卡托普利在肺保存中的作用

目的 研究卡托普利在肺保存中的作用及可能的作用机制。方法 将猪分为2组，对照组用4℃改良的Euro-Colling液（E－C液）对供肺进行灌洗和保存，实验组用4℃含卡托普利（500μmol/L)的E－C液对供肺进行灌洗和保存，然后进行左肺移植。在再灌注后0．5、1和2h采血及肺组织，测定血氧分压、肺血管阻力、NO2^-/NO3^－含量、超氧化物歧化酶（SOD）的活性以及脂质过氧化产物丙二醛（MDA）的含量。结果 实验组的左肺氧合功能明显好于对照组，肺循环阻力及肺含水量也较对照组相应时间低，差异均有显著性；实验组在此期间的NO2^-/NO3^-含量较对照组有明显高（P＜0．01），但肺组织中的SOD活性及MDA含量变化不大。结论 卡托普利对供肺有较好的保护作用，能降低移植后肺循环阻力及肺含水量，对NO升高有一定作用，但对氧自由基的形成及消除效果不理想。     

左旋精氨酸对离体兔肺脏保存质量的影响

目的　观察左旋精氨酸（ＬＡｒｇｉｎｉｎｅ,ＬＡｒｇ） 对离体兔肺脏保存的保护作用。　方法　３０ 只健康家兔随机分成对照组和左旋精氨酸组（ＬＡｒｇ 组） ,每组１５ 只,对照组兔肺脏给予Ｅｕｒｏｃｏｌｌｉｎｓ 液进行灌注,ＬＡｒｇ 组给予含ＬＡｒｇ的Ｅｕｒｏｃｏｌｌｉｎｓ 液进行灌注,灌注总量６０ｍｌ／ｋｇ ,灌注压力１ ．９６ｋＰａ（２０ｃｍ Ｈ２ Ｏ） ,灌注完毕整取下心肺组织浸入４ ℃保存液中冷藏,７ 小时后取肺进行离体复灌,测定肺血管阻力、血气分析、肺血管对乙酰胆碱舒血管反应性、肺组织湿／ 干重比例及肺组织电子显微镜检查等指标。　结果　对照组肺血管阻力、肺组织湿／ 干重比例均高于ＬＡｒｇ 组（ Ｐ＜ ０ ．０５） ,肺血管对乙酰胆碱反应性对照组较ＬＡｒｇ 组差, 血气分析肺静脉血氧分压对照组下降明显（ Ｐ ＜ ０－０１） ,ＬＡｒｇ 组肺组织形态轻微改变,而对照组肺组织水肿明显、渗出严重。　结论　ＬＡｒｇ具有改善离体兔肺脏的保存效果。     

改良SDMC-2液对离体犬肺保存-移植的研究

目的在山东医科大学心脏液2号（SDMC-2）的基础上，开发有利于肺保存的器官保存液。方法30条Beagle犬随机分为3组，每组供、受体各5条，供体左肺经3种保存液于4℃保存12h；然后行受体左肺移植，测定并比较再灌注后的平均肺动脉压力（MPAP）及动脉血氧分压（PaO2）；对保存末及再灌注后肺组织标本进行电镜观察。结果（1）保存-移植再灌注后，3组与正常对照组比较：MPAP升高，PaO2降低（P〈0．01）；超微结构均不同程度损伤。（2）改良SDMC-2液保存组再灌注后即刻、0．5、1h的MPAP无明显变化，均低于相应时间的低钾保存液（LPD液）、SDMC-2液保存组（P〈0．05）；PaO2则高于相应时间的LPD液、SDMC-2液保存组（P〈0．05）。电镜显示：改良SDMC-2液保存组肺组织超微结构损伤最轻。结论改良SDMC-2液具有优良的保存效果及抗再灌注损伤能力。     

控制性再灌注防止肺再灌注损伤的研究

目的　探讨控制性再灌注在预防肺缺血再灌注 (I/R)损伤中的作用及其机制。方法将猪分为 2组 ,10只猪切取左肺作供体 ,4℃改良的E C液灌洗和保存 ,4h后进行左肺移植。对照组常规操作 ,实验组采用控制性再灌注 :灌注液 (去白细胞血 :改良Buckberg液 =4∶1) ;灌注压 2 0mmHg ;灌注时间 10min。 0 .5、1和 2h后测血氧分压、肺血管阻力、肺顺应性、一氧化氮 (NO)含量、丙二醛 (MDA)含量、肺干 /湿重比。结果　实验组的左肺氧合功能 ,肺顺应性明显好于对照组 ,肺循环阻力、MDA值及肺含水量均低于对照组 (P <0 .0 1) ;实验组肺中NO含量较对照组明显升高 (P <0 .0 1)。结论　控制性再灌注能明显降低肺I/R损伤 ,起到了较好的移植肺保护效果。     

L-精氨酸对大鼠胰腺移植缺血再灌注损伤的保护作用及其机制

目的探讨L-精氨酸（L-Arginine，L-Arg）对大鼠胰腺移植缺血再灌注（I／R）损伤的影响及其机制。方法SD大鼠作为供、受体行胰腺移植术，给予不同方式处理：假手术组（Sham）：只行开腹术；对照组（Control）：只行胰腺移植术，不行预处理；缺血预处理组（IPC）：在供胰切取前阻断血供10min，然后再灌注10min；L-精氨酸组（L-Arg）：行胰腺移植术，再灌注前先经下腔静脉注射L-Arg 10mg／kg体重；L-硝基精氨酸甲酯组（L-NAME）：供胰切取时阻断血供10min，再灌注10min；然后行移植术，在再灌注前，先经下腔静脉缓慢注射L-NAME 10mg／kg体重。各组手术完成后，于再灌注6h检测血清淀粉酶、肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）水平，胰腺细胞凋亡指数、胰腺细胞bcl-2蛋白表达情况和胰腺组织病理改变。结果L-Arg和IPC都降低TNF-α水平（P〈0．01）和细胞凋亡水平（P〈0．01），NO水平升高（P〈0．01）。而L-NAME可阻断该保护效应。IPC和L-Arg均能激活bcl-2蛋白的表达。结论L-Arg可以模拟IPC对大鼠胰腺移植I／R损伤的保护作用，其机制与合成NO，激活bcl-2基因的表达有关。     

左旋精氨酸对离体免肺脏保存质量的影响

目的 观察左旋精氨酸（Ｌ－Ａｇｉｎｉｎｅ,Ｌ－Ａｒｇ）对离体兔肺脏保存的保护作用。方法 ３０只健康家兔随机分成对照组和左旋精氨酸组（Ｌ－Ａｒｇ组）,每组１５只,对组兔肺脏给予Ｅｕｒｏ－ｃｏｌｌｉｎｅｓ液进行灌注,Ｌ－Ａｒｇ组给予含Ｌ－Ａｒｇ的Ｅｕｒｏ－ｃｏｌｌｉｎｓ液进行灌注,灌注总量６０ｍｌ／ｋｇ,灌注压力１．９６ｋＰａ（２０ｃｍＨ２Ｏ）,灌注完毕整取心肺组织浸入４℃保存液中冷藏,７小时后取肺地     

高胸段硬膜外阻滞对猪急性心肌缺血/再灌注损伤的保护作用

目的：探讨高胸段硬膜外阻滞（HTEA）对心肌缺血／再灌注损伤的保护作用。方法：20只家猪随机分为两组，结扎左冠状动脉前降支（LAD）造成造血40min后再灌注6h，实验组（n=10)结扎前硬膜外腔注入0．5％布比卡因2ml;对照组（n=10)结扎前硬膜外腔注入生理盐水2ml。测定心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）、血浆超氧化物歧化酶（SOD）活性、血清丙二醛（MDA）浓度、心肌乳酸（LA）释放量。结果：（1）实验组硬膜外阻滞的HR减慢22％，MAP、CVP分别降低25％和28％，而对照组血液动力学无明显变化。（2）实验组SOD活性变化不显著，再灌注5h、6h活性升高（P＜0．01）；MDA浓度在4h降至最低点（P＜0．05）；对照组SOD活性明显降低（P＜0．05），MDA含量明显增加（P＜0．05）。（3）两组心肌LA释放量在开放前达到高峰，之后随着供血、供氧的恢复逐渐下降，但实验组明显低于对照组（P＜0．01）。（4）开始再灌注时由于发生室颤实验组死亡1只，对照组死亡只（P＜0．05）。结论：HTEA可以减轻心肌缺血／再灌注损伤，其机制与保护SOD活性，降低心肌氧耗及脂质过氧化程度有关。     

大鼠肝脏缺血再灌注及低温保存过程中氧自由基变化的实验研究

目的　观察大鼠肝脏缺血再灌注及低温保存过程中氧自由基的变化。方法　建立大鼠肝脏假手术、热缺血再灌注和原位肝移植模型 ,分别测定再灌注 1h和移植术后 2h下腔静脉血中超氧化物歧化酶 (SOD)、乳酸脱氢酶 (LDH)和血清中脂质过氧化物酶 (LPO)的变化 ,并进行组织学观察。结果　术前 30min静脉注射别嘌醇或灌洗液及保存液中加别嘌醇的实验组大鼠 ,其全血中SOD的活力高于条件相同、但不给予别嘌醇的对照组 ,LPO及LDH的含量低于对照组 ,其各项测定值与假手术组比较 ,差异不显著 ;实验组和假手术组的大鼠肝组织病理改变均轻于对照组。结论　大鼠肝脏缺血再灌注及低温保存过程中氧自由基明显增加 ,并且造成肝脏的损害     

超氧化物歧化酶对大鼠肝脏缺血再灌注损伤保护作用的体外实验

目的：探讨氧自由基清除剂对大鼠肝脏缺血再灌注损伤的保护作用及其机理。方法：将Wistar大鼠分成三组，各组通过门静脉插管，对肝脏进行原位灌洗，心脏搏动组以4℃HTK液灌洗；心脏停跳组在心脏搏动停止60min后，以同样方法灌洗肝脏；SOD实验组灌洗方法同心脏停跳组，但灌洗液中含有超氧化物歧化酶（SOD）7500IU。灌注结束后，快速切取肝脏，于4℃HTK液中保存24h，然后在体外以Krebs-Henseleit缓冲液再灌注45min。测定再灌注过程中的门静脉压力，收集再灌注液，进行血气分析，测定其中丙氨酸转氨酶（ALT）、谷氨酸乳酸脱氢酶（GLDH）及脂质过氧化物（LPO）的含量；切取肝组织，检测其能量底物总和（TAN）及细胞凋亡情况。结果：再灌注期间，SOD实验组的门静脉压力为（6．4±0．9）cmH20，明显低于心脏停跳组的（12．1±0．7）cmH20（P〈0．01）。随着再灌注时间的延长，灌注液中AL]r和GLDH的浓度不断升高，但SOD实验组明显低于心脏停跳组（P〈0．05）。心脏停跳组肝脏氧消耗量明显低于心脏搏动组（P〈0．01），而SOD实验组氧消耗量明显增加（P〈0．01）。SOD实验组的TAN为（7．6±0．4）μmol／g，明显高于心脏停跳组的（5．3±0．7）,μmol／g（P＜0．05）。SOD实验组灌注液中LPO的含量为（0．42±0．10）nmol／g，明显低于心脏停跳组的（0．98±0．18）nmol／g（P＜0．01）。心脏搏动组只有极少量的肝窦内皮细胞和肝细胞凋亡，SOD实验组中凋亡细胞的数量也非常有限，而在心脏停跳组，则有大量的肝窦内皮细胞发生凋亡。结论：在体外，SOD能显著减轻大鼠肝脏的缺血再灌注损伤，这可能与SOD抑制了氧自由基所致的细胞凋亡有关。     

抑肽酶-低钾-右旋糖酐保存液对兔肺缺血再灌注损伤的影响

目的探讨抑肽酶-低钾-右旋糖酐保存液对常温兔肺缺血再灌注损伤的影响。方法成年新西兰大白兔18只,体重0．9～1．5kg,雌雄不拘,随机分为3组（n=6）：对照组（C组）、低钾-右旋糖酐（LPD）组（L组）、抑肽酶＋LPD组（A组）。C组直接阻断左肺门,不灌注肺保存液,L组和A组阻断左肺动脉,待肺膨胀后分别经左肺动脉导管灌注LPD保存液或抑肽酶＋LPD保存液30ml/kg（含抑肽酶150kIU/ml）,灌注结束后阻断左肺静脉,在肺膨胀一半时阻断左主支气管,2h后依次开放左肺静脉、动脉和左主支气管,再灌注90min后处死动物取出左肺,测定肺组织丙二醛（MDA）含量及髓过氧化物酶（MPO）活性,计算肺组织干湿重比（D/W）,观察肺组织病理学变化；分别于缺血前及再灌注15、60、90min检测动脉血氧分压（PaO2）及血清肿瘤坏死因子-α（TNF-α）浓度。结果与缺血前比较,3组再灌注期间血清TNF-α浓度升高,PaO2下降（P＜0．01）；与C组比较,L组、A组再灌注期间肺组织MDA含量、MPO活性降低,D/W升高,血清TNF-α浓度降低,PaO2升高（P＜0．05或0．01）；与L组比较,A组肺组织MDA含量、MPO活性降低,D/W升高,血清TNF-α浓度降低,PaO2升高（P＜0．01）。A组肺组织水肿、渗出、损伤等病理变化较C组和L组减轻。结论抑肽酶-LPD保存液可减轻兔常温肺缺血再灌注损伤,改善肺功能。     

Influence of intraalveolar oxygen concentration on lung preservation in a rabbit model

We previously reported the use of an inexpensive screening model for lung preservation involving ventilation and perfusion of excised rabbit lungs after their preservation. We now have extended this model by perfusing the preserved lung in cross circulation with an anesthetized rabbit to permit stable reperfusion of the preserved lungs for 60 minutes. With this model we compared the results of lung preservation with the lungs inflated with nitrogen, room air, or 100% oxygen during 24 hours of hypothermic storage. Four groups of animals were studied: group 1, excision and immediate evaluation; group 2, inflation with room air and storage for 24 hours at 10 degrees C; group 3, same as group 2, with 100% oxygen for inflation during storage; group 4, same as group 2, with 100% nitrogen for inflation during storage. Assessment of the ex vivo perfused lung consisted of (1) blood gas analysis of inflow and outflow blood at 10-minute intervals; (2) continuous pulmonary artery and airway pressure monitoring; (3) measurement of pulmonary venous oxygen tension after 1 hour of reperfusion, with inflow oxygen tension adjusted to 15 mm Hg; (4) wet/dry weight ratio. We conclude that the paracorporeal circuit does not, in itself, cause lung injury over a 1-hour period; lungs preserved with nitrogen inflation rapidly became edematous and failed to function on reperfusion. Preservation with 100% oxygen inflation appears superior to inflation with room air.     

Intracellular-type solution flush for preservation of myocardium and coronary and pulmonary artery flow surface

Modified Euro-Collins solution (ECS), which has been successfully used in kidney, liver and lung transplantation, was tested concerning myocardial and endothelial preservation in nine piglets. In six (group I), 1-hour cardiac arrest was induced with cold modified ECS, and in three (group II) heart-lung transplantation was performed, using modified ECS for graft preservation. In group I myocardial energy preservation was determined with biochemical assays for adenosine triphosphate, creatine phosphate, lactate and creatine 5, 15, 30 and 60 minutes after aortic clamping, and preservation of endothelium in the aorta and coronary arteries was studied with scanning electron microscopy. In group II electron microscopy was performed on endothelial samples from the ascending aorta and coronary and pulmonary arteries of the heart-lung block after excision, after 2 hours of ischemia, and after 1-2 hours of reperfusion. High-energy phosphates decreased progressively during the ECS cardioplegia in group I, and circulatory support was required during the post-transplantation reperfusion period in group II. The endothelial lining in all specimens was remarkably well preserved, however. Modified ECS flush thus was ideal for vascular endothelium but, because of its poor energy-preserving capacity, unsuitable for cardioplegia.     

Endothelium-dependent relaxation of canine pulmonary artery after prolonged lung graft preservation in University of Wisconsin solution: role of L-arginine supplementation.

BACKGROUND: The University of Wisconsin (UW) solution has been demonstrated to enhance pulmonary allograft preservation. Endothelial nitric oxide (NO) production has been shown to be significantly impaired after ischemia and reperfusion (I/R) injury. The present experiments aimed to determine the protective effects of pulmonary endothelium-dependent function by using supplemental NO in University of Wisconsin (UW) solution following prolonged lung graft preservation. METHODS: Thirty-six healthy mongrel dogs underwent thoracotomy to expose the left lung. In addition to a group given UW solution (n = 4), 100 micromol/liter l-arginine, (n = 7), 100 micromol/liter N(G)-monomethyl-l-arginine (l-NMMA n = 7) and 1.0 micromol/liter 3-morpholinosydnonimine (SIN-1, n = 18 respectively, were added to UW solution, and infused from the aortic root and pulmonary artery to the pulmonary vein. The perfused lung was then allowed to inflate to its maximum volume for 24-hour oxygenated preservation in each supplemented condition of UW solution at 4 degrees C. In the SIN-1 group, the preservation period was further divided into 8 hours and 16 hours, respectively. Rings of the third-order pulmonary artery of the inflated lung were then suspended in organ chambers to measure isometric force. RESULTS: Endothelium-dependent relaxation (EDR) to acetylcholine, adenosine diphosphate and sodium fluoride of the pulmonary rings in the l-arginine group was significantly preserved compared with UW-solution-only group. The l-NMMA group showed significant EDR impairment after 24-hour preservation compared with the UW solution group. Similar to the l-arginine group, the SIN-1 group showed significant EDR protection with 8-hour preservation, but not with 24-hour preservation. In contrast, EDR to calcium ionophore A23187 showed no EDR changes after 24-hour preservation in any of the supplemented groups. CONCLUSIONS: Supplemental l-arginine in UW solution ameliorates impaired pulmonary EDR following prolonged lung preservation of up to 24 hours.     

Protective effects of inhaled nitric oxide and gabexate mesilate in lung reperfusion injury after transplantation from non-heart-beat donors.

BACKGROUND: The use of lung grafts from non-heart-beat donors (NHBDs) is one way of solving the critical donor organ shortage. Inhaled nitric oxide (NO) and gabexate mesilate (FOY), a protease inhibitor, can attenuate some types of neutrophil-mediated tissue injury. Using an isolated lung ventilation and perfusion model, we studied the effects of these agents on reperfusion injury following lung transplantation from NHBDs. METHODS: Five groups of minipigs were studied. In group 1(n = 6), the lungs were flushed and harvested after cardiac arrest, and were reperfused for 2 hours after 2 hours of cold ischemia. In group 2 (n = 6), the lungs were harvested after 2 hours of in situ warm ischemia, followed by 2 hours of cold ischemia and 2 hours of reperfusion. In groups 3 (n = 7), 4 (n = 7), and 5 (n = 6), the procedure was the same as in group 2, except in group 3, NO was inhaled before and after ischemia, in group 4, FOY was given intravenously, and in group 5, a combination of inhaled NO and intravenous FOY were administered. RESULTS: Compared with group 1, group 2 had higher mean pulmonary arterial pressure, vascular resistance, and lower arterial blood oxygen tension. Furthermore, these negative effects of warm ischemia were also reflected in the contents of bronchoalveolar lavage fluid, tissue myeloperoxidase (MPO) activity, histology, and permeability change. Either FOY or NO administration (groups 3 or 4) ameliorated the associated injury. A combination of FOY and NO use (group5) decreased the parameters of lung reperfusion injury measurement to a larger degree than either agent individually. CONCLUSIONS: The inhaled NO and FOY can protect NHBD lung grafts at an early reperfusion period. Their use in combination has an additive protective effect that might be applied to the protection of NHBD grafts from preservation and reperfusion injury.     

Reliable 18-hour lung preservation with University of Wisconsin solution

Objectives: A common experimental model is necessary to assess therapeutic intervention in lung preservation. This study was designed to establish lung preservation in an ex vivo rat model that would enable post-storage lung function to be stably evaluated during the 2 hours following reperfusion.Subjects and Methods: Lungs isolated from Sprague-Dawley rats (n=36) were flushed and stored in University of Wisconsin solution at 4°C for the following periods: Group 1: no storage (n=12); Group 2: 4 hours (n=8); Group 3: 18 hours (n=8); and Group 4: 24 hours (n=8). After storage in University of Wisconsin solution, all lungs were reperfused with homologous venous blood exsanguinated from donor rats using a pulsatile perfusion system. Pulmonary variables, including lung airway resistance, dynamic lung compliance, total pulmonary vascular resistance, and blood gas analysis, were assessed during reperfusion.Results: All lungs stored for 24 hours failed within 1 hour of reperfusion. Lungs stored for up to 18 hours survived 2-hour reperfusion. pO₂ in groups 1 to 3 (87.1 ± 3.5, 89.7 ± 2.4, and 80.6 ± 6.4, pO₂ mmHg at 30 minutes) was similar during reperfusion, but that in group 4 (49.5 ± 4.6 mmHg, at 30 minutes) deteriorated within 30 minutes after reperfusion onset. Lung airway resistance, dynamic lung compliance, and shunt fraction also deteriorated in group 4, whereas these variables were similar in groups 1, 2, and 3 during reperfusion.Conclusions: These results indicate that this experimental model provided a reliable evaluation of preserved lung function after 18-hour cold storage. Any therapeutic intervention for extending storage periods or ameliorating poststorage lung function is easily tested using this system.     

Reliable 18-hour lung preservation with University of Wisconsin solution An ex vivo rat model with a pulsatile perfusion system

Objectives: A common experimental model is necessary to assess therapeutic intervention in lung preservation. This study was designed to establish lung preservation in an ex vivo rat model that would enable post-storage lung function to be stably evaluated during the 2 hours following reperfusion.Subjects and Methods: Lungs isolated from Sprague-Dawley rats (n=36) were flushed and stored in University of Wisconsin solution at 4°C for the following periods: Group 1: no storage (n=12); Group 2: 4 hours (n=8); Group 3: 18 hours (n=8); and Group 4: 24 hours (n=8). After storage in University of Wisconsin solution, all lungs were reperfused with homologous venous blood exsanguinated from donor rats using a pulsatile perfusion system. Pulmonary variables, including lung airway resistance, dynamic lung compliance, total pulmonary vascular resistance, and blood gas analysis, were assessed during reperfusion.Results: All lungs stored for 24 hours failed within 1 hour of reperfusion. Lungs stored for up to 18 hours survived 2-hour reperfusion. pO₂ in groups 1 to 3 (87.1 ± 3.5, 89.7 ± 2.4, and 80.6 ± 6.4, pO₂ mmHg at 30 minutes) was similar during reperfusion, but that in group 4 (49.5 ± 4.6 mmHg, at 30 minutes) deteriorated within 30 minutes after reperfusion onset. Lung airway resistance, dynamic lung compliance, and shunt fraction also deteriorated in group 4, whereas these variables were similar in groups 1, 2, and 3 during reperfusion.Conclusions: These results indicate that this experimental model provided a reliable evaluation of preserved lung function after 18-hour cold storage. Any therapeutic intervention for extending storage periods or ameliorating poststorage lung function is easily tested using this system.     

The nitric oxide synthase cofactor tetrahydrobiopterin reduces allograft ischemia-reperfusion injury after lung transplantation.

OBJECTIVE: Exogenous nitric oxide reduces ischemia-reperfusion injury after solid organ transplantation. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthases, may restore impaired endothelium-dependent nitric oxide synthesis. We evaluated whether tetrahydrobiopterin administration to the recipient attenuates lung reperfusion injury after transplantation in swine. METHODS: Unilateral left lung transplantation was performed in 15 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 L cold (1 degrees C) low-potassium-dextran solution and preserved for 20 hours. Group I animals served as controls. Group II and III animals were treated with a bolus of tetrahydrobiopterin (20 mg/kg). In addition, in group III a continuous infusion of tetrahydrobiopterin (10 mg/kg per hour over 5 hours) was given. One hour after reperfusion, the recipient right lung was occluded. Cyclic guanosine monophosphate levels were measured in the pulmonary venous and central venous blood. Extravascular lung water index, hemodynamic variables, lipid peroxidation, and neutrophil migration to the allograft were assessed. RESULTS: In group III a significant reduction of extravascular lung water was noted in comparison with the controls (P =.0047). Lipid peroxidation in lung allograft tissue was significantly reduced in group II (P =.0021) and group III ( P =. 0077) in comparison with group I. Pulmonary venous levels of cyclic guanosine monophosphate increased up to 23 +/- 1 pmol/mL at 5 hours in group II and up to 40 +/- 1 pmol/mL in group III (group I, 4.1 +/- 0.5 pmol/mL [I vs III]; P <.001), whereas central venous levels of cyclic guanosine monophosphate were unchanged in all groups. CONCLUSION: Tetrahydrobiopterin administration during lung allograft reperfusion may reduce posttransplantation lung edema and oxygen-derived free radical injury in the graft. This effect is mediated by local enhancement of the nitric oxide/cyclic guanosine monophosphate pathway.     

Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase

Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effects of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15 degrees C, stored in 4 degrees C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (PO2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial pO2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p less than 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p less than 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)     

内源性一氧化氮在非创伤性缺血预处理中对兔肺的保护作用

目的探讨内源性一氧化氮（NO）在非创伤性缺血预处理（N—WIP）中对兔肺缺血／再灌注（I／R）损伤的保护作用及可能机制。方法采用N-WIP及经典缺血预处理（C-IP）的动物模型，比较两种缺血预处理方法中内源性NO对兔肺在缺血／再灌注损伤中的保护效应。将40只大白兔随机平均分为4组：对照组、I／R组、C—IP组和NWIP组。对比观察各组血清及肺组织中NO2^-／NO3^-、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性以及肺湿／干重比。结果N—WIP组和C-IP组的兔肺再灌注后NO2^-／NO3^-含量均高于I／R组（P〈0．01），甚至高于对照组（P〈0．05）。两种缺血预处理组SOD活性均高于I／R组（P〈0．01），肺湿／干重比和MDA含量均低于I／R组（P〈0．05，P〈0．01）。结论N-WIP与C-IP对移植肺在缺血／再灌注损伤中具有同等强度的保护作用。其机制可能是通过诱发内源性一氧化氮（NO）舒张血管，从而起到保护血管内皮的效应。     

The superiority of an extracellular fluid solution over Euro-Collins' solution for pulmonary preservation.

Limited donor supply is the major factor restricting the application of lung transplantation. A uniformly reliable method of lung preservation would improve donor organ availability. At present, Euro-Collins' solution, an intracellular fluid-type solution, is most widely used in organ preservation. However, we have previously shown that initial pulmonary flush with an extracellular-type solution (low-potassium dextran solution [LPD]) provided better pulmonary preservation than Euro-C. In the present study, we used an in vitro-ventilated, blood-perfused rabbit lung model to examine whether the mechanism for this improvement was related to the effect of LPD during pulmonary flush or its effect during storage. Rabbit lungs were harvested and stored after pulmonary flush with different solutions (group 1: 400 ml of LPD; group 2: 400 ml of Euro-C; group 4: 300 ml of Euro-C followed by 100 ml of LPD; n = 5 in each group). The lungs were then preserved at 10 degrees C for 18 hr and reperfused with fresh venous blood. After 10 min of reperfusion, lungs in group 1 showed the highest PO2 (group 1: 124.4 +/- 7.7 mmHg; group 2: 46.2 +/- 9.4 mmHg P less than 0.01). Lungs in both group 3 and group 4 showed better lung function and lower wet/dry weight ratio than those in group 2. We conclude that LPD provides better lung preservation by its effects both on pulmonary flush and on storage.