部分液体通气对无心跳供体肺的保护作用

目的 观察部分液体通气对无心跳供体(NHBD)肺的保护作用.方法 36只清洁级SD大鼠随机分为3组:氧气组(C组)、盐水组(B组)和部分液体通气组(A组).建立NHBD肺模型后行机械通气2h并监测大鼠气道压,2h后测量P-V曲线,切除大鼠左肺下叶,观察供体肺病理特点.行右肺支气管灌洗,测量灌洗液中肺表面活性物质相关蛋白B、C(SP-B、SP-C)的浓度.切除大鼠右肺上叶,并进一步行SP-B、SP-C的实时定量聚合酶链反应(Real-time PCR)检测.结果 A组大鼠动态顺应性和静态顺应性在2h热缺血期间都优于B和C组(P＜0.05);病理组织评分A组优于B组和C组(P＜0.05);肺泡灌洗液酶联免疫吸附试验(ELISA)检测和肺组织的Real-time PCR检测说明SP-B和SP-C蛋白和RNA含量差异有统计学意义,其中A组含量明显高于B组和C组(P＜0.05).结论 部分液体通气可以对热缺血期间供肺的肺功能和肺组织起到很好的保护作用,并对SP-B和SP-C有较好的保护作用.     

白细胞介素-8与肺表面活性蛋白-A、B在急性肺损伤中作用关系的研究

目的：分析急性肺损伤（ALI）时白细胞介素-8（IL-8）与肺表面活性蛋白（SP）-A、B的含量变化及其相互关系,探讨急性肺损伤的发病机制。方法：Wistar大鼠30只,随机分为生理盐水对照组6只和ALI组24只,采用上腔静脉注入油酸的方法复制ALI动物模型。ALI组于制模后1、2、4、6 h收集血清及支气管肺泡灌洗液（BALF）,用放免法测定血清IL-8含量变化,采用酶联免疫吸附法（ELISA）检测肺泡灌洗液中SP-A、B含量的变化,并与对照组进行比较。结果：ALI大鼠血清中IL-8水平显著上升（P〈0.05）,而BALF中SP-A、B含量显著降低,血浆IL-8含量升高与BALF中SP-A、SP-B下降呈显著负相关（r值分别-0.524和-0.425,P均〈0.05）。结论：ALI时IL-8含量升高与SP-A、B含量的降低有显著的相关性,炎症细胞因子IL-8可能通过影响SP-A、SP- B的表达发挥致病作用。     

腺苷注射液治疗胸部撞击后肺挫伤的作用机制

目的探讨腺苷注射液对撞击所致肺挫伤的治疗作用机制。方法选取30只健康日本大耳兔,随机分为对照组和腺苷注射液治疗组,每组15只。用BIM-Ⅱ型生物撞击机制备兔肺挫伤模型,分别于撞击前10min和撞击后1、3、5、7h采集颈总动脉血,采用硫代巴比妥酸(TBA)比色法检测丙二醛(MDA)浓度,ELASA试剂盒检测白介素-10(IL-10)浓度。于伤后7h取下兔右肺,采用比色法检测肺组织中髓过氧化物酶(MPO)含量,ELISA法检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子α(TNF-α)含量,并测定肺泡表面活性物质水平。解剖并观察兔肺大体和显微病理学改变。结果对照组受伤后不同时间点的血浆MDA浓度、肺组织中MPO含量、BALF中TNF-α浓度和中性粒细胞弹性蛋白酶(NE)活性均较腺苷组显著升高(P0.05或P0.01),而腺苷治疗组血浆IL-10浓度和BALF中总磷脂(TPL)含量均较对照组明显升高(P0.05或P0.01)。对照组肺组织实变明显,肺泡结构破坏,大量中性粒细胞(PMNs)为主的炎症细胞及红细胞、血小板等聚集,相邻肺泡间质水肿增厚,线粒体肿胀空泡化,微绒毛和板层小体稀少;腺苷组肺泡结构基本正常,可见腺苷治疗组肺组织的病理损害明显较对照组减轻。结论腺苷注射液对肺挫伤有治疗作用,其机制可能与调节肺挫伤早期炎症因子浓度有关。     

用表面活性剂替代疗法治疗成人肺机能不全是否有效

表面活性物质是一种复杂的由脂类和蛋白质组成的混合物,其成分在哺乳动物体内相当稳定。对支气管肺泡灌洗液进行分析,可发现表面活性物质的组成中90％是脂类,10％是蛋白质。脂类的主要成分是饱和二棕榈酰磷酸酰胆碱,其次是游离胆固醇和负磷脂。蛋白质中,约50％是灌洗液污染物的血清蛋白,其余由4种表面活性剂相关蛋白(SP)组成:SP-A、SP-B、SP-C和SP-D。其中,SP-A和SP-D具有水溶性,易从脂类中分离,不仅能增强细菌和病毒的吞噬作用,还对Ⅱ型肺泡细胞产生调节作用。     

丝裂原活化蛋白激酶在机械通气过程中对肺表面活性物质及特异蛋白基因表达的影响

目的 丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)在机械通气过程中对肺表面活性物质及特异蛋白基因表达的影响和可能机制. 方法 采用健康成年雄性Sprague-Dawley大鼠48只,体重250 g～320 g.采用3％戊巴比妥35 mg/kg～40 mg/kg腹腔注射麻醉后行气管切开置管术,完全随机分组方法分为6组(每组8只):①C组(对照组,麻醉后仅做气管切开不做机械通气)；②LV组[正常通气组,潮气量(Vt):6ml/kg,余同过度通气组]；③HV组[过度通气组,Vt:40 ml/kg,呼吸频率(RR)40次/min,吸呼比(I∶E)1∶2～1∶3,呼气末正压通气(PEEP) =0,吸入氧浓度(FiO2)21％,通气4 h]；④SP600125组(SP600125+ HV组,高潮气量通气前30 min给予MAPK拮抗剂SP600125)；⑤PD98059组(PD98059+ HV组,高潮气量通气前30 min给予MAPK拮抗剂PD98059)；⑥SB203580组(SB203580+ HV组,高潮气量通气前30 min给予MAPK拮抗剂SB203580).机械通气4h后(对照组气管切开后4h),采用RT-PCR方法测定肺表面活性蛋白(SP)-A、B、C和RTI40 mRNA表达量. 结果 ①与C组比较,LV组、HV组大鼠肺组织中RTI40表达均增加(P＜0.05),而HV组、SP600125 +HV组及SB203580+HV组肺组织中SP-A、SP-C表达均减少(P＜0.05),LV组中和PD98059+HV组中的SP-A、C变化均无统计学意义(P＞0.05)；②与HV组比较,SP600125+HV组、PD98059+HV组、SB203580+HV组肺组织中SP-A、C基因表达增加(P＜0.05),RTI40基因表达降低(P＜0.05)；③SP-A、C基因表达量在PD98059+HV组较SP600125+HV组、SB203580+HV组升高(P＜0.05)；④SP-B在各组中变化无统计学意义(P＞0.05). 结论 高潮气量机械通气致肺上皮细胞特异蛋白SP-A、C基因表达下降和RTI40基因表达上调,而MAPK拮抗剂可以防止该现象发生,提示MAPK影响呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)过程中对肺上皮细胞的分泌功能.     

L-精氨酸对内毒素诱导急性肺损伤大鼠肺表面活性物质的影响

目的 评价L-精氨酸对内毒素(LPS)诱导急性肺损伤大鼠肺表面活性物质的影响.方法 健康雄性SD大鼠48只,随机分为4组:正常对照组(C组,n=16)、LPS组(n=16)、LPS 3 h+L-精氨酸治疗组(L1组,n=8)和LPS 6 h+L-精氨酸治疗组(L2组,n=8).LPS组、L1组和L2组静脉注射LPS 5mg/kg,C组给予等容量生理盐水.L1组和L2组分别于给予LPS后3 h或6 h腹腔注射L-精氮酸500 mg/kg.L1组和L2组于给予L-精氨酸后3 h(C组和LPS组分别于给予生理盐水或LPS后6、9 h)取8只大鼠,取肺组织,测定表面活性物质结合蛋白A(SP-A)mRNA的表达水平、肺泡灌洗液(BALF)中总磷脂(TPL)和总蛋白(TP)浓度,光镜下观察肺组织病理学结果.结果 与C组比较,LPS组SP-A mRNA表达下调,BALF中TPL浓度降低,TP浓度升高(P＜0.01).与LPS组比较,L1组SP-A mRNA表达上调,BALF中TPL浓度升高,TP浓度降低(P＜0.05或0.01);L2组上述指标差异无统计学意义(P＞0.05).L1组肺损伤程度轻于LPS组和L2组.结论 L-精氨酸可促进肺表面活性物质合成,从而对大鼠内毒素诱导急性肺损伤具有治疗作用.     

不同时间单肺通气对兔肺泡灌洗液中肿瘤坏死因子-α、白介素-8和肺组织表面活性蛋白-A表达的影响

目的 观察不同时间单肺通气(one lung ventilation,OLV)对兔支气管肺泡灌洗液中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白介素-8(interleukin-8,IL-8),以及肺组织表面活性蛋白-A(surfactant protein-A,SP-A)表达的影响.方法 选择新西兰大白兔60只.按完全随机分组方法随机均分为C组和O1、O2、O3、O4、O5组(每组10只).O1～O5组建立右肺OLV,分别给予OLV1、2、3、4、5h.各组中5只兔子完成OLV后立即处死,另5只兔子拔除各种管道自然养活24 h,分别测定左右肺灌洗液中细胞数、TNF-α、IL-8浓度和肺组织SP-A.结果 OLV时,与C组比较,O3～O5组左右肺细胞数均大于4.64±0.79 (P＜0.01);O4和O5组二氧化碳分压(PaCO2)高于43.6±5.7 (P＜0.01);O3～O5组左肺TNF-α值均升高大于101.90±18.65(P＜0.01),O4～O5组左肺IL-8值升高大于256.16±30.32(P＜0.01),O5组右肺TNF-α、IL-8值升高(P＜0.01).24h后,O4～O5组左肺细胞数仍高于7.5±1.9(P＜0.01);左肺IL-8值在O5组为214.60±76.74 (P＜0.01).左肺与右肺间的TNF-α和IL-8值在OLV时与24h后各时点比较均无统计学差异(P＞0.05).与C组比较,O1～O3组左肺SP-A表达均大于13.84±3.47(P＜0.01)、O1～O5组右肺SP-A表达均大于5.51±1.48 (P＜0.01),O4～O5组SP-A表达减少;24h后O1～05组左右肺SP-A表达均大于12.17±4.75(P＜0.01).结论 随着OLV时间延长,肺炎症反应明显及肺SP-A表达减少;在OLV超过3h,即使恢复双肺通气24 h后,肺损伤仍难以完全修复,应避免OLV时间过长.     

体外循环对肺表面活性蛋白A的影响

目的观察体外循环(CPB)对肺泡表面活性蛋白A(SP-A)组成的影响。方法以6周龄左右的猪为实验动物,常规建立CPB,于CPB前、CPB60min、120min及CPB结束3h以纤维支气管镜吸取支气管肺泡灌洗液(BALF),通过蛋白免疫印迹反应法测定SP-A。结果SP-A总量在CPB过程中明显下降,CPB60min和120min时与CPB前比较差别有统计学意义(P=0.045,0.017),但在CPB结束3h时基本恢复至CPB前水平;36.70ku组分在CPB过程中无明显变化,但在CPB结束3h明显增加(P=0.034);25.79ku组分在CPB过程中明显降低,在CPB后也未明显恢复(P=0.044,0.022)。结论在CPB过程中,SP-A总量减少,其不同组分的变化则不相同。     

吸入七氟醚、地氟醚对大鼠肺组织超微结构和肺表面活性物质的影响

目的观察不同吸入浓度七氟醚和地氟醚对大鼠肺组织超微结构及支气管肺泡灌洗液 (BALF)中肺表面活性物质相关蛋白-A(SP-A)、磷脂酰胆碱(PC)浓度的影响。方法雄性Wistar大鼠 50只,随机分为5组,每组10只,C组:单纯机械呼吸组;S1组和S2组:分别吸入1．0 MAC、1．5 MAC七氟醚4 b;D1组和D2组:分别吸入1．0MAC、1．5MAC地氟醚4 b。在相应时点处死大鼠,观察肺组织超微结构并测定BALF中SP-A和PC浓度。结果与C组比较,S1、S2、D1、D2组肺泡Ⅱ型上皮细胞微绒毛破坏程度较重,以D1、D2组改变更明显,板层体减少,并呈大量空泡化;BALF中SP-A、PC浓度下降 (P<0．01或0．05)。结论吸入1-0 MAC、1．5 MAC七氟醚或地氟醚4 h可降低肺泡Ⅱ型上皮细胞合成肺表面活性物质。     

肺癌支气管肺泡灌洗液中内皮抑素的表达

目的 探讨肺癌病人术前血清及支气管肺泡灌洗液(BALF)中内皮抑素(endostatin)表达情况,分析其与肿瘤临床病理特征和预后的关系.方法 酶联免疫吸附(ELISA)法检测57例肺癌及34例肺良性病变者术前血清及BALF中endostatin含量.结果 肺癌病人血清及BALF术前内皮抑素含量显著高于肺良性病变者,差异有统计学意义(P＜0.05).淋巴结及远处转移组术前内皮抑素含量明显高于无转移组(P＜0.05);肺腺癌病人外周血清及BALF中内皮抑素表达高于鳞癌、小细胞癌者;Ⅲ～Ⅳ期病人血清、BALF内皮抑素水平高于Ⅰ～Ⅱ期者(P＜0.01).肺癌病人内皮抑素在外周血清及BALF中的表达呈线性正相关(P=0.000).结论 肺癌病人血清及支气管肺泡灌洗液中内皮抑素含量明显高于良性病变者,且与肿瘤组织学类型、分化程度、TNM分期、淋巴结转移呈明显正相关,肺泡灌洗液中内皮抑素含量较血清中高且更敏感,可能有助于肺癌病人预后的评估及肿瘤分化程度判断.     

含抑肽酶低温灌注液减轻体外循环肺损伤

目的;研究体外循环期间低温保护液肺动脉灌注对肺脏的保护作用。方法;１２只杂种犬随机均分为２组。主动脉阻断后,对照组右肺动脉灌注４℃乳酸林格液,实验组灌注４℃肺保护液。开放主动脉后和停ＣＰＢ后５,３０,６０,９０分钟;分别取各组肺静脉血标本行生化分析,测定肺功能,并行组织学检查。     

CPB诱发犬急性肺损伤时肺组织转化生长因子β1 mRNA表达的变化

目的 观察CPB诱发犬急性肺损伤时肺组织转化生长因子β1(TGF-β1)mRNA表达的变化.方法 成年健康杂种犬36只,体重15～16 kg,随机分为2组(n=18):对照组(C组)和CPB组.CPB组制备CPB诱发急性肺损伤模型,C组除不进行CPB外,其余操作同CPB组.分别于CPB前(T0)、CPB停机后30 min(T1)、60 min(T2)时各处死6只犬,取肺组织,光镜下观察肺组织病理学结果,计算肺通透性指数(PPI),测定肺组织TGF-β1 mRNA表达和MDA含量.结果 C组肺组织结构清晰,未见炎性细胞浸润,肺泡壁光滑、完整,肺泡腔及间质无出血和渗出;CPB组肺泡腔内可见水肿液和中性粒细胞浸润,并可见大量的红细胞,肺泡隔增宽,局灶性肺不张.与C组比较,CPB组TGF-β1 mRNA表达上调,MDA含量和PPI升高(P<0.05或0.01).CPB组TGF-β1 mRNA表达水平与MDA含量和PPI呈正相关(MDA:r=0.867,P<0.01;PPI:r=0.821,P<0.01).结论 犬CPB后肺组织TGF-β1 mRNA 表达上调,可能是CPB诱发急性肺损伤发生发展的重要因素之一.     

Pulmonary artery perfusion with protective solution reduces lung injury after cardiopulmonary bypass

BACKGROUND: The inflammatory response and higher temperature of lung tissue during cardiopulmonary bypass can result in lung injury. This study was to evaluate the protective effect of pulmonary perfusion with hypothermic antiinflammatory solution on lung function after cardiopulmonary bypass. METHODS: Twelve adult mongrel dogs were randomly divided into two groups. The procedure was carried out through a midline sternotomy, cardiopulmonary bypass was established using cannulas placed in the ascending aorta, superior vena cava, and right atrium near the entrance of the inferior vena cava. After the ascending aorta was clamped and cardioplegic solution infused, the right lung was perfused through a cannula placed in the right pulmonary artery with 4 degrees C lactated Ringer's solution in the control group (n = 6) and with 4 degrees C protective solution in the antiinflammation group (n = 6). Antiinflammatory solution consisted of anisodamine, L-arginine, aprotinin, glucose-insulin-potassium, and phosphate buffer. Plasma malondialdehyde, white blood cell counts, and lung function were measured at different time point before and after cardiopulmonary bypass; lung biopsies were also taken. RESULTS: Peak airway pressure increased dramatically in the control group after cardiopulmonary bypass when compared with the antiinflammation group at four different time points (24 +/- 1, 25 +/- 2, 26 +/- 2, 27 +/- 2 cm H2O versus 17 +/- 2, 18 +/- 1, 17 +/- 1, 18 +/- 1 cm H2O; all p < 0.01). Pulmonary vascular resistance increased significantly in the control group than in the antiinflammation group at 5 and 60 minutes after cardiopulmonary bypass (1,282 +/- 62 dynes x s x cm(-5) versus 845 +/- 86 dynes x s x cm(-5) and 1,269 +/- 124 dynes x s x cm(-5) versus 852 +/- 149 dynes x s x cm(-5), p < 0.05). Right pulmonary venous oxygen tension (PvO2) in the antiinflammation group was higher than in the control group at 60 minutes after cardiopulmonary bypass (628 +/- 33.3 mm Hg versus 393 +/- 85.9 mm Hg, p < 0.05). The ratio of white blood cells in the right atrial and the right pulmonary venous blood was lower in the antiinflammation group than in the control group at 5 minutes after the clamp was removed (p < 0.05). Malondialdehyde were lower in the antiinflammation group at 5 and 90 minutes after the clamp was removed (p < 0.01 and p < 0.05, respectively). Histologic examination revealed that the left lung from both groups had marked intraalveolar edema and abundant intraalveolar neutrophils, whereas the right lung in the control group showed moderate injury and the antiinflammation group had normal pulmonary parenchyma. CONCLUSIONS: Pulmonary artery perfusion using hypothermic protective solution can reduce lung injury after cardiopulmonary bypass.     

Lung protection during total cardiopulmonary bypass by isolated lung perfusion: preliminary results of a novel perfusion strategy

BACKGROUND: The present pilot study was conducted to evaluate the effect of isolated short-term lung perfusion during cardiopulmonary bypass (CPB) on inflammatory response and oxygenation. METHODS: A total of 24 patients undergoing elective cardiac surgery with routine CPB were prospectively assigned to three groups. Group I (n = 7), control subjects receiving neither lung perfusion nor ultrafiltration; group II (n = 9), patients undergoing lung perfusion; and group III (n = 8), patients undergoing lung perfusion plus ultrafiltration. Lung perfusion consisted of single-shot hypothermic pulmonary artery perfusion with oxygenated blood. Proteins indicative of leukocyte activation and lung injury were measured in plasma and bronchoalveolar lavage fluid (BALF). The alveolar-arterial oxygen gradient (A-aDO2) and the oxygenation index (PO2/FiO2) were also determined. RESULTS: Oxygenation values were best preserved in group III, followed by group II. After CPB, elastase-alpha1-proteinase inhibitor complex had increased in plasma in all groups; in BALF it increased in groups I and II, but not in group III. Alpha2-macroglobulin increased significantly in BALF in group I but not in groups II and III. CONCLUSIONS: These preliminary results provide some evidence that single-shot hypothermic lung perfusion with oxygenated blood at the beginning of CPB may have a protective effect on the lungs, especially when combined with ultrafiltration.     

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass

BACKGROUND: Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS: Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS: All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS: This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.     

N-acetylcysteine reduces lung reperfusion injury after deep hypothermia and total circulatory arrest

OBJECTIVE: We hypothesized that the use of N-acetylcysteine would ameliorate the lung reperfusion injury observed after deep hypothermia and total circulatory arrest (DHTSA). METHODS: Experiments were carried out on 12 adult mongrel dogs of either sex weighing 25 to 30 kg. The animals were randomly divided into two groups of six animals each. All animals were cooled to an esophageal temperature of 15 degrees C during 30 minutes and underwent 60 minutes of DHTSA, followed by the reinstitution of cardiopulmonary bypass (CPB) and rewarming. Before rewarming, while 100 mL physiologic saline solution was added into the pump in group I, 50 mg/kg N-acetylcysteine(NAC) was given in group II. Heart rate, mean arterial pressure, pulmonary arterial pressure, left atrial pressure, central venous pressure, and cardiac output were recorded. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes (PMNs) count, lung tissue samples were taken before CPB and after weaning CPB. In addition, alveolar-arterial oxygen difference (AaDO(2))()for tissue oxygenation was calculated by obtaining arterial blood gas samples. Dynamic lung compliance (DLC) was measured before CPB and after CPB. RESULTS: MDA levels before CPB of 44.2 +/- 3.9 nmol/g tissue rose to 76.6 +/- 5.6 nmol/g tissue after weaning CPB in group I (p = 0.004). In group II also, the MDA levels increased from 43.5 +/- 4.2 to 57.4 +/- 5.6 nmol MDA/g tissue after weaning CPB (p = 0.006). The MDA increase in group II after CPB was found to be significantly lower than in group I (p = 0.006). The wet-to-dry lung weight ratio in the NAC group was 5.1 +/- 0.2, significantly less than in the control group (5.9 +/- 0.3), (p = 0.004). AaDO(2) significantly increased in the group I and II (p = 0.002 and p = 0.002, respectively); this elevation in group I was significant than in group II (p = 0.044). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups (p < 0.001). The increase in group I was significantly larger than group II (p < 0.001). CONCLUSIONS: Results represented in our study indicate that addition of NAC into the pump after DHTSA can reduce lung reperfusion injury.     

N-乙酰半胱氨酸对体外循环诱发犬肺损伤的影响

目的 探讨N-乙酰半胱氨酸对体外循环(CPB)诱发犬肺损伤的影响.方法 成年犬36只,雌雄不拘,体重15 ～ 16 kg,采用随机数字表法,将其随机分为2组(n=18):CPB组(C组)和N-乙酰半胱氨酸组(N组).右锁骨下动脉和右心房分别插管,制备CPB模型,N组于CPB前即刻静脉注射N-乙酰半胱氨酸150mg/kg,然后以20 mg·kg-1·h-1速率静脉输注至CPB结束后60 min;C组给予等容量生理盐水.分别于CPB前、CPB结束后30、60 min时采集动脉血样,进行动脉血气分析,计算呼吸指数和氧合指数;然后处死动物,取肺组织,测定MDA含量、SOD活性和转化生长因子-β1( TGF-β1) mRNA表达;光镜和电镜下观察肺组织病理学结果.结果 与C组比较,N组呼吸指数和肺组织MDA含量降低,氧合指数和肺组织SOD活性升高,TGF-β1 mRNA表达下调(P＜0.05或0.01),肺组织病理学损伤程度明显减轻.结论 N-乙酰半胱氨酸可减轻CPB诱发犬肺损伤,其机制与减轻脂质过氧化反应,下调肺组织TGF-β1表达有关.     

High oxygen concentration exacerbates cardiopulmonary bypass-induced lung injury

OBJECTIVE: To investigate the effect of ventilation with 100% oxygen on lung injury associated with surgery involving cardiopulmonary bypass (CPB). DESIGN: A prospective randomized study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing coronary artery bypass graft surgery with CPB. INTERVENTIONS: Patients were randomized to receive 100% oxygen (Oxygen group) or 50% oxygen (Air group) throughout surgery. During CPB, patients' lungs in the Air group were flushed with air and in the Oxygen group with 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Lung injury was evaluated by arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio and cytokine levels (tumor necrosis factor-alpha and interleukin-8) in blood and bronchoalveolar lavage fluid measured before and after CPB. The lowest PaO2-FIO2 value was observed after 40 minutes following the completion of CPB in both groups. PaO2-FIO2 values 6 hours after CPB were not different from baseline in the Air group but remained lower (359+/-63 mmHg and 298+/-78 mmHg; p = 0.013) in the Oxygen group. Blood cytokine levels rose during surgery in both groups. Bronchoalveolar lavage levels of interleukin-8 did not change, whereas tumor necrosis factor-alpha increased only in the Oxygen group (p = 0.035). CONCLUSIONS: A significant decrease of oxygenation was observed in the early post-CPB period in both groups of patients, with delay in recovery in patients treated with 100% oxygen. A larger increase of the proinflammatory cytokines was found in patients treated with 100% oxygen. High oxygen concentrations during surgery with CPB should be used only when specifically required.     

Does sodium nitroprusside reduce lung injury under cardiopulmonary bypass?

Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20–28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28°C core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 μg/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO₂) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0±5.3 nmol/g of tissue rose to 67.6±5.7 nmol/g of tissue after weaning from CPB in group I (P=0.028). In group II MDA values also increased from 43.1±4.3 to 52.4±5.7 nmol MDA/g of tissue after weaning from CPB (P=0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P=0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1±0.2, significantly lower than in the control group (6.8±0.4), (P=0.01). AaDO₂ increased significantly in group I (P=0.028). There was no statistically significant difference (P=0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P<0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass.     

Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which can result in acute lung injury known as "postperfusion syndrome." Neutrophil activation with concomitant serine protease release has been implicated in the pathogenesis of "postperfusion syndrome." Increased plasma levels of neutrophil elastase (NE) have been demonstrated in patients undergoing CPB, and it is well documented that both NE and matrix metalloproteinase-9 (MMP-9) have a synergistic role in pulmonary injury. We, therefore, hypothesized that plasma levels of MMP-9 would be elevated in patients after CPB. Human plasma was obtained after informed consent from eight patients undergoing CPB. Plasma was collected at the start of CPB, 5 minutes after the initiation of CPB, and at the termination of CPB (156 +/- 17 min). All samples were analyzed by both standard enzyme-linked immunosorbent assay (ELISA) and gelatin zymography for MMP-9 (free and total enzyme) concentration. Data were expressed as means +/-SE and assessed by analysis of variance (ANOVA). Plasma MMP-9 concentration was significantly increased at the end of CPB (191 +/- 30.4 ng/mL; p <.05) as compared to both the start of CPB (28.3 +/- 13.2 ng/mL) and 5 minutes after the initiation of CPB (44.3 +/- 15.4 ng/mL). Patients undergoing CPB show an increase in serum MMP-9 levels. Prior studies utilizing an animal model of "postperfusion syndrome" have shown that inhibition of MMP-9 and NE prevented pulmonary injury following CPB. The results of the current study suggest that such an approach may also have merit in the clinical setting of cardiopulmonary bypass.