前列腺素E1及硝酸甘油在离体脑保护中应用的实验研究

应用兔离体肺再灌注模型研究前列腺素Ｅ１（ＰＧＥ１）及硝酸甘油ＮＴＧ）在离体肺保护中的作用。１８只随机平均分为两组，对照组以ＬＰＤ液进行肺灌洗及保存，用药组以ＰＧＥ１１００μｇ．Ｌ＾－１及ＮＴＧ１０ｍｇ．Ｌ＾－１加入ＬＰＤ液中进行肺灌洗及保存。每组再分为三小组分别保存２、４、８小时后进行再灌注，测定再灌注后肺血管阻力（ＰＶＲ）、肺通所阻力ＬＲ，肺含水量及动脉发压以了解肺保护效果。结果示；用药组再灌注     

二种不同成份灌洗液保存效果的对比

目的 比较２种不同成份肺灌液的肺保存效果。方法 将犬分成２组,一组供肺采用改良的Ｅｕｒｏ－Ｃｏｌｌｉｎｓ液灌洗,另一组用低钾葡萄糖液（ＬＰＧ液,钾浓度４ｍｍｏｌ／Ｌ灌洗）,４℃保存６小时后行异体左肺移植,保留受体的右肺。术后１０分钟－７２小时定时阻断右肺动血液,采股动脉血作血液气体分析。并作病理检查。结果 改良的Ｅｕｒｏ－Ｃｏｌｌｉｎｓ液和ＬＰＧ液灌洗的肺移植后即刻受体动脉血氧分压（ＰａＯ２）分别     

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。     

BQ123对肺移植早期缺血再灌注损伤保护作用的实验研究

目的　研究内源性内皮素（ Ｅ Ｔ）１ 对肺移植早期缺血再灌注损伤的影响及 Ｅ Ｔ Ａ 受体阻断剂 Ｂ Ｑ１２３ 对其病理过程的保护作用。方法　以家犬（ 保存８ 小时） 左肺移植模型观察缺血再灌注。损伤过程中内源性 Ｅ Ｔ１ 产生及 Ｂ Ｑ１２３ 对其血流动力学、肺功能的作用。结果　 Ｂ Ｑ１２３ 组和对照组的平均动脉压、左房压、中心静脉压及组织形态学差异无显著性; Ｂ Ｑ１２３ 组平均肺动脉压、肺血管阻力指数及血清 Ｅ Ｔ１ 浓度明显低于对照组（ Ｐ ＜ ０ ．０１） ,心脏指数、动脉血氧分压明显高于对照组（ Ｐ ＜ ０ ．０１） ,而动脉二氧化碳分压明显低于对照组（ Ｐ ＜ ０ ．０１） ; Ｂ Ｑ１２３ 组肺组织含水百分比明显低于对照组（ Ｐ ＜０ ．０１） 。结论　 Ｂ Ｑ１２３ 对肺移植早期出现的缺血再灌注损伤具有保护作用。     

应用自体静脉做动脉重建时血管内皮细胞早期动态变化的研究

目的观察用自体静脉（ＡＶＧ）移植做动脉重建后，前列腺素１对血管内皮细胞（ＥＣ）早期变化的影响。方法４０只犬被分成两大组，根据重建动脉远端输出道良否，扩血管药物前列腺素１（ＰＧＥ１）投入与否再分成八小组。移植后ＡＶＧ标本通过处理，用图像分析系统，测定ＥＣ的脱落与覆盖面积。结果（１）被建动脉良好的输出道对移植后ＡＶＧ内ＥＣ再生与修复有明显促进作用，ＰＧＥ１的投入无此作用。（２）ＡＶＧ内瓣膜部位是移植后ＥＣ再生与修复的发源地。结论做血管移植时应尽量保护ＡＶＧ内瓣膜。     

一氧化氮供药减轻大鼠移植肝保存再灌注损伤

目的 研究一氧化氮供体药硝酸甘油（ＮＴＧ）对大鼠移植肝再灌注损伤的影响。方法 用０～４℃含或不含ＮＴＧ１０ｕｇ／ｍｌ的乳酸林格液灌洗及保存肝脏４ｈ后行原位肝移植，观察再灌注１０ｍｉｎ，２ｈ受体鼠血清氨基丙酸转氨酶（ＡＬＴ）、天冬氨酸转氨酶（ＡＳＴ）、乳酸脱氢酶（ＬＤＨ）；再灌注１ｈ，２ｈ的胆汁分泌量；再灌注２ｈ组织环到鸟苷（ｃＧＭＰ）含量；大于１ｄ和７ｄ的大鼠生存率。结果 再灌注１０ｍｉｎ血清ＡＳ     

前列腺素E1对先天性心脏病合并肺动脉高压的血流动力学效应

为了解前列腺素Ｅ１对先天性心脏病合并肺动脉高压的血流动力学效应，作者对３７例受试患者，在行右心导管（ＣＣ）检查中加用前列腺素Ｅ１（ＰＧＥ１）药物试验。ＰＧＥ１用量为每分钟１００～２００ｎｇ／ｋｇ，连续用药１５分钟。发现在低阻力组中（全肺阻力≤６０ｋＰａ·ｓ／Ｌ），ＰＧＥ１选择性扩张肺动脉作用明显；而高阻力组中（全肺阻力＞６０ｋＰａ·ｓ／Ｌ），ＰＧＥ１则对体循环影响较大。结果提示ＰＧＥ１用药剂量和用药效果与肺血管病变程度呈负效应。     

羊水肺泡表面活性物质和呼气末正压通气治疗呼吸窘迫综合征的实验研究

从人足月妊娠羊水提取肺泡表面活性物质（ＰＳ），用生理盐水反复灌洗豚鼠双肺复制急性呼吸窘迫综合征动物模型，观察气管内注入羊水ＰＳ与不同水平ＰＥＥＰ联合治疗的效果。结果：双肺灌洗导致严重的低氧血症和高碳酸血症；０．３９～０．５ｋＰａ的ＰＥＥＰ仅能轻度改善ＰａＯ２和ＰａＣＯ２；ＰＥＥＰ与１ｍｌ羊水ＰＳ（５０ｍｇ／ｍｌ）联合治疗显著改善ＰａＯ２和ＰａＣＯ２，其中０．７８～０．９８ｋＰａ的ＰＥＥＰ比０．３９～０．５９ｋＰａ的ＰＥＥＰ的效果更好；ＰＥＥＰ治疗可见肺泡不规则扩张，肺泡水肿明显，而ＰＳ与ＰＥＥＰ联合治疗未见明显肺实质损害。     

羊水肺泡表面活性物质和呼气末正压通气治疗呼吸窘迫综合征…

从人足月妊娠羊水提取肺泡表面活性物质，用生理盐水反复灌洗豚鼠双肺复制制急性呼吸窘迫综合征动物模型，观察气管内注入羊水ＰＳ与不同水平ＰＥＥ联合治疗的效果，结果：双肺灌洗导致严重的低氧血症和高碳酸血症；０．３９－０．５ｋＰａ的ＰＥＥＰ仅能轻度改善ＰａＯ２和ＰａＣＯ２；ＰＥＥＰ与１ｍｌ羊水ＰＳ（５０ｍｇ／ｍｌ）联合治疗显著改善ＰａＯ２和ＰａＣＯ２，其中０．７８－０．９８ｋＰａ的ＰＥＥＰ比０．３９－０．５     

重症急性胆管炎引发肺损伤时脂质过氧化作用的实验研究

动态检测兔重症急性胆管炎（ＡＣＳＴ）模型发病过程中肺组织脂质过氧化物（ＬＰＯ）和ＶｉｔＥ含量，结合肺功能和肺组织学的检测，发现发病６小时间肺组织ＶｉｔＥ明显下降（Ｐ〈０．０１），且随时间延长呈进行性下降；肺ＬＰＯ至１２小时时明显上升，２４小时时急剧上升，同时肺组织超微和显微结构出现类似成人呼吸窘迫综合征改变。血ＰＯ２至２４小时时方明显下降，而ＰＣＯ２明显上升。肺ＬＰＯ升高与肺ＶｉｔＥ呈负相关，与肺     

Celsior solution for improvement of currently used clinical standards of lung preservation in an ex vivo rat model.

OBJECTIVE: The introduction of Euro-Collins solution with its intracellular electrolyte composition has allowed for clinically accepted pulmonary preservation for up to 7 h of ischemic time. In recent years several alternative solutions have been developed for the improvement of pulmonary preservation. Celsior is an extracellular solution which has significantly reduced the ischemia/reperfusion (IR)-induced pulmonary damage in animal studies. So far, no larger experimental studies exist concerning the influence of Celsior on pulmonary gas exchange following IR. METHODS: In an extracorporeal rat lung model ten lungs, were each preserved with Celsior (CE) and Celsior/ prostacycline (CEPC, 6 mg/100 ml) at 4 degrees C and compared with preservation with low-potassium-Euro-Collins solution (LPEC, 40 mmol/l of potassium). After 2 h of ischemia the lungs were re-ventilated and reperfused using a roller-pump. Relative oxygenation capacity (ROC), pulmonary vascular resistance (PVR), peak inspiratory pressure (PIP) and wet/dry ratio were monitored for 50 min. Statistical analysis was performed using ANOVA. RESULTS: ROC was increased in all Celsior preserved organs compared with the EC group (P < 0.032). Though the CEPC group was found to have the lowest PIP and the least amount of lung water as assessed by wet/dry ratio, PVR was highest after 30-50 min. The significantly lowest PVR was determined in the CE group (P < 0.02). CONCLUSIONS: Celsior provides better lung preservation than LPEC solution, as demonstrated by a significantly increased oxygenation ability, a lower PVR and a decreased wet/ dry ratio. In vivo experiments and additional histological analysis are warranted for further evaluation of Celsior in lung preservation.     

Twenty-four-hour canine lung preservation using UW solution

The left lungs of 14 mongrel dogs were isolated, preserved, and then reperfused for 120 min. Three groups of lungs were investigated: group 1, nonpreserved lungs (control n = 5); group 2, lungs were flushed with UW solution and cold-stored (4-6 degrees C) in the same flush solution for 24 hr (n = 4); and group 3, lungs flushed and cold-stored with modified Euro-Collins' solution for 24 hr (n = 5). Airway pressure (AWP), static lung compliance (Cst), and pulmonary vascular resistance (PVR) 120 min after reperfusion were significantly higher in group 3 compared with the lungs in group 1 and group 2. AWP was 18.7 +/- 3.9 in group 1, 21.1 +/- 3.8 in group 2, and 33.8 +/- 9.2 ml/cmH2O (mean +/- SD) in group 3 (P less than 0.05). Cst was 14.0 +/- 3.5, 10.8 +/- 1.5, and 6.2 +/- 1.2 ml/cmH2O, respectively (P less than 0.01). Pulmonary vascular resistance was 125 +/- 16, 120 +/- 42, and 410 +/- 108 mmHg/L/min (P less than 0.05). We conclude that UW solution is useful for hypothermic canine lung preservation.     

氯胺酮对兔肺缺血/再灌注损伤后细胞凋亡和Caspase-3mRNA表达的影响

目的 观察氯胺酮对兔肺缺血/再灌注损伤后细胞凋亡和Caspase-3 mRNA表达的影响.方法 90只兔建立单肺缺血再灌注模型后,被随机分成3组（每组30只）：对照组（C组）、缺血/再灌注组（I/R组）和氯胺酮组（KET组）.每组30只兔子又平均分成再灌注后1小时、3小时、5小时组.检测各组超氧物歧化物（SOD）活性、丙二醛（MDA）浓度、肿瘤坏死因子α（TNF-α）含量和凋亡指数（AI）变化.图像分析TUNEL染色和原位杂交对肺细胞凋亡及Caspase-3mRNA表达.结果各相同时间点I/R组比C组SOD活性显著降低（P〈0.01）,而MDA、TNF-α含量和AI明显升高（P〈0.01）;与I/R组比较,相同时间点KET组SOD活性升高,而MDA、TNF-α含量和AI则有不同程度降低（P〈0.01或P〈0.05）.肺再灌注后TUNEL法检测阳性细胞主要分布在肺泡上皮细胞和血管内皮细胞,Caspase-3 mRNA表达主要分布在血管内皮细胞;每个时间点I/R组Caspase-3 mRNA表达相比C组显著增加,同时肺细胞凋亡也显著增加.然而,使用氯胺酮后,两者都有明显减少.结论氯胺酮可通过减少缺血/再灌注后MDA、TNF-α含量,提高SOD活性,降低caspase-3 mRNA表达而抑制肺细胞凋亡,减轻再灌注后兔肺损伤.     

缺血预处理对肺缺血再灌注损伤的影响

目的观察缺血预处理（ＩＰＣ）对肺缺血再灌注（Ｉ／Ｒ）损伤的影响。方法建立兔单肺原位热缺血再灌注损伤模型。３０只兔分Ｉ／Ｒ组、ＩＰＣ组和对照组。对比观察各组平均动脉压、动脉血氧分压、肺组织１２５Ｉ标记牛血清白蛋白漏出量、肺湿干重比、髓过氧化物酶活性。结果经９０分钟缺血１８０分钟再灌注后,ＩＰＣ组肺组织１２５Ｉ标记牛血清白蛋白漏出量、肺湿干重比、髓过氧化物酶活性低于Ｉ／Ｒ组（Ｐ＜０．０５）,平均动脉压、动脉血氧分压高于Ｉ／Ｒ组（Ｐ＜０．０５）。结论ＩＰＣ能减轻肺Ｉ／Ｒ导致的肺毛细血管通透性增高、中性粒细胞浸润,减轻肺Ｉ／Ｒ引起的平均动脉压和动脉血氧分压的下降程度,表明ＩＰＣ能减轻肺Ｉ／Ｒ损伤。     

Inhaled NO and prostacyclin during porcine single lung transplantation

Background. Increased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI₂) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft.

Methods. Eighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI₂ (25 μg/mL/30 minutes, 50 μg/mL/30 minutes), or no drugs (control).

Results. In the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI₂ groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI₂. Neither drug improved oxygenation in the graft.

Conclusions. Nitric oxide and PGI₂ decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.     

The effect of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on pulmonary ischemia-reperfusion injury in a canine model

This study evaluates the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on warm ischemia-reperfusion injury of the lung using a canine mode. MATERIALS AND METHODS: Ten adult mongrel dogs weighing 13-16 kg were used. After a left thoracotomy, the left pulmonary artery and vein were clamped. The left main bronchus was also clamped and then divided, and complete ischemia of the left lung was maintained for 3 h. The left main bronchus was re-anastomosed before reperfusion of the left lung. The right pulmonary artery was ligated immediately after reperfusion of the left lung. The dogs were divided into two groups: the DHP-PMX group (n = 5, DHP-PMX was performed for 120 min, from 30 min before reperfusion to 90 min after reperfusion) and the control group (n = 5). The body temperature of the animals was maintained at 36 degrees C-37 degrees C during the experiment. The PaO2/FiO2 (P/F ratio), AaDO2, and lt-pulmonary vascular resistance (PVR) were measured at 30, 60, 120, 180, and 240 min after reperfusion in both groups, and the two groups were compared. The water content of the lung tissues and histopathology was also analyzed. RESULTS: The P/F ratio decreased remarkably after reperfusion in the control group, and was significantly (p < .05) lower than that in the PMX-DHF group until 240 min after reperfusion. The AaDO2 was significantly (p < .05) lower in the DHP-PMX group than in the control group at 30, 60, and 120 min after reperfusion. The lt-PVR level differed significantly (p < .05) between the two groups until 240 min after reperfusion. The water content in the control group was significantly (p < .05) higher than that in the DHP-PMX group at 240 min after reperfusion. Lung tissues at 120 and 240 min after reperfusion were better preserved pathologically in the DHP-PMX group. CONCLUSION: DHP-PMX therapy reduced warm ischemia-reperfusion injury in the lung using a canine model.     

Amelioration of lung reperfusion injury by L- and E- selectin blockade.

OBJECTIVE: Reperfusion injury is the main reason for early graft failure after lung transplantation. Inhibition of the adherence of polymorphonuclear leukocytes to activated endothelium by blocking L- and E-selectins (antibody EL-246) could potentially inhibit reperfusion injury. METHODS: Reperfusion injury was induced in a left lung autotransplant model in sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 h in situ at 15 degrees C. After reperfusion right main bronchus and pulmonary artery were occluded leaving the animal dependent on the reperfused lung (control, n = 6). Pulmonary function was assessed by alveolo-arterial oxygen difference (AaDO2) and pulmonary vascular resistance (PVR), the chemiluminescence of isolated neutrophils, as well as the release of beta-N-acetyl-glucosaminidase (beta-NAG) served as indicator of neutrophilic activation. Extravascular lung water was an indicator for pulmonary edema formation. EL-246 group animals (n = 6) were treated additionally with 1 mg/kg BW of EL-246 given prior and during reperfusion. RESULTS: After 3 h of reperfusion five control animals developed alveolar edema compared to one animal in the EL-246 group (P = 0.08). AaDO2 (mm Hg) was significantly higher in the control compared to the EL-246 group (510 +/- 148 vs. 214 +/- 86). PVR (dyn x s x cm(-5)) was significantly increased in the control compared to the EL-246 group (656 +/- 240 vs. 317 +/- 87). Neutrophilic activation was significantly lower in the EL-246 group. Extravascular lung water was significantly lower compared to control (6.88 +/- 1.0 vs. 13.4 +/- 2.8 g/g blood-free lung weight). CONCLUSIONS: Treatment with EL-246 results in improved pulmonary function and less in vivo PMN activation in this experimental model. Further studies are necessary to evaluate the possible role of selectin blockade in amelioration of reperfusion injury in human lung transplantation.     

PDE-5 inhibitor donor intravenous preconditioning is superior to supplementation in standard preservation solution in experimental lung transplantation.

OBJECTIVE: Improvement of preservation is still a major research objective in lung transplantation. The effects of phosphodiesterase-5 (PDE-5) inhibitors during procurement are still not clear. It was the aim of this study to investigate the effect of sildenafil on post-transplanted lung function in a porcine model using different application procedures. METHODS: In control group lungs were flushed with buffered low-potassium dextran (LPD) solution (I) and compared to LPD solution with supplementation of 0.15 mg/kg body weight (BW) sildenafil (II), whereas in a third group 0.15 mg/kg BW sildenafil was administered intravenously 20 min prior to LPD flushing (III). All grafts were stored for 24 h at 4-6 degrees C. Hemodynamics and blood gases were monitored until 6 h after reperfusion. Lung tissue was taken for wet/dry ratio assessment. RESULTS: All animals of groups I and III survived the entire observation period in contrast to four animals of group II which died within 4 h after reperfusion due to severe reperfusion injury. Group II showed a lower mean PAP and a reduced pulmonary vascular resistance (PVR) throughout the observation period, but did not reach significance due to low number of surviving animals. Group III achieved significantly improved PO2/FiO2 fraction at all timepoints and a significant reduced PVR [434+/-98 vs 594+/-184 dyn s cm(-5), II vs I; mean+/-SD, p<0.01] at 6 h. Wet/dry ratio was significantly higher in group II throughout the experiment. CONCLUSIONS: Sildenafil allows for a better graft function after 24 h ischemia when given prior to standard flushing and preservation. This effect can be explained by a complete/homogenous preservation achieved by selective pulmonal vasodilatation. However, this effect seems to persist when sildenafil remains in the storage solution, leading to severe pulmonary edema.     

Pulmonary preservation with LPD and celsior solution in porcine lung transplantation after 24 h of cold ischemia.

OBJECTIVE: Pulmonary preservation for transplantation is associated with ischemia reperfusion injury resulting in endothelial cell and surfactant dysfunction. The purpose of the study was to compare two extracellular type solutions, low potassium dextrane (LPD) and Celsior in their ability of ameliorating lung ischemia reperfusion injury. METHODS: In 12 donor pigs, the left lung was perfused with either LPD (n = 6) or Celsior (n = 6) solution. After 24 h cold storage, the lungs were transplanted into 12 recipient animals. After reperfusion of the left lung, the right pulmonary artery and bronchus were clamped. Bronchoalveolar lavage fluid (BALF) was obtained before the surgical procedure and 2 h after reperfusion. Surfactant activity was measured from BALF using a pulsating bubble surfactometer. Hemodynamic and respiratory parameters were assessed in 30-min intervals for 7 post-operative hours. RESULTS: In both study groups two of six animals died from severe ischemia reperfusion injury, thus survival did not differ between groups. Rise of pulmonary vascular resistance index (P = 0.01) and sequestration of neutrophiles (P = 0.08) was less pronounced in Celsior group when compared to LPD animals. A difference in surfactant activity between both groups was not evident after 2 h of reperfusion. CONCLUSIONS: Both solutions might provide safe pulmonary preservation for 24 h of cold ischemia. While surfactant activity was affected to the same extent in both groups, Celsior solution provided slightly superior endothelial preservation.     

Role of inhaled nitric oxide in ischaemia-reperfusion injury in the perfused rabbit lung

We have tested if inhaled nitric oxide (NO) is beneficial in ischaemia- reperfusion (IR) lung injury using an isolated perfused rabbit lung model. Ischaemia for 60 min was followed by reperfusion and ventilation with nitric oxide 40 ppm (n = 6) or without nitric oxide ventilation (n = 6) for 60 min. In the control group (n = 6), the lungs were perfused continuously for 120 min. Permeability coefficient (Kfc) and vascular resistance (PVR) were measured serially for 60 min after reperfusion. We also determined the left lung W/D ratio and measured nitric oxide metabolites (NOx) and cGMP concentrations in bronchoalveolar lavage (BAL) fluid from the right lung. IR increased Kfc, PVR and W/D followed by decreased cGMP. Ventilation with nitric oxide restored these changes by preventing the decrease in cGMP. Differences in NOx concentrations in BAL fluid between the control and IR groups were not statistically significant. Our results indicate that IR impaired pulmonary vascular function and resulted in microvascular constriction and leakage. Ventilation with nitric oxide from the beginning of the reperfusion period improved pulmonary dysfunction such as vasoconstriction and capillary leak by restoring cGMP concentrations.