迫综合征者共20例，其中12例行机械通气治疗，10例（83．3％）治愈；19例患者行纤维支气管镜（纤支镜）介入诊疗，其中16例（84．2％）明确了病原体，12例患者经纤支镜介入治疗后，临床症状均有不同程度改善；本组36例患者中，32例（88．9％）治愈，2例死亡，2例因经济原因放弃治疗自动出院。结论肾移植术后肺部感染患者应积极进行病原学的检测，重视影像学检查的意义；早期经验性治疗能否覆盖可能感染的病原体是治疗能否成功的关键；纤支镜介入诊疗对于提高肾移植术后肺部感染（尤其是莺症肺部感染）的治愈率有重要作用。     

免疫抑制剂在肾移植术后肺部感染中的应用

目的:肾移植术后肺部感染治疗难度较大,如何有效的保护或者替代移植肾功能,又不能使患者的机体免疫状态极度低下,免疫抑制剂的调整使用至关重要.文章旨在探讨肾移植术后肺部感染患者免疫抑制剂的应用方案.方法:选择解放军空军总医院2002-01/2006-12收治的同种异体肾移植术后肺部感染患者20例,其中重症肺部感染13例.症状较轻的患者,给予免疫抑制剂调整及减量、抗感染等综合治疗;重症肺部感染立即停用所有免疫抑制剂,给予抗感染治疗,并根据肺部感染治疗效果,逐渐加用常规免疫抑制剂.观察20例肾移植术后肺部感染病例的治疗转归.结果:7例症状较轻的患者全部治愈.13例重症肺部感染患者中治愈9例,死亡2例,放弃治疗2例,治愈的9例中仅有1例发生移植肾急性排斥反应1次,经抗胸腺细胞球蛋白治疗逆转.治愈病例移植肾功能正常.结论:早期诊断、及时治疗并调整免疫抑制剂方案有利于提高肾移植术后肺部感染的治愈率.     

肾移植受者巨细胞病毒感染及免疫抑制剂的影响

目的探讨肾移植受者巨细胞病毒（CMV）感染率及免疫抑制剂对其的影响。方法214例肾移植受者术后静滴甲基泼尼松龙（Mp）、抗淋巴细胞球蛋白（ALG）作为诱导期免疫抑制治疗；基础免疫抑制剂治疗为环孢素A、泼尼松和硫唑嘌呤；急性排斥反应时静滴Mp治疗，无效时给予ALG或OKT3。采用免疫细胞化学法测定外周血白细胞CMV抗原，术后头3个月每周1次。结果214例肾移植受者中，126例（61.7％）术后发生CMV感染；70例（32．7％）发生急性排斥反应，其中52例（74．3％）发生CMV感染，明显高于无急性排斥反应患者的51．4％（P〈0．01）。在126例CMV感染和88例无CMV感染的肾移植受者中，诱导期免疫抑制剂ALG平均剂量分别为（14．1±1.3）支和（13．2±0．9）支（P〉0.05），平均疗程分别为（4．7±1．3）d和（4．4±0．9）d（P〉0．05），急性排斥反应发生率分别为42．3％和20．5％（P〈0．01），其中需使用ALG治疗例数分别为23例、6例（P〈0．05），需OKT3治疗例数为15例和1例（P〈0．05）。结论肾移植受者术后CMV感染率高；术后短期的ALG诱导治疗可能不增加CMV感染发生率；急性排斥反应后免疫抑制剂尤其是ALG或OKT3的使用与CMV感染密切相关。     

肾移植术后并发重症肺部感染的原因与护理

目的探讨肾移植术后并发重症肺部感染的原因与护理。方法回顾性分析29例肾移植术后并发重症肺部感染患者的临床资料。结果29例重症肺部感染患者中17例（58．6％）救治成功，12例（41．4％）因合并急性呼吸窘迫综合征抢救无效死亡。结论重症肺部感染是肾移植受者术后近期死亡的主要原因之一；果断减少或停用免疫抑制剂、早期联合用药抗感染治疗、制定个体化护理措施、积极配合医师的诊断与治疗等对患者的成功救治至关重要。     

肾移植后肺部感染治疗中免疫抑制剂的应用

背景:肾移植后肺部感染病情进展快,重症肺炎死亡率高,对其进行早期诊断及治疗具有重要意义,但部分患者因免疫抑制剂的调整,出现移植肾功能受损。目的:探讨肾移植后肺部感染治疗过程中免疫抑制剂的应用方案。方法:回顾分析85例肺部感染的肾移植患者的临床资料。肺部感染发生于肾移植后1-6个月43例(其中2-4个月39例),6-12个月7例,12-24个月7例,24-36个月6例,大于36个月22例。根据患者病情,予以调整免疫抑制剂,联合应用小剂量激素抗炎保护移植肾功能,针对病原学抗感染,呼吸衰竭者给予呼吸机辅助呼吸,同时予以降温及营养支持等对症治疗。肺部感染早期减少或停用免疫抑制44例,进展期减少或调整免疫制剂19例,重症肺炎期停用免疫抑制剂5例,肺炎早期及进展期逐步调整免疫抑制15例,肺炎早期减量至重症肺炎停用免疫抑制剂2例。减少或停用免疫抑制剂3-51 d,平均10.7 d。结果与结论:85例患者中治愈81例,死亡4例。4例死亡病例中,2例死于急性呼吸衰竭,2例死于多器官功能衰竭。治愈的81例中出现急性排异反应3例,移植肾功能受损6例。结果提示,肾移植后肺部感染短时间减少或停用免疫抑制剂,有利于提高治愈率,减少死亡率,及时恢复免疫制剂的应用,能有效保护移植肾功能,尤其是移植肾功能不全患者,肺部炎症进展控制住,及时恢复免疫抑制,在保护移植肾功能的意义更大。     

霉酚酸酯等新三联在肾移植术后的近期疗效

目的：观察霉酚酸酯（MMF）在预防肾移植术后急性排斥及肺部感染的情况。方法：89例肾移植后应用皮质激素（Perd），环孢素（CsA），MMF（或）硫唑嘌呤（Aza）三联免疫抑制剂治疗，其中分成MMF组52例，Aza组37例，MMF组中适当减少CsA用量。结果：临床观察3个月中，急性排斥（AR）发生率MMF组7．7％（4／52），Aza组16．2％（6／37），肺部感染率MMF组13．5％（7／52），Aza组21．6％（8／37），两者之间存在明显差异（P＜0．05）。结论：MMF组方案对减少AR发生率与并发肺部感染率有一定作用。     

外周血CD4^＋CD25^high调节性T细胞比例变化在肾移植受者移植后免疫监测中的应用

背景：相关实验表明调节性T细胞在移植物免疫耐受中起重要作用。 目的：观察外周血CD4^＋CD25^high调节性T细胞比例变化与肾移植受者移植后免疫变化的相关性。 设计、时间及地点：回顾性病例分析,于2007-09／2008-07在广东省第二人民医院器官移植中心及其实验室完成。 参试者：52例病情稳定的维持性血液透析患者行同种异体肾移植治疗。 方法：肾移植后患者均服用三联免疫抑制剂。所有患者移植后发生急性移植肾排斥反应以及感染均按照相应指南诊断及治疗。分别于移植前和移植后1,2,4,8,12周以及发生排斥反应和感染时抽血检测外周血CD4^＋CD25^＋调节性T细胞。按其免疫力恢复情况分为正常组26例,排斥反应组17例,感染组9例。 主要观察指标：用流式细胞仪检测外周血CD4^＋CD25^high调节性T细胞的比例,所得结果进行相关分析。 结果：与正常组比较：排斥反应组CD4^＋CD25^highFoxP3／CD4^＋的比值降低（P〈0．05）,而感染组显著增高（P〈0．01）。与感染组比较：排斥反应组CD4^＋CD25^highFoxP3／CD4^＋的比值显著降低（P〈0．01）。 结论：肾移植后受者外周血CD4^＋CD25^high调节性T细胞比例与受者免疫状态密切相关。CD4^＋CD25^high调节性T细胞比例的变化可以反应机体的免疫状态的变化,其升高或降低可以作为预测肾移植受者移植后发生感染或排斥反应的指标之一。     

肾移植术后并发重症肺部感染的护理

目的:探讨肾移植术后并发重症肺部感染的护理方法。方法:回顾分析8例肾移植术后并发重症肺部感染患者的临床资料,总结有效的护理措施。结果:8例患者中6例救治成功,2例合并急性呼吸窘迫综合征,其中1例抢救无效死亡,1例放弃治疗出院。结论:重症肺部感染是肾移植术后死亡主要原因之一,早期有效抗感染治疗、果断减量或停用免疫抑制剂、加强营养支持、重视消毒隔工作等对于患者的预后至关重要。     

预致敏受者尸体肾移植术后的急性排斥反应

目的：预致敏肾移植受者的增加已是目前肾移植成功的重大影响因素。观察人类白细胞抗原氨基酸残基配型及新型免疫抑制剂治疗方案对预致敏患者肾移植术后急性排斥反应的治疗效应，寻找提高移植物存活率的最佳方案。方法：选择2003—01／2005—08在首都医科大学附属北京友谊医院行肾移植手术的患者396例，患者均知情同意。分组：①预致敏组（n=32）：即术前致敏患者。采用诱导治疗（抗淋巴细胞球蛋白100mg／d，3～7d）＋三联免疫抑制剂维持治疗方案（他克莫司＋霉酚酸酯＋激素）。②对照组（n=364）：未致敏患者。采用三联免疫抑制剂维持用药方案。比较两组患者肾移植术后6个月内急性排斥反应发生率、移植肾功能延迟恢复发生率及移植肾，患者1年存活率，同时分析人类白细胞抗原氨基酸残基配型对移植肾急性排斥反应的影响。结果：396例患者全部进入结果分析。①两组患者肾移植术后急性排斥反应发生率差异无显著性意义（P〉0．05）。预致敏组患者移植肾功能延迟恢复发生率显著高于对照组（P〈0．01）。②两组患者1年存活率差异无显著性意义（P〉0．05）。预致敏组患者1年移植肾存活率低于对照组（P〈0．05），如果去除患者死亡因素的影响，两组患者1年移植肾存活率差异无显著性意义（P〉0．05）。③预致敏组患者人类白细胞抗原氨基酸残基相配率高于对照组（P〈0．05）。预致敏组中氨基酸残基配型3-4错配患者的急性排斥反应发生率显著高于0-2错配患者（P〈0．01），高度致敏患者（移植术前群体反应抗体〉50％）急性排斥反应发生率显著高于低度致敏患者（群体反应抗体10％-20％）（P〈0．01）。结论：供受者之间良好的人类白细胞抗原氨基酸残基分型及采用新型免疫抑制药物治疗方案，对预防及减轻致敏患者移植术后急性排斥反应疗效确切，并可以缩短致敏患者等待移植手术的时间。     

银杏叶提取物对人工衰老大鼠肺肾功能的保护作用

背景衰老大鼠静脉注射脂多糖后能导致肺损伤,进而发现随着肺损伤的进展,影响肾功能.银杏叶提取物具有一定的清除自由基、改善血液流变学和保护血管内皮细胞等功能. 目的研究人工衰老大鼠肺损伤后是否发生肾功能不全,以验证老年多器官功能不全的肺启动机制,并观察银杏叶提取物对其是否有保护作用. 设计以实验动物为观察对象的随机对照的实验. 单位中国协和医科大学基础医学研究所病理生理学系. 材料实验于2001-05/2003-01在中国协和医科大学基础医学研究所病理生理学系实验室完成.选用36只Wistar雄性大鼠. 方法给大鼠每天1次经腹腔注入D-半乳糖(50 mg/kg),连续6周,复制衰老动物模型,再随机分为3组对照组(静脉注射生理盐水);脂多糖组(静脉注射脂多糖,5 mg/kg);银杏叶提取物+脂多糖组(注射脂多糖前7 d开始,每天银杏叶提取物灌胃1次,31 mg/kg).各组大鼠在给生理盐水或脂多糖后2 h或6 h取血和肺、肾组织. 主要观察指标用比色法测定血中肌酐、尿素氮含量;血、肺、肾组织中丙二醛、No2-/NO3-含量及谷胱甘肽过氧化物酶及Na+-K+-ATP酶活性的测定. 结果衰老大鼠在注射脂多糖后2,6h时已形成急性肺损伤.注射脂多糖 后2 h血中肌酐及尿素氮含量无明显升高,而6 h时均显著升高,分别为 (94.7±10.3)μmol/L,(11.4±1.9)mmol/L.在注射脂多糖后2h,血和肺组织 中丙二醛[(22.5+2.6)nmol/L,(25.8±2.9)μmol/gl和No2-/NO3-含量[(58.5 ±6.8)mmol/L,(34.6±3.8μmol/g]均显著升高,而谷胱甘肽过氧化物酶 [(355.1±45.0)μkat/g]及Na+-K+-ATP酶[(886.3±97.1)nkat/g]下降.上述指标 的变化持续至观察的6 h.而肾组织中上述指标仅在注射脂多糖后6 h才 有显著性变化.银杏叶提取物可显著缓解上述指标的变化. 结论脂多糖所致衰老大鼠的肺损伤可进一步诱导肾功能受损.银杏叶 提取物对脂多糖诱发的衰老大鼠的急性肺损伤和由此诱导的肾功能受 损有明显的保护作用.     

Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R,VEGF and VEGF-R2 modulation

Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis.Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP + EPO (3000 IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18 h post-surgery.Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2.Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality.This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLP-induced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair.     

Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil. An epidemiological study using the American-European Consensus Criteria

OBJECTIVES: To determine: (1) the frequency of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); (2) the mortality associated with these syndromes and (3) the influence of risk factors, comorbidities and organ system dysfunction in the mortality of ALI patients. DESIGN: Prospective cohort study. SETTING: Intensive care unit (ICU) of a general university hospital in Brazil. PATIENTS AND PARTICIPANTS: All patients that remained in the ICU for more than 24 h were evaluated regarding the presence/development of ALI/ARDS according to the 1994 American-European Consensus Conference. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: One thousand three hundred and one patients were studied and analyzed regarding mortality, risk factors, comorbidities and organ system dysfunction(s). The frequency of ALI was 3.8% (50), of which ARDS was 2.3% (30) and ALI/non-ARDS 1.5% (20) (p=0.15). The ICU mortality of patients with ALI was 44.0%; in ALI/non-ARDS and ARDS patients it was 40.0% and 46.7%, respectively (p=0.43). The hospital mortality of ALI patients was 48.0%; in ALI/non-ARDS and ARDS patients it was 50.0% and 46.7%, respectively (p=0.21). A multivariate analysis demonstrated that renal (ICU and hospital: p=0.002) and hematological dysfunction (ICU: p=0.008; hospital: p=0.02) were independently associated with ICU and hospital mortality in ALI patients. CONCLUSIONS: (1) The frequency of ALI was 3.8%, of which the frequency of ARDS was 2.3% and of ALI/non-ARDS 1.5%; (2) The ICU and hospital mortality of ALI patients was 44.0% and 48.0%, respectively; mortality rates of ARDS and ALI/non-ARDS did not differ significantly; (3) Renal and hematological dysfunction were associated with mortality in ALI patients.     

Direct effects of protein S in ameliorating acute lung injury

Summary. Objective: Protein S may exert an anticoagulant activity by enhancing the anticoagulant activity of activated protein C and/or by directly inhibiting the prothrombinase complex. Protein S itself may also directly regulate inflammatory responses and apoptosis. The role of protein S in acute lung injury (ALI) was unknown. This study evaluated the effect of protein S on ALI in the mouse. Methods: Animal ALI was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide (LPS). Mice were treated with protein S or saline by intraperitoneal injection 1 h before LPS instillation. Results: Activated protein or protein S alone and combined activated protein C + protein S therapy decreased inflammatory markers and cytokines in mice with acute lung injury. In LPS‐treated mice compared with controls ALI was induced as shown by significantly increased levels of total protein, tumor necrosis factor‐α, interleukin‐6 and monocyte chemoattractant protein‐1 in the bronchoalveolar lavage fluid. Mice with ALI treated with protein S had significantly decreased concentrations of tumor necrosis factor‐α and interleukin‐6 in the lung compared with untreated animals. Thrombin‐antithrombin III, a marker of the activity of the coagulation cascade, was unchanged. Protein S inhibited the expression of cytokines in vitro and increased activation of the Axl tyrosine kinase pathway in A549 epithelial cells. Conclusion: Protein S protects against LPS‐induced ALI, possibly by directly inhibiting the local expression of inflammatory cytokines without affecting coagulation.     

维生素D对脂多糖致急性肺损伤大鼠肺组织血管紧张素转化酶2和维生素D受体表达水平的影响

目的 观察维生素D(vitamin D,Vit D)对脂多糖(lipopolysaccharide,LPS)致Wistar大鼠急性肺损伤(acute lung injury,ALI)肺组织中血管紧张素转化酶2(angiotensinconverting enzyme 2,ACE2)和维生素D受体(vitamin D receptor,VDR)表达水平的影响.方法 采用尾静脉注射LPS方法制备大鼠ALI模型;将30只健康雄性Wistar大鼠随机(随机数字法)分为6组:正常对照组(NC组)、LPS组:尾静脉注射LPS 5mg/kg、Vit D组:给予Vit D活性形式(骨化三醇)25 μg/kg连续灌胃3d和(LPS+ Vit D) 1-3组:分别于骨化三醇1μg/kg、5μg/kg、25 μg/kg灌胃3d后尾静脉注射LPS 5mg/kg,所有大鼠于注射LPS的24 h后进行后续实验.分别观察大鼠一般情况,肺组织病理及肺干/湿重比变化、肺组织中VDR、ACE2蛋白及基因水平的表达.结果 LPS组大鼠病态表现(呼吸浅快、精神萎靡、口鼻可见血性分泌物)明显,(LPS+ VitD) 1-3组病态表现和肺组织病理损伤均较LPS组明显减轻.LPS组VDR和ACE2蛋白及基因水平的表达均较NC组和Vit D组显著降低(P＜0.05),(LPS+ VitD) 1-3组各组VDR和ACE2蛋白及基因水平的表达均较LPS组有所升高(P＜0.05),但仍显著低于Vit D组(P＜0.05),其中(LPS+ Vit D) 1-3组各组VDR蛋白及基因水平的表达差异无统计学意义(P＞0.05),ACE2的表达差异有统计学意义(P＜0.05).结论 Vit D能使LPS致ALI大鼠肺组织中ACE2和VDR蛋白及基因表达水平增加,故此推测ACE2和VDR表达增加可能对ALI的发生、发展起保护作用.     

毒性气体致急性肺损伤8例临床分析

目的：提高对毒性气体（ＰＧ）在短时间内大量吸入导致急性肺损伤（ＡＬＩ）的认识。方法：对１例二氧化氮吸入,１例二氧化氮和少量汞蒸气吸入,６例氯气吸入致ＡＬＩ的病例进行回顾性分析。主要观察ＰＧ吸入和ＡＬＩ的潜伏期、临床表现、胸片、动态血气分析、氧合指数（ＰａＯ２／ＦｉＯ２）、治疗方法和反应。结果：６例病人在吸入ＰＧ数分钟后出现呛咳、恶心、呕吐、停止吸入后好转,随后所有患者均继续吸入ＰＧ１～２ｈ,４～６ｈ后出现ＡＬＩ的表现,其中２例符合ＡＲＤＳ,经氧疗、短期大量使用糖皮质激素、抗生素、利尿等治疗。２例给予经面罩机械辅助通气治疗,皆痊愈。结论：提高ＰＧ吸入致ＡＬＩ的警惕。应加强防护,及时离开现场。     

大黄对家兔内毒素性急性肺损伤的保护作用研究

目的:观察大黄对家兔内毒素性急性肺损伤(ALI)的保护作用。方法:12只雄性新西兰兔待氧合指数(PaO2/FiO2)≤300mmHg(1mmHg=0.133kPa)时,将动物随机分为两组,每组6只。生理盐水对照组注入等量生理盐水;大黄组胃内注入大黄20g/kg。观察基础值,ALI时以及ALI后1、2、3、4、5和6h各时间点两组胃肠黏膜内pH值(pHi)、PaO2/FiO2、肺动态顺应性(Cdyn),测定ALI的生物学指标超氧化物歧化酶(SOD)活性,以及支气管肺泡灌洗液(BALF)中蛋白的含量。实验结束后,开胸取肺行组织学检查。结果:生理盐水对照组pHi在ALI后4、5和6h均较基础值时降低(P均<0.05),在ALI后5h和6h较ALI时降低(P均<0.05);大黄组pHi在ALI后4h和5h较生理盐水对照组升高(P均<0.05),而在6h较生理盐水对照组同时间点显著升高(P<0.01)。两组PaO2/FiO2在ALI后均有不同程度下降,且两组PaO2/FiO2在ALI后5h和6h差异有显著性(P<0.05和P<0.01)。两组Cdyn在ALI后均有不同程度的下降,但大黄组下降幅度较小,且两组Cdyn在ALI后5h和6h差异有显著性(P均<0.05)。两组SOD活性大黄组显著高于生理盐水对照组(P<0.01)。大黄组BALF中蛋白含量低于生理盐水对照组(P<0.05)。肺组织切片显示大黄组肺组织损伤明显较生理盐水对照组轻。结论:胃内注入大黄对兔内毒素性ALI有保护作用。     

Effects of combined high-dose partial liquid ventilation and almitrine on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury

OBJECTIVES: To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN AND SETTING: Prospective, controlled animal study in an animal research facility of a university hospital. INTERVENTIONS: ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6). MEASUREMENT AND RESULTS: Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone. CONCLUSIONS: In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics.     

Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury

OBJECTIVES: To study the effects of an inhaled endothelin A (ET(A)) receptor antagonist on hemodynamics and pulmonary gas exchange in experimental acute lung injury (ALI). DESIGN AND SETTING: Prospective, randomized, and controlled study in a university laboratory. PARTICIPANTS AND INTERVENTIONS: Sixteen pigs were ventilated in a volume controlled mode during general anesthesia. ALI was induced by surfactant depletion using repetitive lung lavages until the PaO2/FIO2 ratio was below 100 mmHg. The animals were then randomly assigned to receive either a nebulized ET(A) receptor antagonist (LU-135252, 3 mg/kg, inhaled over 1 h; LU group) or nebulization of saline (5-10 ml inhaled over 1 h) with no further intervention (controls). MEASUREMENTS AND RESULTS: Parameters of hemodynamics and gas exchange were measured for 6 h after induction of ALI. In the LU group intrapulmonary right-left shunting (QS/QT) decreased from 58 +/- 8% at the onset of ALI to 27 +/- 12% 3 h and 24 +/- 9% 6 h after ALI (p < 0.05); PaO2 increased from 55 +/- 12 to 257 +/- 148 mmHg 3 h and 270 +/- 136 mmHg 6 h after ALI. (p < 0.05), whereas in controls QS/QT and PaO2 did not improve over the 6 h after onset of ALI. In the LU group mean pulmonary artery pressure was stable for 6 h after ALI (26-29 mmHg), while in controls it increased from 28 +/- 2 to 41 +/- 2 mmHg (p < 0.05). Inhaled LU-135252 reduced cardiac output by 31 +/- 11% (p < 0.05) and increased systemic vascular resistance by 60 +/- 29 % (p < 0.05), while these parameters remained stable in controls. CONCLUSION: In this porcine model of ALI the inhalation of an ET(A) receptor antagonist improved arterial oxygenation and maintained a stable pulmonary artery pressure without inducing systemic vasodilatation.