乌司他丁对创伤失血性休克兔肺损伤的保护作用

目的 探讨乌司他丁对肺缺血-再灌注损伤的保护作用及其机制。方法 新西兰白兔30只,随 机分为假手术对照组、创伤失血性休克组和乌司他丁治疗组。动物模型用经股动脉放血使平均动脉压降至 (40±5)mm Hg(1 mm Hg=0.133 kPa).维持90 min后回输全部失血及等量乳酸林格液进行复苏。复苏后4 h 测定肺组织髓过氧化物酶(MPO)、肺泡灌洗液中中性粒细胞弹性蛋白酶(BALF-NE)活性、肺叶湿／干重比 及肺组织病理学改变。结果 休克组和乌司他丁治疗组MPO含量、BALF-NE活性以及湿／干重比均较假手 术对照组显著增高(P均<0.05),乌司他丁治疗组各指标均明显低于休克组(P均<0.05)。结论 蛋白酶抑 制剂乌司他丁在创伤失血性休克时能够抑制肺MPO和NE活性,降低肺组织湿／干重比,减轻缺血-再灌注 后的肺损伤。     

油酸致大鼠急性呼吸窘迫综合征氧化应激反应和纳洛酮的拮抗作用

目的探讨纳洛酮对油酸所致大鼠急性呼吸窘迫综合征治疗作用的可能机制。方法将30只健康的Wist—ar大鼠随机分为对照组、油酸组、纳洛酮组。由股静脉注入油酸0．1ml／kg建立ARDS模型，测定肺组织MDA、SOD含量，并计算左肺湿／干重比值．行肺组织病理学及超微结构观察。结果油酸组与对照组比较，左肺湿／干重比值、肺组织中MDA含量明显升高，SOD活性明显降低，肺组织出现明显病理损害，纳洛酮组动物肺损伤轻于油酸组。结论纳洛酮可抑制MDA升高．提高SOD活性．对实验性大鼠油酸型急性呼吸窘迫综合征有一定的治疗作用。     

应用荧光分光光度法测定血清及组织中阿霉素含量

目的探讨测定血清及组织中阿霉素含量的新方法。方法应用荧光分光光度计测定血清及组织中阿霉素含量及回收率。结果该方法能够较为准确的测定血清及组织中阿霉素含量，血清中阿霉素的平均方法回收率为100．19％，相对标准偏差5．96％；心、肝、肾、肺组织中阿霉素的平均方法回收率分别为97．61％、95．76％、96．01％、99．17％，相对标准偏差分别为6．03％、4．85％、5．87％、5．49％。结论应用荧光分光光度法测定血清及组织中阿霉素含量具有简单、方便、灵敏度高的优点，值得临床推广。     

热化疗对兔肝VX-2肿瘤血管渗透性影响的生物学机制

目的：在兔肝VX-2移植瘤模型基础上，进行在体肝肿瘤介入性热化疗，观察介入性热增敏与肝组织及肿瘤组织血管渗透性的关系，探讨介入性热化疗的生物学机制。方法：建立可供实验研究的兔Vx-2移植性肝癌模型30只，随机等分为3组(非灌注组、普通灌注组及热灌注组)，在X线监视下，经股动脉插管至肝动脉。进行灌注，灌注液为生理盐水(温度为60℃)，液量30mL，15min缓慢推注。灌注结束前5min，经导管推注10mg／L伊文思蓝(Evans Blue EB)，2mL／kg，非灌注组直接推注EB，灌注EB后置10min，取出肝畦用生理盐水灌注肝动脉冲洗血管中残留的EB。切取靠近肝门部的小块正常肝组织、瘤组织，称重后，放入1mL甲酰胺液中，置于50℃恒温水浴箱60h，提取液用722型光栅分光光度计测出A620 nm从标准曲线上测出相应的EB含量，以反映该组织毛细血管的渗透性。结果：肿瘤组织与肝组织的EB含量在3组中均有差别(P&;lt;0．05)；正常灌注组与非灌注组肝组织的EB含量、肿瘤组织的EB含量无明显差别(P&;gt;0．05)；热灌注组与非灌注组、正常灌注组肝组织的EB含量、肿瘤组织的EB含量有明显差别(P&;lt;0．05)。结论：介入热疗可以增加肝组织及肿瘤组织的血管渗透性。     

大鼠全肠道缺血再灌注后肠道组织和肠道外器官损伤的研究

目的：研究大鼠全肠道缺血再灌注（I／R）对肠道局部组织、肠道外器官的损伤和对细菌／内毒素移位的影响。方法：采用夹闭肠系膜前动脉（时间60min)技术复制肠道缺血再灌注损伤（GIRI）大鼠模型，观察：（1）门脉血和动脉血pH的变化；（2）检测血浆内毒素水平（鲎试剂定量试验法）和血浆肿瘤坏死因子（TNF－α）的变化；（3）检测不同组织的细菌移位量；（4）组织湿干重比值的变化。结果：成功复制了大鼠全肠道缺血再主损伤模型，肠道I／R损伤可引起：（1）I／R后3h，门脉血和动脉血pH明显下降（P均＜0．01），再灌注后24h后基本恢复正常；（2）TNF－α在再灌注后3h达峰值，明显高于缺血前水平（P均＜0．01）；（3）肠系膜各组淋巴结和肺、肝、肾组织匀浆均培养出大量细菌，与缺血前比较均有显著的统计学差异；（4）组织湿干重比值均显著高于缺血前水平。结论：全肠道缺血再灌注可损伤肠道黏膜屏障，引起细菌／内毒素移位，血浆TNF－α水平明显升高，肠道外器官损伤。     

老年多器官功能障碍综合征大鼠肿瘤坏死因子-α基因表达变化和意义

目的探讨组织中TNF—-α含量及mRNA表达变化在老年MODS中的作用。方法老年组（20月龄）和青年组（3月龄）SD大鼠各40只,建立油酸／脂多糖（OA／LPS）二次致伤老年MODS和青年MODS模型。观察对照组及伤后2、6、24h重要器官（肺、心、肝、肾）病理及功能的变化，ELISA法检测肺、心、肝和肾组织中TNF--α含量，RT—PCR法检测不同组织中TNF--αmRNA表达。结果OA／LPS二次致伤MODS模型，肺脏是损害出现最早也是最重的器官，致伤后2h青年组和老年组PaO2即显著下降至最低值（P〈0．01），伤后6h，心、肝、肾生化指标达峰值（P〈0．05～0．01），在相同时相点老年鼠脏器损害重于青年鼠（P〈0．05～0．01）。致伤2h后肺、心、肝和肾组织中TNF--αmRNA表达及蛋白含量均显著升高（P〈0．05～0．01），且持续高于正常对照组（P〈0．05～0．01），以肺组织中升高幅度最大，老年组显著高于同时相点青年组（P〈0．05）。结论OA／LPS致伤早期老年鼠肺组织中TNF--αmRNA表达及蛋白含量迅速升高，可能是老年MODS肺损伤出现最早且重于青年MODS的机制之一。     

镁与肺缺血-再灌注损伤

目的：观察硫酸镁对大鼠肺缺血-再灌注损伤的影响。 方法：实验于2003-05／2004-05河南科技大学医学院机能学实验室完成。将Wistar大鼠随机分为正常组、实验组(缺血-再灌注损伤组)及治疗组(硫酸镁组)，每组10只。戊巴比妥钠腹腔注射麻醉固定后，颈部气管切开插管，胸骨正中切开，尾静脉注射1mg／kg肝素90min后，实验组和治疗组在吸气末用无创伤血管夹阻断左肺门30min，放开后再灌注60min，制备大鼠原位肺缺血-再灌注损伤模型，治疗组于左肺门阻断前5min及再灌注前5min分别由尾静脉注入50g／L硫酸镁溶液20mg／kg，正常组手术方法同实验组和治疗组，但不阻断左肺门。各组在实验前后及灌注前后分别测定肺动脉氧分压及血氧饱和度，注射硫酸镁后测定血浆及肺匀浆超氧化物歧化酶及丙二醛含量，并计算肺组织湿于比值，观察肺组织病理变化。 结果：治疗组与实验组比较，肺湿干重比显著降低(t=5．548，P<0．01)，肺动脉氧分压及氧饱和度显著升高(t=3．132，7．150，P<0．01)；血清及肺匀浆超氧化物歧化酶活性显著增高(t=3．81，3．791，P<0．01)，丙二醛含量降低(t=13．35，3．32，P<0．01)。与正常组比较肺湿干重比显著升高(t=8．632，P<0．01)，动脉氧分压及氧饱和度显著降低(t=18．044，10．715，P<0．01)，血清及肺匀浆超氧化物歧化酶活性显著降低(t=4．93，11．33，P<0．01)，丙二醛含量增高(t=15．61，3．13，P<0．01)。实验组肺组织病理显示有大量炎性细胞浸润，有明显点块状出血坏死灶，间质明显水肿，治疗组仅见少量点状出血点及轻度炎性细胞浸润。 结论：镁制剂可通过清除氧自由基、抗氧化、减少脂质过氧化及激活腺苷酸环化酶，对大鼠肺缺血-再灌注损伤起保护作用。     

血浆血小板激活因子与急性肺损伤相关性及“神农33”注射 …

目的：探讨内毒素诱导急性肺损伤时血小板激活因子含量变化情况及“神农３３”注射液对ＰＡＦ及ＡＬＩ的影响。方法；给Ｗｉｓｔａｒ大鼠静脉注射ＬＰＳ，制成ＡＬＩ模型，采用反相高效液相色谱法检测ＬＰＳ攻击后１小时大鼠血浆ＰＡＦ含量，观察ＬＰＳ攻击后３小时大鼠肺湿，干重，光镜观察大鼠肺病理形态学变化。结果：ＡＬＩ组动物的肺湿重，湿干重比，肺含不量均明显高于正常对照组，肺病理组织这改变明显且严重。     

转化生长因子β 1对缺血再灌注损伤肺组织肿瘤坏死因子α及白细胞介素1 β含量的调节

背景：肺缺血再灌注时，大量聚集在肺内的白细胞被激活，释放多种细胞因子如肿瘤坏死因子α、白细胞介素1β等，进而介导再灌注损伤。新近研究发现，转化生长因子β1对犬移植肺组织缺血再灌注损伤有保护作用。目的：观察转化生长因子β1干预后，肺缺血再灌注损伤肺组织肿瘤坏死因子。和白细胞介素1β的含量变化。设计、时间及地点：随机对照动物实验，于2007-08／10在解放军第二军医大学附属长海医院胸心外科实验室完成。材料：清洁级SD大鼠30只，随机分为假手术组、缺血再灌注组、转化生长因子β1组，10只／组。转化生长因子β1为PeprotechINC．公司产品。方法：缺血再灌注组与转化生长因子β1组大鼠通过结扎肺门阻断肺循环1h、再灌注2h建立原位肺缺血再灌注损伤模型，假手术组大鼠仅以10^8丝线绕过肺门后不结扎。肺循环阻断前15min，各组颈静脉注射肝素抗凝，转化生长因子β1组同时注射10ug／kg转化生长因子β1。主要观察指标：再灌注2h后摘取左肺组织，光镜下观察肺组织形态变化，测定湿干重比及肺泡损伤指数，ELISA法检测肺组织匀浆中肿瘤坏死因子α和白细胞介素1β的含量。结果：30只大鼠均进入结果分析。假手术组肺组织无明显病理改变；缺血再灌注组可见明显的组织水肿及中性粒细胞浸润；转化生长因子β1组轻微组织水肿，少量中性粒细胞浸润。与假手术组比较，缺血再灌注组湿干重比及肺泡损伤指数均显著升高（P〈0．01）；与缺血再灌注组比较，转化生长因子β1组上述两项指标均明显降低（P〈0．05）。与假手术组比较，缺血再灌注组肿瘤坏死因子α及白细胞介素1β含量均显著升高（P〈0．01）；与缺血再灌注组比较，转化生长因子β1组上述两项指标均明显降低（P〈0．05，P〈0．01）。结论：转化生长因子β1能够明显改善肺缺血再灌注损伤，该作用与其有效抑制肿瘤坏死因子α及白细胞介素1β的表达密切相关。     

L-精氨酸对在体兔肺缺血-再灌注损伤影响的实验研究

【目的】探讨L精氨酸对兔肺缺血-再灌注损伤的影响。【方法】建立在体兔肺缺血-再灌注模型，随机分成三组：A组为假手术组、B组为缺血-再灌注组、C组为缺血-再灌注＋L-精氨酸处理组，每组7只。在再灌注60min行肺组织湿干比W／D值、丙二醛（MDA）、超氧化物歧化酶（SOD）含量测定和肺组织病理学检查。【结果】再灌注60min后C组肺组织W／D值、MDA含量较B组均明显降低（P〈0．05），而SOD、NO含量较B组明显升高（P〈0．05）；肺组织病理学检查示B、C组兔肺均有部分肺泡结构破坏，不同程度的炎症反应，其中C组炎症积分显著低于B组（P〈0．01）。【结论】L-精氨酸预处理，可减轻随后的缺血再灌注损伤。     

Pulmonary hypertension and edema induced by platelet-activating factor in isolated, perfused rat lungs are blocked by BN52021

The experimental intravenous administration of platelet activating factor (PAF) induces pulmonary hypertension and directly or indirectly increases capillary permeability. Selective PAF antagonists BN52021 and L652-731 have been shown to inhibit the action of PAF in vitro and in vivo. Using a unique isolated perfused rat lung model, we measured the effect of these PAF antagonists on PAF-induced pulmonary hypertension and edema. Isolated rat lungs were perfused with Krebs-Henseleit solution. The right and left pulmonary arteries were dissected so that they could be perfused selectively, permitting the use of one lung as an internal control for a specific pharmacologic challenge. Exposure of one lung to PAF induced an increase of perfusion pressure and wet/dry lung weight ratio in a dose-dependent manner compared with the control lung. The PAF antagonists attenuated the increase in perfusion pressure and wet/dry lung weight caused by PAF (0.75 micrograms) in a dose-dependent manner. In addition, prostaglandin F2 alpha induced an equivalent increase in pulmonary pressure without causing a similar increase in lung edema. PAF-induced pulmonary hypertension and the increase in wet/dry lung weight ratio appear to be PAF receptor-mediated processes, and the use of specific antagonists and this technique may be useful probes to determine the role of PAF in pathophysiologic states.     

无心跳供体肺移植大鼠模型的建立

背景:大量实验表明,供肺组织及肺血管功能在适当条件下可以保存,当供体心跳停止后,肺的气体交换系统可耐受热缺血60min。目的:建立一种简单有效的无心跳供体肺移植大鼠模型。方法:60只SD大鼠随机分为有心跳供体组、无心跳供体-缺血30min组和无心跳供体-缺血60min组,每组20只。有心跳供体组供体大鼠取供肺保存在4℃低钾右旋糖苷液中4h;无心跳供体-缺血30min组供体放血处死后,维持通气30min,使供肺在热缺血30min后冷保存;无心跳供体-缺血60min组方法同无心跳供体-缺血30min组,不同之处在于供肺热缺血60min。各组大鼠循环回路连接后,于1,15,30,45,60min测出气道峰压和肺静脉血氧气分压。灌注结束后检测供肺湿质量干质量比和丙二醛水平。结果与结论:有心跳供体组和无心跳供体-缺血30min组所有指标比较差异均无显著性意义(P>0.05)。各组气道峰压随时间的延长逐渐升高,但无心跳供体-缺血60min组升高程度高于有心跳供体组和无心跳供体-缺血30min组(P<0.05)。各组供肺血氧气分压均随着时间的延长而降低,无心跳供体-缺血60min组供肺血氧气分压低于有心跳供体组和无心跳供体-缺血30min组(P<0.05)。无心跳供体-缺血60min组供肺湿质量干质量比和丙二醛水平较有心跳供体组和无心跳供体-缺血30min组高(P<0.05)。结果提示大鼠无心跳供肺热缺血30min肺移植灌注模型是一种安全有效的肺移植方法。     

骨髓间充质干细胞移植对家兔急性肺损伤的保护作用

背景:急性呼吸窘迫综合征重要病理改变是肺泡一毛细血管膜屏障的损伤,以及所导致肺泡渗出液中富含蛋白质的肺水肿.骨髓间充质干细胞能够继续分化和不断自我更新,并最终分化为多种类型细胞,这有可能为治疗肺损伤提供一个新的途径.目的:探讨骨髓间充质干细胞移植对内毒素诱发急性肺损伤模型兔的保护作用.设计、时间及地点:随机对照动物实验,于2007-10/2008-01在唐都医院中心实验室完成.材料:家兔20只,2只用于制备骨髓间充质干细胞,剩余18只随机分为3组:盐水对照组、肺损伤模型组、细胞移植组,6只,组.内毒素为Sigma公司产品.方法:Ficoll法分离培养兔骨髓间充质干细胞,传至第3代备用.肺损伤模型组、细胞移植组兔通过向气管内滴注内毒素建立急性肺损伤,急性呼吸窘迫综合征模型,造模成功30 min后,细胞移植组经右侧颈静脉注入骨髓间充质干细胞悬浮液2 mL(细胞数1×105),盐水对照组、肺损伤模型组同法给予等量生理盐水.主要观察指标:支气管肺泡灌洗液中性粒细胞数日、肺组织湿干比及蛋白含量,肺组织病理变化.结果:湿十比值升高提示肺水肿的存在,中性粒细胞数量增加提示较重的炎性反应存在,蛋白含量升高提示肺泡一毛细血管内膜屏障受损.移植48 h后与盐水对照组比较,肺损伤模型组支气管肺泡灌洗液中性粒细胞数目、蛋白含量均明显降低(P<0.01),湿干比明显升高(P<0.01);与肺损伤模型组比较,细胞移植组支气管肺泡灌洗液中性粒细胞数目、蛋白含量均明显升高(P<0.01),湿干比明显降低(P<0.01).苏木精一伊红染色结果显示,盐水对照组肺泡组织结构正常,肺损伤模型组肺组织出现典型的急性肺损伤改变,细胞移植组肺组织病理变化较轻.结论:利用骨髓间充质干细胞移植可显著减轻内毒素诱导的急性肺损伤.     

Bleomycin-induced acute lung injury in the rat does not influence pulmonary vascular responsiveness in vitro.

OBJECTIVE: To investigate the effects of the intratracheal and iv administration of bleomycin on the contraction and endothelially dependent vasodilation of rat pulmonary arteries in vitro. DESIGN: Prospective pharmacologic study. SETTING: National Heart and Lung Institute, London, UK. INTERVENTIONS: Intratracheal saline, intratracheal and iv bleomycin. MEASUREMENTS AND MAIN RESULTS: Rats treated with intratracheal bleomycin developed a significant increase in mean lung wet/dry weight ratio (5.6 +/- 0.4 [SEM] vs. 3.9 +/- 0.1, p less than .05) when compared with saline-treated control animals, confirming the development of pulmonary edema. However, these rats displayed normal relaxant responses to the endothelially dependent vasodilator acetylcholine and a normal contractile response to phenylephrine in vitro. Intravenous bleomycin had no effect on either wet/dry weight ratio or the response to either drug. CONCLUSIONS: Despite evidence for the loss of endothelial integrity that characterizes lung injury after intratracheal bleomycin, isolated pulmonary artery rings in vitro showed no loss of endothelial cell function. The role of the endothelium in modulating pulmonary ventilation/perfusion matching after lung injury is unclear.     

Salutary effects of prostaglandin E1 in perfused rat lungs injured with hydrogen peroxide

Studies were conducted in isolated, buffer-perfused rat lungs to determine if prostaglandin (PG) E1 attenuated pulmonary edema provoked by hydrogen peroxide (H2O2). When lungs were challenged by 60 min of perfusion with H2O2 (generated by the reaction between glucose and glucose oxidase) the wet weight-to-dry weight ratio increased from control by 54%, indicating development of pulmonary edema. In contrast, lungs treated simultaneously with H2O2 plus PGE1 (1 microgram/min) failed to exhibit an elevated wet-to-dry weight ratio. H2O2-injured lungs demonstrated a modest 2 torr increase in pulmonary arterial perfusion pressure that was not influenced by simultaneous treatment with PGE1. Both radioimmunoassay (RIA) and high-performance liquid chromatographic (HPLC) analysis detected increased amounts of (5S)-5-hydroxy-6,8,11,14 eicosatetraenoic acid in the perfusion medium of H2O2-injured lungs (RIA, 48.0 +/- 14.7; HPLC, 54.8 +/- 13.5) relative to controls (RIA, 6.6 +/- 1.6; HPLC, 6.8 +/- 1.9), and simultaneous treatment with PGE1 tended to blunt this increase (RIA, 29.2 +/- 8.3; HPLC, 29.8 +/- 7.6). PGE1 abolished the increase in wet weight-to-dry weight ratio induced by exogenous leukotriene C4. Production of H2O2 by the glucose-glucose oxidase reaction was not influenced by PGE1. Taken together, these observations indicate that PGE1 attenuates H2O2-induced pulmonary edema formation in buffer-perfused rat lungs by mechanisms that may relate to inhibition of lung 5'-lipoxygenase activation and/or to inhibition of the injurious effects of endogenously produced lipoxygenase products.     

Evidence for lipid peroxidation by paraquat in the perfused rat lung

In order to evaluate the effect of paraquat on oxidative radical reactions in the lung, we studied MDA production and chemiluminescence (spontaneous and tBuOOH-induced) in the isolated rat lung. After 2 hr of perfusion with 3.0 mM paraquat, MDA content in lung homogenates was 16 +/- 7 nmol/gm dry weight higher than in control lungs (mean +/- S.E., n = 7, p less than 0.05 by paired test); during 30 min of perfusion, malondialdehyde efflux was 33 +/- 15 nmol/gm dry weight higher than in control perfusates (n = 6, p less than 0.05). Spontaneous chemiluminescence was not augmented by 2 hr of perfusion with concentrations of paraquat ranging from 0.75 to 6.0 mM. On the other hand, tBuOOH-induced chemiluminescence was 17% +/- 3 higher immediately after the addition of hydroperoxide and reached a 16% +/- 6 higher plateau for the paraquat-perfused lungs than for control lungs (n = 10, p less than 0.05). Spectral analysis of the light emitted during induced chemiluminescence demonstrated peak intensity between 630 and 730 nm for both control and paraquat-treated lungs. Increased MDA production and increased induced chemiluminescence indicate that perfusion with paraquat enhances lipid peroxidation in the isolated rat lung.     

Effects of partial liquid ventilation on regional pulmonary blood flow distribution of isolated rabbit lungs

OBJECTIVE: Partial liquid ventilation with perfluorocarbons may increase alveolar hydrostatic transmural pressure and may result in a redistribution of pulmonary blood flow from dependent to nondependent lung regions. To test this hypothesis under controlled study conditions, we determined intrapulmonary blood flow distributions during gas and perfluorocarbon ventilation in isolated rabbit lungs. DESIGN: Controlled animal study with an ex vivo isolated lung preparation. SETTING: Research laboratory for Experimental Anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: The lungs were perfused with autologous blood at constant flow (150 mL/min) and ventilated with 5% C(O2) in air (positive end-expiratory pressure, 2 cm H2O; tidal volume, 10 mL/kg body weight; respiratory rate, 30 breaths/ min) without and with perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Regional lung perfusion was measured with colored microspheres in apical, central, peripheral, and basal samples before and after bronchial instillation of perfluorocarbons. Compared with gas ventilation, intrapulmonary blood flow during perfluorocarbon ventilation was higher in apical samples (49.4+/-8.6 mL/min/g vs. 38.3+/-6.8 mL/min/g dry weight; p = .03) and lower in basal samples (22.2+/-5.1 mL/min/g vs. 39.9+/-8.2 mL/min/g; p = .04). CONCLUSIONS: Our findings suggest that during partial liquid ventilation, intrapulmonary blood flow is redistributed toward less-dependent lung regions. (Crit Care Med 2000; 28:1522-1525) KEY WORDS: partial liquid ventilation; perfluorocarbons; isolated rabbit lungs; pulmonary circulation; regional blood-flow distribution; colored microspheres     

Prevention of ischemia reperfusion injury by positive pulmonary venous pressure in isolated rat lung

Pulmonary ischemia-reperfusion (I/R) without tissue hypoxia induces inflammatory cytokine mRNA expression in the lung under the condition of 0 mm Hg pulmonary venous pressure (0PVP), which might be a cause of I/R injury. Our aim is to determine whether the pulmonary vascular endothelium expresses cytokine mRNAs and their corresponding proteins or develops I/R injury when positive PVP is maintained during ischemia to provide a positive stretch to the endothelium throughout the ischemic period. In isolated, perfused, and ventilated rat lungs, the right and left pulmonary arteries were isolated, and the left lung was selectively occluded for 60 min and then reperfused for 30 min. During ischemia, the left atrial pressure was maintained at 5 mm Hg (5PVP) or 0PVP. TNF-alpha, IL-1beta, IL-6, and IL-10 mRNA expression in the lungs was evaluated by RT-PCR and in situ hybridization, and the production and localization of corresponding proteins were determined by staining with fluorescence-labeled antibodies against the cytokines and an antibody against CD34. Pulmonary vascular/epithelial permeability was evaluated by measuring albumin content in bronchoalveolar lavage (BAL) fluid and wet/dry ratio. At 5PVP, there were no increases in the left lung perfusion pressure, albumin content in BAL fluid, wet/dry ratio, or expression of cytokine mRNAs and their corresponding proteins on the vascular endothelium by I/R. In contrast, at 0PVP, the increased expression of cytokine mRNAs and their corresponding proteins on the vascular endothelium by I/R was verified. The finding that the application of 5PVP during ischemia abolished the expression of cytokine mRNAs and their corresponding proteins as well as the I/R injury gives us new insights in the study of lung preservation for transplantation.     

Intestinal circulation, oxygenation and metabolism is not affected by oleic acid lung injury

This study was performed to establish a platform for further studies on effects of ventilatory treatment modalities on the intestines during mechanical ventilation of acute lung injury (ALI). We tested the hypotheses that oleic acid (OA) infusion causes changes in intestinal circulation, oxygenation and metabolism, and that OA is distributed to tissues outside the lung. This was performed as an experimental, prospective and controlled study in an university animal research laboratory. Thirteen juvenile anaesthetized pigs were used in the main study, where seven were given an intravenous infusion of 0.1 ml kg(-1) OA and six served as control (surgery only). In a separate study, four animals were given an intravenous infusion of 0.1 ml kg(-1) (3)H-labelled OA. We measured systemic and mesenteric (portal venous blood flow, jejunal mucosal perfusion) haemodynamic parameters, mesenteric oxygenation (jejunal tissue oxygen tension) and systemic cytokines (tumour necrosis factor-alpha and interleukin-6). We calculated mesenteric lactate flux and mesenteric oxygen delivery, uptake and extraction ratio. In the animals given 3H-OA, we measured 3H-OA in different tissues (lungs, heart, liver, kidney, stomach, jejunum, colon and arterial blood). We found that OA given intravenously is distributed in small amounts to the intestines. This intestinal exposure to OA does not cause intestinal injury when evaluating mesenteric blood flow, metabolism or oxygenation. OA infusion induced a moderate increase in mean pulmonary arterial pressure and a decrease in PaO2/Fraction inspired O2 (P/F) ratio, giving evidence of severe lung injury. Consequently, the OA lung injury model is suitable for studies on intestinal effects of ventilatory treatment modalities during mechanical ventilation of ALI.