Plasma and lipids from stored platelets cause acute lung injury in an animal model

BACKGROUND: Transfusion of PLT concentrates may cause TRALI, a life-threatening reaction that has been linked to the infusion of anti-WBC immunoglobulins or older, stored PLTs that contain bioactive lipids. We hypothesize that lipids generated during storage of PLTs cause TRALI in a two-event animal model. STUDY DESIGN AND METHODS: Plasma from both whole-blood PLTs (WB-PLTs) and apheresis PLTs (A-PLTs) was isolated on Day 0 (D.0) and Day 5 (D.5) of storage and heat-treated before use. Rats were pretreated with saline or 2 mg per kg endotoxin (LPS), anesthetized, and the lungs were ventilated, isolated, and perfused with saline or 5-percent PLT plasma. Pulmonary artery pressure, pulmonary edema, and leukotriene B4 levels (perfusate) were measured. RESULTS: Plasma from D.5, but not D.0, of the identical WB-PLT and A-PLT units caused injury in lungs from LPS-pretreated rats (LPS/D.5) evidenced by increases in pulmonary edema and leukotriene B4 (p < 0.05). Lipid extracts and purified lipids from D.5 PLT plasma also elicited injury in lungs from LPS-pretreated rats (p < 0.05). Saline/D.5 plasma or lipids or LPS/D.0 did not cause pulmonary edema. Prestorage WBC reduction was ineffective in inhibiting TRALI. CONCLUSION: PLT-induced TRALI may be the result of two events: 1) the clinical condition of the patient and 2) the infusion of lipids in stored PLTs.     

Identification of lipids that accumulate during the routine storage of prestorage leukoreduced red blood cells and cause acute lung injury

BACKGROUND: Lipids accumulate during the storage of red blood cells (RBCs), prime neutrophils (PMNs), and have been implicated in transfusion‐related acute lung injury (TRALI). These lipids are composed of two classes: nonpolar lipids and lysophosphatidylcholines based on their retention time on separation by high‐pressure liquid chromatography. Prestorage leukoreduction significantly decreases white blood cell and platelet contamination of RBCs; therefore, it is hypothesized that prestorage leukoreduction changes the classes of lipids that accumulate during storage, and these lipids prime PMNs and induce acute lung injury (ALI) as the second event in a two‐event in vivo model. STUDY DESIGN AND METHODS: RBC units were divided: 50% was leukoreduced (LR‐RBCs), stored, and sampled on Day 1 and at the end of storage, Day 42. Priming activity was evaluated on isolated PMNs, and the purified lipids from Day 1 or Day 42 were used as the second event in the in vivo model. RESULTS: The plasma and lipids from RBCs and LR‐RBCs primed PMNs, and the LR‐RBC activity decreased with longer storage. Unlike RBCs, nonpolar lipids comprised the PMN‐priming activity from stored LR‐RBCs. Mass spectroscopy identified these lipids as arachidonic acid and 5‐, 12‐, and 15‐hydroxyeicsotetranoic acid. At concentrations from Day 42, but not Day 1, three of four of these lipids individually, and the mixture, primed PMNs. The mixture also caused ALI as the second event in a two‐event model of TRALI. CONCLUSION: We conclude that the nonpolar lipids that accumulate during LR‐RBC storage may represent the agents responsible for antibody‐negative TRALI.     

Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary vasoconstriction: evidence against a role for platelet-activating factor.

1. The role of platelet-activating factor in the attenuated hypoxic pulmonary vasoconstriction associated with lung injury was evaluated using specific platelet-activating factor antagonists and an isolated perfused lung preparation. 2. Intratracheal bleomycin was administered to rats to produce acute lung injury. Animals received intratracheal saline (control), intratracheal bleomycin or the platelet-activating factor antagonists BN 52021, WEB 2170 or WEB 2086 before and after bleomycin treatment. Forty-eight hours after intratracheal administration of bleomycin or saline the animals were killed. 3. The increases in pulmonary artery pressure during two periods of hypoxic ventilation and in response to 0.2 microgram of angiotensin II were measured. Acetylcholine-induced vasodilatation after pre-constriction with prostaglandin F2 alpha was also measured. To quantify lung injury, the wet/dry ratio of lung weight was determined. 4. Bleomycin treatment attenuated the first and second hypoxic pressor responses by 93% and 77%, respectively, but not the pressor response to angiotensin II nor the vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the first hypoxic pressor response compared with bleomycin treatment alone, but the structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB 2086 had no significant effect on the bleomycin-induced attenuation of hypoxic pulmonary vasoconstriction. None of the platelet-activating factor antagonists blocked the increase in the wet/dry lung weight ratio induced by bleomycin. 5. Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary vasoconstriction, an effect that does not appear to be mediated by platelet-activating factor. The mechanism remains to be elucidated, but may involve destruction of the hypoxic 'sensor' within the respiratory tract.     

Age of blood and recipient factors determine the severity of transfusion-related acute lung injury (TRALI)

Introduction

Critical care patients frequently receive blood transfusions. Some reports show an association between aged or stored blood and increased morbidity and mortality, including the development of transfusion-related acute lung injury (TRALI). However, the existence of conflicting data endorses the need for research to either reject this association, or to confirm it and elucidate the underlying mechanisms.

Methods

Twenty-eight sheep were randomised into two groups, receiving saline or lipopolysaccharide (LPS). Sheep were further randomised to also receive transfusion of pooled and heat-inactivated supernatant from fresh (Day 1) or stored (Day 42) non-leucoreduced human packed red blood cells (PRBC) or an infusion of saline. TRALI was defined by hypoxaemia during or within two hours of transfusion and histological evidence of pulmonary oedema. Regression modelling compared physiology between groups, and to a previous study, using stored platelet concentrates (PLT). Samples of the transfused blood products also underwent cytokine array and biochemical analyses, and their neutrophil priming ability was measured in vitro.

Results

TRALI did not develop in sheep that first received saline-infusion. In contrast, 80% of sheep that first received LPS-infusion developed TRALI following transfusion with "stored PRBC." The decreased mean arterial pressure and cardiac output as well as increased central venous pressure and body temperature were more severe for TRALI induced by "stored PRBC" than by "stored PLT." Storage-related accumulation of several factors was demonstrated in both "stored PRBC" and "stored PLT", and was associated with increased in vitro neutrophil priming. Concentrations of several factors were higher in the "stored PRBC" than in the "stored PLT," however, there was no difference to neutrophil priming in vitro.

Conclusions

In this in vivo ovine model, both recipient and blood product factors contributed to the development of TRALI. Sick (LPS infused) sheep rather than healthy (saline infused) sheep predominantly developed TRALI when transfused with supernatant from stored but not fresh PRBC. "Stored PRBC" induced a more severe injury than "stored PLT" and had a different storage lesion profile, suggesting that these outcomes may be associated with storage lesion factors unique to each blood product type. Therefore, the transfusion of fresh rather than stored PRBC may minimise the risk of TRALI.     

Pulmonary pathology of rapidly fatal transfusion-related acute lung injury reveals minimal evidence of diffuse alveolar damage or alveolar granulocyte infiltration

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐associated death in the United States. Its diagnosis is based on clinical and radiographic changes that are indistinguishable from acute lung injury/acute respiratory distress syndrome (ALI/ARDS). TRALI is presumed to be a form of ALI/ARDS; however, it differs in its triggering events and associated mortality. Two cases of rapidly fatal TRALI in which the postmortem pathology differed from that classically associated with ALI/ARDS are reported. CASE REPORT: Two men (aged 75 and 83 years) developed rapidly fatal TRALI after receiving single units of plasma for correction of elevated international normalized ratios. The donors were found to have white blood cell (WBC) antibodies that included specificities for WBC antigens expressed by the recipient (HLA Class I or Class II and/or HNA‐3b [5a] antibody). Autopsy findings in both patients revealed bilateral pleural effusions and extensive patchy areas of alveoli filled with proteinaceous fluid. The pulmonary capillaries were congested with red blood cells and WBCs. Diffuse alveolar damage, including interstitial inflammation, intraalveolar granulocyte infiltration, and hyaline membrane formation, were not identified in either case. CONCLUSION: In both patients the clinical and radiographic findings were indicative of TRALI and indistinguishable from ALI/ARDS. However, diffuse alveolar damage, the classic autopsy finding in ARDS, was not identified, suggesting a different pathogenesis. Further studies are needed on the role of polymorphonuclear cells in the initiating events of TRALI that lead to ALI and the resulting breakdown of the permeability integrity of the alveolar walls.     

Ultraviolet B light-exposed human platelets mediate acute lung injury in a two-event mouse model of transfusion

BACKGROUND: Ultraviolet B (UVB) light has been used alone on platelet (PLT) transfusion products to prevent alloimmunization or with chemical sensitizers to reduce pathogens. Such processing can damage PLTs and potentiate their storage lesion. Transfusion‐related acute lung injury (ALI) has occurred in patients whose underlying condition led to an inflamed endothelium and who were transfused with products that contained either HLA or HNA antibodies or biologic modifiers such as lipids or antigens from stored cells. Clinical trials of UV‐treated PLTs in patients with thrombocytopenia generated controversy regarding association of these cells with respiratory distress. We evaluated whether UVB PLTs could mediate ALI in an animal model of ALI. STUDY DESIGN AND METHODS: We used a two‐event animal model where the sensitizing event was lipopolysaccharide (LPS) and the second event was infusion of human PLTs or UVB human PLTs (2.4 J/cm²). Infused human PLTs were followed with whole animal imaging, lung histology, confocal microscopy, lung water, and changes in bronchoalveolar lavage fluid (BALF) related to ALI. RESULTS: In LPS‐treated mice UVB human PLTs accumulated in the lungs and were associated with ALI manifested by increased protein and white blood cells (WBCs) in BALF. Untreated human PLTs did not accumulate in the lungs or increase BALF protein or WBC counts. CONCLUSIONS: We provide a proof of principle that UVB human PLTs can accumulate in lungs of LPS‐primed animals and mediate ALI. PLTs exposed to high doses of UVB could potentially mediate similar effects in patients predisposed with sepsis or other causes of endothelial cell inflammation.     

Effects of initial passage of endotoxin through the liver on the extent of acute lung injury in a rat model

We hypothesized that the extent of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is modified with its initial passage through the liver. We tested this hypothesis by administering LPS, 5 mg/kg, or saline to 120 male Wistar rats via the portal vein (PV) or the inferior vena cava (IVC) over 1 h. Four experimental groups of rats were administered saline into the PV, saline into the IVC, LPS into the PV (LPS-PV group), and LPS into the IVC (LPS-IVC group), respectively. At 15 and 30 min after onset of 51Chromium-LPS infusion, the gamma counts in the liver were higher in the LPS-PV group than that in the LPS-IVC group. The ratio of 125Iodine-albumin counts in lung tissue to that in plasma per unit of weight (as an assessment of pulmonary microvascular permeability) at 240 min after onset of LPS stimulation, the accumulation of polymorphonuclear cell (assessed by myeloperoxidase activity) and the concentration of tumor necrosis factor alpha in the lung at 60 and 240 min after onset of LPS infusion, were higher in the LPS-IVC group than in the LPS-PV group. Significant differences in several factors indicative of inflammation and in the extent of LPS-induced ALI were observed after the onset of LPS infusion, depending on whether it was delivered via the PV or the IVC. These observations suggest that the entrapping of LPS during its initial passage through the hepatic circulation may attenuate LPS-induced ALI within 4 h of initiation of LPS stimulation.     

Primed stimulation of isolated perfused rabbit lung by endotoxin and platelet activating factor induces enhanced production of thromboxane and lung injury.

Bacterial sepsis often precedes the development of the adult respiratory distress syndrome (ARDS) and bacterial endotoxin (LPS) produces a syndrome similar to ARDS when infused into experimental animals. We determined in isolated, buffer-perfused rabbit lungs, free of plasma and circulating blood cells that LPS synergized with platelet activating factor (PAF) to injure the lung. In lungs perfused for 2 h with LPS-free buffer (less than 100 pg/ml), stimulation with 1, 10, or 100 nM PAF produced transient pulmonary hypertension and minimal edema. Lungs perfused for 2 h with buffer containing 100 ng/ml of Escherichia coli 0111:B4 LPS had slight elevation of pulmonary artery pressure (PAP) and did not develop edema. In contrast, lungs exposed to 100 ng/ml of LPS for 2 h had marked increases in PAP and developed significant edema when stimulated with PAF. LPS treatment increased capillary filtration coefficient, suggesting that capillary leak contributed to pulmonary edema. LPS-primed, PAF-stimulated lungs had enhanced production of thromboxane B2 (TXB) and 6-keto-prostaglandin F1 alpha (6KPF). Indomethacin completely inhibited PAF-stimulated production of TXB and 6KPF in control and LPS-primed preparations, did not inhibit the rise in PAP produced by PAF in control lungs, but blocked the exaggerated rise in PAP and edema seen in LPS-primed, PAF-stimulated lungs. The thromboxane synthetase inhibitor dazoxiben, and the thromboxane receptor antagonist, SQ 29,548, similarly inhibited LPS-primed pulmonary hypertension and edema after PAF-stimulation. These studies indicate that LPS primes the lung for enhanced injury in response to the physiologic mediator PAF by amplifying the synthesis and release of thromboxane in lung tissue.     

输血相关急性肺损伤及其预防与控制策略的研究进展

输血相关急性肺损伤(TRALI)是指输血后6h内发生的急性肺损伤(ALI),是输血导致患者死亡的主要原因之一.目前对TRALI发病机制的假说包括“二次打击”学说与“阈值模型”学说等.超过80％ TRALI是由输注的血液制品中含特异性抗人类白细胞抗原(HLA)或人类中性粒细胞抗原(HNA)抗体介导的,并且导致TRALI发生的血液制品,主要来源于有多次妊娠史的女性献血者.目前,多个国家实行以男性献血者为主体,供应高血浆含量血液制品的临床预防、控制TRALI策略,以效降低TRALI发生率.笔者拟就TRALI的定义、发病机制、诊断、预防控制策略进行综述.     

内毒素性急性肺损伤大鼠肺HO-1的表达及其意义

目的观察内毒素(LPS)性急性肺损伤(ALI)大鼠肺组织血红素氧合酶-1(HO-1)的表达,探讨其意义。方法18只SD大鼠随机均分为ALI、锌原卟啉(ZnPP)预处理和正常对照3组,尾静脉注射给药。ALI组注入LPS 5 mg/kg,对照组注入生理盐水,ZnPP预处理组注入ZnPP 10μmol/kg 10 min后再注入LPS 5 mg/kg,各组注入液体总量相同。3 h后腹主动脉放血处死大鼠,生理盐水肺灌洗,取左肺制作组织匀浆,TRIZOL法提取总RNA后,用半定量逆转录聚合酶链反应(SqRT-PCR)测定HO-1 mRNA;另取右下肺制作病理切片,光镜观察并盲法评分比较肺组织学变化。结果静脉注入LPS后大鼠肺组织HO-1 mRNA的表达明显上调(P<0.05),肺损伤严重,评分显著增加;ZnPP预处理组ALI大鼠肺组织HO-1 mRNA的表达明显受抑,肺损伤更严重,评分更高(P<0.05);直线相关分析显示,HO-1 mRNA的受抑程度与损伤评分呈显著负相关(P<0.05)。结论内毒素性ALI肺组织表达上调的HO-1对肺损伤有一定的保护作用。     

急性肺损伤时肺部微环境介导的细胞代谢变化的研究进展

急性肺损伤（ALI）是临床上常见的肺部病变之一,病理表现为严重的肺水肿和透明膜形成,引起肺内微环境的改变。代谢学是通过监测生物体内源性代谢产物的变化（如糖类、脂类和氨基酸）,来反映机体的生理或者病理状态。鉴于人体肺部的代谢活跃,近年来大量研究表明,肺部微环境介导的细胞代谢学变化对于ALI的发生具有重要意义,并为ALI患者的早期预警、诊断及其治疗提供了一种崭新的手段。本文就细胞代谢改变在ALI中的应用及其研究进展做简要综述。     

大黄对急性肺损伤大鼠热休克蛋白70表达的影响

目的探讨脂多糖(LPS)致急性肺损伤(ALI)中热休克蛋白70(heatshockprotein,HSP)的表达以及大黄对ALI的保护作用机制。方法用Wistar大鼠复制ALI的动物模型,动物随机分成四组:对照组、ALI组、大黄预防用药组、大黄治疗用药组,每组15只。大黄采用腹腔注射给药,分别于注射LPS或生理盐水后2h处死动物。用HE染色观察组织病理学改变,对ALI组和大黄用药组测定肺系数和动脉血氧分压(PaO2),并应用免疫组织化学和蛋白印迹方法检测组织中HSP70的表达。结果ALI组肺间质水肿,肺泡腔内可见大量中性粒细胞浸润和血浆蛋白渗出,肺血管内皮细胞损伤。ALI组HSP70的表达量较少,大黄用药组HSP70表达量增强。大黄用药组肺系数测定明显降低,PaO2明显升高。ALI组肺系数测定升高,PaO2降低。结论大黄对ALI的肺组织起保护作用,并且预防组强于治疗组。大黄能增加LPS诱导ALI组织中HSP70的表达,表明大黄对ALI的肺组织起保护作用与HSP70相关。     

内毒素致急性肺损伤大鼠肺组织信号转导和转录激活因子1的调控作用

目的 探讨信号转导和转录激活因子1(STAT1)在内毒素致急性肺损伤(ALI)大鼠肺组织中的表达及其调控作用.方法 静脉注射内毒素脂多糖(LPS)制备大鼠ALI模型.将动物随机分为对照组、LPS组、地塞米松(DEX)干预组;DEX干预组灌胃DEX 0.135 mg/kg,对照组和LPS组分别灌胃等量生理盐水,连用5 d后LPS组和DEX干预组经尾静脉注射LPS 5 mg/kg,对照组以生理盐水1 ml替代.于致伤后1、2、4、8、16 h各处死6只大鼠,取肺组织,用蛋白质免疫印迹法(Western blotting)测定STAT1表达的动态变化,光镜下观察肺组织病理学改变.结果 与对照组比较,LPS组STAT1的活化从1 h开始增高,4 h达高峰,然后逐渐下降;2、4、8 h时STAT1表达显著升高(P均<0.01);DEX干预组STAT1表达趋势同LPS组,但2、4、8 h时STAT1表达显著低于LPS组(P均<0.05).结论 内毒素致ALI中存在STAT1异常表达;STAT1参与了肺组织炎症的形成.     

输血相关急性肺损伤大鼠模型建立及肺组织病理研究

目的 建立输注人类血浆大鼠输血相关急性肺损伤(TRALI)模型并分析其肺组织病理特点.方法 将分离存储21 d后人AB型全血中的血浆,经静脉输注给经脂多糖预处理后的雄性Sprague Dawley大鼠,建立TRALI 模型;分析大鼠肺组织病理及湿干比变化.结果 输注了从存储后人全血中分离血浆的大鼠成功建立起TRALI模型,大鼠肺组织出现肺泡间隔增厚、肺泡内纤维蛋白浸润、肺泡内出血、支气管壁增厚等病理变化,肺组织湿干比增高等改变.结论 所建立的输注(人)存储后全血中分离的血浆的TRALI大鼠模型具有可行性、实用性与稳定性等特点,为诊断和治疗TRALI提供了实验基础.     

Protective effects of aerobic exercise on acute lung injury induced by LPS in mice

Introduction

The regular practice of physical exercise has been associated with beneficial effects on various pulmonary conditions. We investigated the mechanisms involved in the protective effect of exercise in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI).

Methods

Mice were divided into four groups: Control (CTR), Exercise (Exe), LPS, and Exercise + LPS (Exe + LPS). Exercised mice were trained using low intensity daily exercise for five weeks. LPS and Exe + LPS mice received 200 µg of LPS intratracheally 48 hours after the last physical test. We measured exhaled nitric oxide (eNO); respiratory mechanics; neutrophil density in lung tissue; protein leakage; bronchoalveolar lavage fluid (BALF) cell counts; cytokine levels in BALF, plasma and lung tissue; antioxidant activity in lung tissue; and tissue expression of glucocorticoid receptors (Gre).

Results

LPS instillation resulted in increased eNO, neutrophils in BALF and tissue, pulmonary resistance and elastance, protein leakage, TNF-alpha in lung tissue, plasma levels of IL-6 and IL-10, and IL-1beta, IL-6 and KC levels in BALF compared to CTR (P ≤0.02). Aerobic exercise resulted in decreases in eNO levels, neutrophil density and TNF-alpha expression in lung tissue, pulmonary resistance and elastance, and increased the levels of IL-6, IL-10, superoxide dismutase (SOD-2) and Gre in lung tissue and IL-1beta in BALF compared to the LPS group (P ≤0.04).

Conclusions

Aerobic exercise plays important roles in protecting the lungs from the inflammatory effects of LPS-induced ALI. The effects of exercise are mainly mediated by the expression of anti-inflammatory cytokines and antioxidants, suggesting that exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ALI.     

内毒素肺损伤小鼠肺内清道夫受体A表达的变化

目的 观察内毒素肺损伤发病中小鼠肺组织及肺泡巨噬细胞(AM)清道夫受体A(SR-A)表达的变化.方法 腹腔注射内毒素脂多糖(LPS)复制小鼠急性肺损伤模型,实验分为LPS致伤后0.5、1、2、4和8 h组及对照组,用小鼠AM株J774A.1细胞作体外实验,分为LPS作用后0.5、1、2、4和8 h组及无血清培养液对照组.用免疫组化及流式细胞仪观察分析小鼠肺组织及AM、J774A.1细胞的SR-A表达及分布.结果 LPS各组小鼠动脉血氧分压(PaO2)均明显低于对照组,且肺湿/干重(W/D)比值明显高于对照组(P均＜0.01).对照组小鼠肺组织除支气管上皮细胞、淋巴细胞无SR-A表达外,AM、肺血管内皮细胞、血管平滑肌细胞、肺泡上皮细胞、中性粒细胞胞膜及胞质均有SR-A表达.LPS致伤后0.5 h即可观察到肺组织SR-A免疫组化染色弱于对照组,并且随着致伤时间延长,染色逐渐变浅,表明内毒素肺损伤发病中肺内SR-A表达减少.用J774A.1细胞作体外实验也发现类似结果,以4 h和8 h组降低最为显著.流式细胞仪检测AM及J774A.1细胞的SR-A表达与免疫组化染色结果相符,且细胞膜SR-A下降较细胞总SR-A显著.结论 内毒素肺损伤小鼠肺组织及AM的SR-A表达减少,其表达变化可能与内毒素作用有关.     

角化细胞生长因子对内毒素诱导急性肺损伤的保护作用

目的 初步研究角化细胞生长因子(KGF)对脂多糖(LPS)诱导大鼠急性肺损伤(ALI)的保护作用及可能的机制.方法 将36只SD大鼠按随机数字表法分为3组,每组12只.模型组尾静脉注射LPS 5 mg/kg建立ALI动物模型.对照组和KGF组注射等量生理盐水.KGF组在注射LPS后气道给予KGF 5 mg/kg.8 h后处死各组大鼠观察肺组织病理改变,并测量肺血管通透性、肺上皮细胞通透性、肺湿/干重(W/D)比值以及Ⅱ型肺泡上皮细胞(ATⅡ)增殖、修复功能改变.结果 光镜下观察显示KGF可有效减轻LPS所致ALI的肺组织病理改变,表现为肺血管充血、水肿减轻,几乎无炎性细胞浸润.与模型组比较,KGF组肺血管通透性[(0.026±0.049)%比(0.087±0.027)%]和肺泡上皮通透性[(0.692±0.017)%比(0.931±0.029)%]及W/D比值(4.778±0.243比6.869±0.153)均明显降低(P<0.05或P<0.01),ATⅡ细胞增殖及修复功能则明显提高[ATⅡ数量(个):6.083±1.781比4.666±1.923,损伤面积(mm2):2.946±0.453比6.181±0.975,P<0.05和P<0.01].结论 KGF可减轻LPS所致ALI,其机制可能是通过增强ATⅡ细胞的增殖及修复能力从而起到有效的保护作用.     

血管紧张素Ⅱ在急性肺损伤大鼠循环及肺组织中的表达

目的 研究大鼠急性肺损伤时循环及肺组织血管紧张素Ⅱ(AngⅡ)含量的变化,探讨AngⅡ在急性肺损伤发病中的作用.方法 清洁级SD大鼠30只,随机分为正常对照组(n=6)和模型组(n=24),模型组又按注射脂多糖(LPS)后3、6、9、12 h四个时间点分成4组,每组6只.分别于静脉注射LPS后各分组时间点观察大鼠一般情况、血压、动脉血气分析、肺组织湿质量/干质量(W/D)比值、肺组织病理改变,放免法测定血浆及肺组织AngⅡ的含量的变化,所有观察指标采用单因素方差分析与正常对照组比较.结果 与正常对照组比较,pH值和动脉血氧分压显著降低(P＜0.05),而二氧化碳分压及肺W/D比值均显著高于对照组(P＜0.05),病理形态学积分分析显示肺组织受损(P＜0.01).ALI大鼠血浆及肺组织AngⅡ均升高(P＜0.05),其中血浆AngⅡ在9 h时点达峰值,而组织Ang Ⅱ浓度在各观察时间点持续上升.结论 ALI时肺组织和血中Ang Ⅱ大量释放,提示ALI时伴有全身及肺局部肾素-血管紧张素系统的激活.     

The effect of tumor necrosis factor-alpha on microvascular permeability in an isolated,perfused lung

This study examines the hypotheses that TNF-alpha causes a dose-dependent increase in the microvascular permeability of ex vivo buffer perfused lungs that is quantitatively similar to that caused by lipopolysaccharide (LPS) or thromboxane A2 (TxA2). We also postulated that TNF-alpha potentiates the effect of interleukin-1beta (IL-1beta) or TxA2 receptor activation on pulmonary microvascular permeability. Lungs harvested from Wistar rats were perfused ex vivo with Krebs-Henseleit buffer containing 0, 10, 100, or 1000 ng/mL recombinant rat TNF-alpha. Twenty minutes later pulmonary microvascular permeability was determined by measuring the capillary filtration coefficient (Kf) using a gravimetric technique. The effect of TNF-alpha (100 ng/mL) on pulmonary Kf was compared with that of lungs exposed to LPS (400 microg/mL; E. coli 0111:B4) or a TxA2 receptor agonist (U-46619; 7 x 10(-8)). In other experiments, perfused lungs were exposed to TNF-alpha plus IL-1beta (1 ng/mL) or TNF-alpha plus U-46619 after which Kf was measured. Exposure of ex vivo buffer perfused lungs to 10-1000 ng/mL TNF-alpha had no effect on Kf whereas LPS and U-46619 was associated with a two- and six-fold increase in Kf, respectively (P < 0.05). The Kf of lungs exposed to TNF-alpha plus IL-1 was similar to that of lungs exposed to TNF-alpha alone. Lastly, the Kf of lungs exposed to TNF-alpha plus U-46619 was not different than that of lungs exposed to U-46619 alone. In conclusion, TNF-alpha at least when administered for a relatively brief period of time does not affect microvascular permeability in an isolated, buffer-perfused lung model.     

Transfusion reactions: newer concepts on the pathophysiology, incidence, treatment, and prevention of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. TRALI presents as acute lung injury (ALI) within 6 hours after blood product transfusion. Diagnosing TRALI requires a high index of suspicion, and the exclusion of circulatory overload or other causes of ALI. The pathophysiology of TRALI is incompletely understood, but in part involves transfusion of certain anti-neutrophil antibodies, anti-HLA antibodies, or other bioactive substances, into susceptible recipients. Recent studies have identified both recipient and transfusion risk factors for the development of TRALI. This article describes these TRALI risk factors, as well as diagnosis, treatment and prevention strategies.