急性肺水肿动物模型复制

目的—探讨氯化氨诱发大鼠肺水肿动物模型效果和机理。方法—将实验大鼠随机分为对照组、氯化氨组,腹腔注射方法注入6%氯化氨(♀:6~8 ml/kg,♂:9~12 ml/kg),观察动物的一般情况、肺系数计算及病理切片,确定建立大鼠肺水肿动物模型。结果—氯化铵能引起大鼠肺水肿,其临床表现有明显特点。结论—氯化铵诱发的肺水肿模型,临床症状典型,方法简单,经济易行且重复性好,能为教学、临床、科研提供较为理想的动物模型。     

The Effect of TIP on Pneumovirus-Induced Pulmonary Edema in Mice

Background

Pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure. In this study we determined whether treatment with TIP (AP301), a synthetic cyclic peptide that mimics the lectin-like domain of human TNF, decreases pulmonary edema in a mouse model of severe human RSV infection. TIP is currently undergoing clinical trials as a therapy for pulmonary permeability edema and has been shown to decrease pulmonary edema in different lung injury models.

Methods

C57BL/6 mice were infected with pneumonia virus of mice (PVM) and received TIP or saline (control group) by intratracheal instillation on day five (early administration) or day seven (late administration) after infection. In a separate set of experiments the effect of multiple dose administration of TIP versus saline was tested. Pulmonary edema was determined by the lung wet-to-dry (W/D) weight ratio and was assessed at different time-points after the administration of TIP. Secondary outcomes included clinical scores and lung cellular response.

Results

TIP did not have an effect on pulmonary edema in different dose regimens at different time points during PVM infection. In addition, TIP administration did not affect clinical severity scores or lung cellular response.

Conclusion

In this murine model of severe RSV infection TIP did not affect pulmonary edema nor course of disease.     

New Developments in the Pathogenesis of Smoke Inhalation-Induced Pulmonary Edema

Smoke inhalation causes most of the deaths in fire-related injuries, with pulmonary edema as a major determinant in the outcome of smoke-inhalation injury. The pathophysiology of pulmonary edema is thought to be related to the products of incomplete combustion. Damage to the integrity of the alveolar epithelium is one of the determinants of the development of smoke-induced pulmonary edema. In recent studies using lung clearance of aerosolized pentetic acid (DTPA [diethylenetriaminepentaacetic acid]) labeled with technetium Tc 99m to assess the permeability of the alveolar epithelium, several factors were identified that may increase a person''s susceptibility to smoke-induced acute lung injury. These are increased initial alveolar permeability and alterations in the number and activity of alveolar macrophages. Clinical measurement of ^99mTcDTPA clearance may provide a sensitive and convenient method for the early detection and serial assessment of smoke-induced alveolar epithelial permeability changes.     

波生坦对高原性肺水肿的治疗作用

目的:探讨波生坦对高原性肺动脉高压的治疗作用及其对NO的影响.方法:SD大鼠随机分为:正常组,安慰剂组和波生坦.除正常组外,其他组置于减压中,8h/d,持续6周.自第4周起,安慰剂组和波生坦组的大鼠在低压低氧前分别给与生理盐水或波生坦灌胃.测定各组大鼠的平均肺动压(mPAP)、右心室肥厚指数(RV/LV+S%)、肺系数;测定各组大鼠动脉血和肺组织中NO的含量以及肺组织中NOS的活性.结果:和正常组相比,安慰剂组大鼠的mPAP,RV/LV+S%和肺系数显著升高;波生坦能显著抑制RV/LV+S%和肺系数的升高,并使mPAP下降至正常组水平.安慰剂组大鼠动脉血及肺组织中NO的含量和肺组织中NOS的活性都明显降低于正常组;波生坦治疗组大鼠动脉血和肺组织中NO的含量以及肺组织中NOS的活性较安慰剂组都显著升高.结论:波生坦通过增加低压低氧大鼠体内NOS的活性和NO的含量,来发挥其治疗高原性肺水肿的作用.     

油酸诱导小型猪肺水肿模型的建立

目的制备油酸诱导小型猪肺水肿的动物模型,便于进行肺水肿的发病机制和相关治疗的研究。方法家养小型猪20只麻醉后随机分A、B两组,A组（n=10）为对照组,B组（n=10）为油酸组（油酸0.15 mL/kg经动物耳缘静脉缓慢注射）,观察两组动物肺组织病理改变、计算肺含水量及肺湿干重比。结果B组动物注射油酸后肺部出现明显的肺水肿病理改变,肺湿/干重比及肺含水量的值明显高于A组（P〈0.05）。结论本实验成功复制油酸诱导小型猪肺水肿动物模型,其病理组织切片符合肺水肿的典型病变。     

A Peptide to Reduce Pulmonary Edema in a Rat Model of Lung Transplantation

Background

Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself.

Methods

We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting.

Results

XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host.

Conclusions

In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation.     

呼吸机无创通气治疗急性心源性肺水肿临床研究

目的探讨大型多功能呼吸机及双相气道正压通气呼吸机治疗急性心源性肺水肿的临床价值。方法将48例急性心源性肺水肿患者分为无创通气治疗组（24例）和对照组（24例）,观察治疗前、后1h两组的血气分析及相关的症状、体征及病情缓解分值并进行统计学配对比较处理。结果治疗前各匹配组分析P〉0.05,说明两组基础病情具有可比性;治疗后1 h动脉血氧饱和度、血氧分压、呼吸频率、心率及缓解积分各组比较P〈0.01。结论表明治疗组较对照组的心肺功能改善更明显,由此表明该方法有极高的临床应用价值。     

肺泡上皮细胞钠-钾ATP酶与海水淹溺型肺水肿

钠-钾ATP酶(Na -K -ATPase)对于维持胞质渗透压和细胞容积的相对稳定以及细胞内pH的稳定具有重要的生理意义.肺泡上皮具有阻止液体进入肺泡腔内和主动清除肺泡腔内液体的作用,是抵抗肺泡性肺水肿形成的一道重要屏障.这一功能的完成有赖于Ⅱ型肺泡上皮细胞对钠离子的主动转运和分布于Ⅰ型、Ⅱ型肺泡上皮细胞的特殊水通道,而钠离子的主动转运依靠钠-钾ATP酶来完成.海水淹溺型肺水肿(PE-SWD)是以低氧血症及代谢性酸中毒为主要病理生理学特点的临床病症.PE-SWD发生时,Na -K -ATPase活性的改变直接影响到细胞膜外Na 、K 、等离子的浓度和分布,既是造成PE-SWD发生的多种因素所引起的直接恶果,又是促进PE-SWD不断发生的继发性原因.因此认识肺泡上皮细胞钠-钾ATP酶在PE-SWD发病中的作用对于PE-SWD的治疗具有重要意义.本文就钠-钾ATP酶的功能、结构、调节机制及钠-钾ATP酶在PE-SWD发病中的作用作一综述.     

重度颅脑损伤合并神经原性肺水肿机械通气的观察与护理

目的：探讨重型颅脑损伤合并神经原性肺水肿（NPE）病人机械通气的护理经验,提高此类病人的治疗成功率。方法：回顾性分析2000年～2007年18例颅脑损伤患者合并NPE的临床护理资料,对这些患者进行了机械通气治疗,观察和总结护理的临床效应。结果：18例患者中肺水肿消退11例,死亡7例。11例存活患者经过随访,死亡4例,植物生存1例,重残1例,中残2例,好3例。结论：重型颅脑损伤合并NPE预后不良,死亡率高;机械通气是治疗NPE的有效方法,正确积极的护理可提高患者的治愈率。     

Interactions among Vascular-Tone Modulators Contribute to High Altitude Pulmonary Edema and Augmented Vasoreactivity in Highlanders

Background

The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f).

Methodology/Principal Findings

All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO₂) and mean arterial pressure (MAP) and biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5-HT), 8-iso-prostaglandin F2α (8-isoPGF2α), endothelin-1 (ET-1), plasma renin activity (PRA), plasma aldosterone concentration (PAC), superoxide dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p<0.0001, each), whereas SOD activity and NO level were significantly lower in HAPE-p than HAPE-f (p≤0.001). Furthermore, ADMA, 5-HT, 8-isoPGF2α, NO levels and PAC were significantly higher (p<0.0001), whereas ET-1 level significantly (p<0.0001) and SOD activity non-significantly (p>0.05) lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO₂ inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009). MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p≤0.004). A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001), whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p≤0.004), with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05).

Conclusions/Significance

The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners.