无心跳供体肺的研究现状

肺移植作为晚期肺部疾病的一种有效治疗方法 ,在世界范围内得到广泛的开展 ,但病例数却一直得不到显著的提高 ,其中一个重要原因就是满意的供体肺的严重短缺。在传统的肺移植中 ,人们使用的移植肺都来自循环完整的脑死亡患者。 1986年 ,Ｌｅｃｈｎｅｒ等用从尸体中获得的肺上皮细胞进行培养 ,获得了成功[1] 。这一结果提示 :血液循环停止后 ,完整肺功能具有可恢复性。于是 ,“无心跳供体” (ｎｏｎ ｈｅａｒｔ ｂｅａｔｉｎｇｄｏｎｏｒ,ＮＨＢＤ)的提出成为了必然。目前 ,无心跳供体器官移植的经验还大多集中在肾移植、肝移植 ,其应用于肺…     

无心跳供体肺移植

本文综述了无心跳供体肺的热缺血时限、保护措施、无心跳供体的死亡原因对供肺功能的影响、供体心跳停止前预处理及移植厚损害修复等方面的研究进展。     

依布西林对大鼠无心跳供体肺的保护作用

目的 观察依布西林在大鼠无心跳供体(NHBD)肺保护中的作用.方法 将60只SD大白鼠随机分为A组:有心跳供体(HBD)组;B组:NHBD组;C组:NHBD+依布硒林(Ebselen)组.B组、C组供体处死后维持辅助呼吸,放置室温中30 min,再灌注低钾右旋糖苷(LPD)液.受体鼠行"原位左肺移植术".C组受体在肺移植前1 h给予Ebselen.结果 C组移植后肺顺应性为0.1740±0.0100,结扎右肺门后15、30 min动脉血氧分压分别为(93.97±5.94)、(92.30±6.57)mm-Hg,肺组织丙二醛(MDA)含量为(0.63±0.23)nmol/mg蛋白,肺组织能量代谢物总量为(821.51±29.70)mol/g,与B组比较差异均有统计学意义(P＜0.05).结论 给予受体一定浓度的Ebselen可改善NHBD肺保护作用.

Abstract：

Objective To evaluate the protective effect of ebselen on the rat lungs from non-heartbeating donors (NHBD). Methods Sixty Sprague-Dawley rats were randomly divided into 3 groups:group A, heart-beating donor; group B, NHBD with 30 min of warm ischemia time (WIT); group C, NHBD with 30 min of WIT and administration of ebselen. The donor lungs in groups B and C maintained ventilation at room temperature for 30 min after asystolia and then were flushed with LPD solution. The recipient rats underwent left lung transplantation. The recipients in group C were administered with ebselen 1 h before transplantation. Results All the recipients survived during the observation period. The pulmonary compliance of group C was 0. 1740 ±0. 0100. The PaO2 at 15 min and 30 min after the ligation of the right pulmonary hila was (93.97 ±5.94), (92. 30 ±6. 57) mmHg, respectively. Malondialdehyde (MDA) of the pulmonary tissue was (0. 63 ±0. 23) nmol/mg pro and the energy metabolism was (821.51 ±29.70)mol/g. The difference between group B and group C was significant (P ＜ 0. 05 ). Conclusion The administration of ebselen is a safe and effective treatment in the preservation of the rat lungs from NHBD.     

无心跳供体的研究进展及在肺移植中的应用

无心跳供体作为肺移植供体的一个重要来源,已成功应用于临床多年,且预后良好。而供体的短缺、肺保护的不完善和伦理学上的争议仍制约着无心跳供体的发展。近年来随着科学的不断进步,无心跳供体各方面研究已取得很大进展,本文就无心跳供体的分类、缺血时间、死亡的判定、伦理学上的进展、供肺保护等方面进行综述。     

低浓度一氧化碳通气减轻无心跳供体肺的热缺血损伤

目的 探讨低浓度一氧化碳通气对无心跳供体(NHBD)移植肺组织的热缺血损伤保护机制.方法 对供体大鼠NHBD给予低浓度CO机械通气,利用大鼠左肺移植动物模型进行研究;再灌注后测定动脉血气分析、移植肺组织湿/干(W/D)重量比、髓过氧化物酶(MPO)活性和支气管肺泡灌洗液(BAL)中中性粒细胞计数等参数,同时检测移植肺组织中前炎症因子IL-1β和凋亡相关基因caspase 3的表达量.结果 移植肺再灌注后1、2和4 h CO组的动脉血氧分压均显著大于对照组.再灌注4 h后,对照组的W/D重量比值、MPO活性值以及BAL中性粒细胞计数均明显大于CO组.CO组移植左肺组织的IL-1β和caspase 3基因的mRNA相对表达量均显著低于对照组IL-1β和caspase 3基因的mRNA相对表达量.结论 低浓度CO机械通气可以通过抑制前炎症因子IL-1β和凋亡相关基因caspase 3表达的机制减轻NHBD供肺的热缺血损伤.     

热缺血期间持续通气对无心跳兔肺的保护作用

目的:研究热缺血期间持续通气对无心跳供者(NHBD)的肺的保护作用。方法:将12只日本大耳白兔作为供者，随机分为两组，在无肝素抗凝处理条件下处死动物，经历热缺血1h。对照组热缺血期间不给予通气，实验组热缺血期间给予持续通气，然后均以4℃ Euro-Collins液灌洗，冷保存2h。另取同种兔12只，建立离体兔肺灌注模型，对保存的兔肺进行再灌注。分别评价血流动力学、肺泡细胞生存能力、组织学改变、血液气体分析及湿干比。结果:实验组与对照组相比，肺血管阻力较低，肺泡细胞生存能力较高，肺血管内血栓数较少，动脉血氧分压较高，湿干比较低。病理学检查，实验组肺损伤程度较对照组轻。结论:热缺血期间的持续通气对无肝素抗凝处理的无心跳供者的肺具有明显的保护作用。     

大白鼠无心跳供体肺移植的实验研究

目的　探讨不同热缺血时间对无心跳供体肺的组织结构和功能的影响及无心跳供体肺应用于肺移植的可能性。　方法　取 6 0只健康大白鼠 ,随机分成有心跳组、无心跳 缺血 30min组、无心跳 缺血 6 0min组 ,每组 10对 ,分别为供体和受体。有心跳组供体在处死的同时灌注 4℃低钾右旋糖苷液 ,无心跳 缺血 30min组、无心跳 缺血 6 0min组供体处死后维持辅助呼吸 ,分别放置室温中30和 6 0min ,再灌注低钾右旋糖苷液 ,供肺置于 4℃低钾右旋糖苷液中 4h。受体鼠行左侧开胸术和原位左肺移植术。术后维持辅助呼吸 1h ,经右侧进胸 ,阻断右肺门。　结果　无心跳 缺血 30min组存活时间均超过 30min ,肺顺应性为 0 .16 4 0± 0 0 0 4 9,动脉血氧分压 (85± 4 )mmHg ,动脉血二氧化碳分压 (41 9± 1 9)mmHg ,腺苷核苷酸总量 (75 8± 30 )mol/ g蛋白 ,超微结构改变为轻度的淤血和肺实质水肿 ,与有心跳组相比 ,差异均无显著意义 (P >0 0 5 )。无心跳 缺血 6 0min组有 4只 10min后心跳停止 ,3只 2 0min后心跳停止 ,与另两组相比 ,所测各项指标的差异有显著意义 (P <0 0 5 )。　结论　采用无心跳供体是增加供肺来源的一种安全而有效的方法 ,热缺血 30min大白鼠无心跳供体肺适于肺移植。     

LPD液对无心跳供体肺的保护作用

目的 从肺组织病理学角度，评价低钾右旋糖酐（LPD）液对无心跳供体（NHBD）肺的保护作用。方法 左侧供体肺使用LDP液采用顺行和逆行灌注技术。对在4℃灌注液中保存6、12、18、24h和缺血-灌注1h的标本行组织病理学检查。结果 随着冷保存时间的延长，供体肺组织病理变化并不明显。仅12、18和24h组可见灶状肺泡萎陷；缺血-再灌注组的肺小动脉及血管内充血，部分肺泡壁血管充血伴周围炎性细胞渗出。结论 LPD液可以安全的应用于临床尸体肺移植术。LPD液优良的保存效果使其可以扩大供体肺的数量和延长供体肺的安全缺血时限。     

缺血预处理对犬肺移植供肺的保护作用

采用犬异体肺移植模型，评价缺血预处理对肺缺血再灌注损伤的保护作用。结果预处理组在移植徨肺静脉血和肺组织中的超氧化物歧化酶，氧自由基最终产物丙二醛的含量发迹与对照组比较，差异有显著性。     

部分液体通气对急性肺损伤兔肺表面活性物质的影响

目的 研究部分液体通气(PLV)对油酸诱导的急性肺损伤肺表面活性物质的影响。方法 24只健康成年日本大白兔随机分成三组,每组8只:正常对照单纯机械通气组(C组);油酸肺损伤机械通气组(MV组)和油酸肺损伤部分液体通气组(PLV组)。中心静脉滴注油酸150μg/kg诱导急性肺损伤(ALI)模型,1h后当PaO_2/FiO_2<300时,认为造模成功,再连续通气4h,用多导生理监测仪连续记录血压和心率的变化,并测定基础、肺损伤及治疗后1、2、4h动脉血气。治疗4h立即处死动物,描记肺的压力-容积曲线,行右肺支气管灌洗,测量灌洗液中双饱和磷脂酰胆碱(DPPC)、肺表面活性物质相关蛋白A(SP-A)、总蛋白(TP)的浓度。结果 PLC组经PLV治疗后,PaO_2提高(P<0.01),各时段PaO_2高于MV组(P<0.01);PLV组PaCO_2逐渐降低,治疗后4h,PaCO_2与MV组差异有显著性(P<0.05)。PLV组灌洗液中DPPC、SP-A的含量高于MV组(P<0.01),而TP的含量低于MV组(P<0.01)。PLV组肺的顺应性较MV组提高。结论 PLV可增加油酸性急性肺损伤肺泡Ⅱ型上皮细胞分泌肺泡表面活性物质,改善肺功能。     

完全液体通气减轻乳猪体外循环术后肺炎症反应的实验研究

目的探讨以全氟化碳为载体的完全液体通气对乳猪体外循环(CPB)术后肺气体交换及炎症反应的影响。方法CPB术后肺损伤的乳猪分为完全液体通气组和传统机械通气组,每组6只。分别在CPB前、CPB后每30min行动脉血气分析。通气4h后取右下肺行支气管肺泡灌洗,检测灌洗液白细胞介素6、8和髓过氧化物酶水平并行细胞计数;取左下肺行病理分析。结果两组动脉血氧分压和二氧化碳分压比较差异无统计学意义。实验组肺泡灌洗液白细胞介素6(53.55±15.48)pg/ml对(81.32±15.23)pg/ml(P<0.05),髓过氧化物酶浓度(50.00±7.37)U/L对(75.00±9.19)U/L(P<0.05),均显著低于机械通气组;而白细胞介素8水平两组比较差异无统计学意义。光镜检查显示完全液体通气组肺组织损伤明显减轻。结论完全液体通气能维持乳猪CPB术后正常的气体交换功能;可明显减轻乳猪CPB术后肺部炎症反应和组织学损伤。     

术侧肺部分通气法与单肺通气的比较研究

目的 与单肺通气(one-lung ventilation,OLV)比较术侧肺部分通气(partial ventilation of independent lung,PLV)情况下的氧合与气道压力.方法 16例接受食道手术的患者随机分为两组,进行自身对照交叉研究.在双肺通气后按不同顺序接受OLV和术侧肺PLV,比较3种通气时氧合指数(oxygen index,OI)及气道压力的变化.结果 两种通气方式下OI均显著低于双肺通气(two-lung ventilation,TLV),但PLV时显著高于OLV(PLV391±112,OLV134±53,TLV530±92,P<0.05);气道压力值在PLV时也显著低于OLV[Ppeak:(19±3)cm H2O vs(27±5)cm H2O,Pplat:(17±2)cm H2O vs(23±3)cm H2O,P<0.05](1 cm H2O=0.098 kPa). 结论PLV显著改善了氧合和呼吸力学指标.     

术侧肺部分通气法与单肺通气的比较研究

Objective The purpose of this study was to compare oxygenation and airway pressure during partial ventilation of the independent lung( PLV) with one-lung ventilation(OLV). Methods 16 patients undergoing thoracotomy for esophageal carcinoma were randomized divided into two groups and a self -controlled cross -over study was used. Two types of ventilation was used in different sequence after two-lung ventilation(TLV), oxygenation index( OI) and airway pressure was compared between groups. Results OI was significantly lower during OLV and PLV than TLV, while it was significantly higher during PLV than OLV (PLV391±112, OLV134±53, TLV530±92,P<0.05). Airway pressure was also significantly lower during PLV than OLV[Ppeak: (19±3) cm H20 vs(27±5) cm H2O,Pplat: (17±2) cm H2O vs (23±3) cm H20, P<0.05 ]. Conclusion PLV significantly improve oxygenation and respiratory mechanics.     

术侧肺部分通气法与单肺通气的比较研究

Objective The purpose of this study was to compare oxygenation and airway pressure during partial ventilation of the independent lung( PLV) with one-lung ventilation(OLV). Methods 16 patients undergoing thoracotomy for esophageal carcinoma were randomized divided into two groups and a self -controlled cross -over study was used. Two types of ventilation was used in different sequence after two-lung ventilation(TLV), oxygenation index( OI) and airway pressure was compared between groups. Results OI was significantly lower during OLV and PLV than TLV, while it was significantly higher during PLV than OLV (PLV391±112, OLV134±53, TLV530±92,P<0.05). Airway pressure was also significantly lower during PLV than OLV[Ppeak: (19±3) cm H20 vs(27±5) cm H2O,Pplat: (17±2) cm H2O vs (23±3) cm H20, P<0.05 ]. Conclusion PLV significantly improve oxygenation and respiratory mechanics.     

乌司他丁对单肺通气麻醉患者肺缺血-再灌注损伤的保护作用

目的 观察乌司他丁对全麻单肺通气(OLV)肺叶切除术患者肺缺血-再灌注损伤的保护作用.方法 全麻下OLV肺叶切除术患者20例,随机均分为观察组(A组)和对照组(B组).A组OLV开始后,静脉泵注乌司他丁10 000 U/kg,1 h内注完;B组给予同量生理盐水.胸内手术操作结束恢复双肺通气(TLV).两组分别在麻醉前(T0)、手术开始0.5 h(T1)、1 h(T2),2 h(T3)、术后1 h (T4)、2 h(T5)、24 h(T6)、48 h(T7)8个时点采血行多形核白细胞(PMN)计数,测黄嘌呤氧化酶(XOD)和髓过氧化物酶(MPO)活性.结果 两组PMN计数差异无统计学意义.与T0比较,两组PMN计数在T4～T7时明显升高(P＜0.05).A组XOD和MPO活性均明显小于B组(P＜0.05或P相似文献   

The mode of death in the non-heart-beating donor has an impact on lung graft quality

Objective: We hypothesised that the agonal phase prior to cardiac death may negatively influence the quality of the pulmonary graft recovered from non-heart-beating donors (NHBDs). Different modes of death were compared in an experimental model. Methods: Non-heparinised pigs were divided into three groups (n = 6 per group). Animals in group I [FIB] were sacrificed by ventricular fibrillation resulting in immediate circulatory arrest. In group II [EXS], animals were exsanguinated (45 ± 11 min). In group III [HYP], hypoxic cardiac arrest (13 ± 3 min) was induced by disconnecting the animal from the ventilator. Blood samples were taken pre-mortem in HYP and EXS for measurement of catecholamine levels. After 1 h of in situ warm ischaemia, unflushed lungs were explanted and stored for 3 h (4 °C). Left lung performance was then tested during 60 min in our ex vivo reperfusion model. Total protein concentration in bronchial lavage fluid was measured at the end of reperfusion. Results: Pre-mortem noradrenalin (mcg l⁻¹) concentration (baseline: 0.03 ± 0) increased to a higher level in HYP (50 ± 8) vs EXS (15 ± 3); p = 0.0074. PO₂ (mmHg) at 60 min of reperfusion was significantly worse in HYP compared to FIB (445 ± 64 vs 621 ± 25; p < 0.05), but not to EXS (563 ± 51). Pulmonary vascular resistance (dynes s cm⁻⁵) was initially higher in EXS (p < 0.001) and HYP (NS) vs FIB (15824 ± 5052 and 8557 ± 4933 vs 1482 ± 61, respectively) but normalised thereafter. Wet-to-dry weight ratio was higher in HYP compared to FIB (5.2 ± 0.3 vs 4.7 ± 0.2, p = 0.041), but not to EXS (4.9 ± 0.2). Total protein (g l⁻¹) concentration was higher, although not significant in HYP and EXS vs FIB (18 ± 6 and 13 ± 4 vs 4.5 ± 1.3, respectively). Conclusion: Pre-mortem agonal phase in the NHBD induces a sympathetic storm leading to capillary leak with pulmonary oedema and reduced oxygenation upon reperfusion. Graft quality appears inferior in NHBD lungs when recovered in controlled (HYP) vs uncontrolled (EXS and FIB) setting.     

Protective ventilation to reduce inflammatory injury from one lung ventilation in a piglet model

Objectives: To test the hypothesis that protective ventilation strategy (PVS) as defined by the use of low stretch ventilation (tidal volume of 5 ml·kg^?1 and employing 5 cm of positive end expiratory pressure (PEEP) during one lung ventilation (OLV) in piglets would result in reduced injury compared to a control group of piglets who received the conventional ventilation (tidal volume of 10 ml·kg^?1 and no PEEP). Background: PVS has been found to be beneficial in adults to minimize injury from OLV. We designed the current study to test the beneficial effects of PVS in a piglet model of OLV. Methods: Ten piglets each were assigned to either ‘Control’ group (tidal volume of 10 ml·kg^?1 and no PEEP) or ‘PVS’ group (tidal volume of 5 ml·kg^?1 during the OLV phase and PEEP of 5 cm of H₂O throughout the study). Experiment consisted of 30 min of baseline ventilation, 3 h of OLV, and again 30 min of bilateral ventilation. Respiratory parameters and proinflammatory markers were measured as outcome. Results: There was no difference in PaO₂ between groups. PaCO₂ (P < 0.01) and ventilatory rate (P < 0.01) were higher at 1.5 h OLV and at the end point in the PVS group. Peak inflating pressure (PIP) and pulmonary resistance were higher (P < 0.05) in the control group at 1.5 h OLV. tumor necrosis factor‐alpha (P < 0.04) and IL‐8 were less (P < 0.001) in the plasma from the PVS group, while IL‐6 and IL‐8 were less (P < 0.04) in the lung tissue from ventilated lungs in the PVS group. Conclusions: Based on this model, PVS decreases inflammatory injury both systemically and in the lung tissue with no adverse effect on oxygenation, ventilation, or lung function.     

部分液体通气与吸入NO对急性肺损伤动物疗效的对比研究

目的对肺灌洗(Lavage)诱导的急性肺损伤(ALI)家猪实施以氟碳(PFC)为媒介的部分液体通气(PLV)及吸入20ppm的一氧化氮(NO),比较二者对肺气体交换及血液动力学的影响.方法24头健康家猪,麻醉后经气管导管肺内以生理盐水反复灌洗,直至动脉氧分压(PaO2)<100mmHg达1h,记录气体交换及血液动力学各参数作为急性肺损伤的基础值.随机分为PLV组、NO组及对照组,PLV组肺内灌以相当于肺功能余气量(30ml/kg)的PFC,然后以普通呼吸机行常规气体通气,补充PFC4ml·kg-1·h-1以弥补蒸发损失;NO组吸入20ppmNO,对照组不给予其它治疗,各组每小时记录气体交换及血液动力学各参数的变化.结果PLV组实施PLV1h后,PaO2即从ALI时的(53±11)mmHg升高至(142±133)mmHg,4h后达(318±109)mmHg,与ALI时比较差异有显著性(P＜0.01),亦显著高于对照组(P＜0.05).实施PLV1h后Qs/Qt从ALI时的(57±9)%降至(42±13)%,4h后降至(26±10)%,较ALI时差异有显著性(P＜0.01),并于2h后显著低于对照组(P＜0.05).NO组的MPAP在整个实验过程中显著低于对照组(P＜0.01).NO组吸入NO1h后,PaO2即呈上升趋势,4h后从ALI时的65±14升至(114±36)mmHg,与对照组比较差异有显著性(P＜0.05).同时肺内分流(Qs/Qt)及肺泡-动脉氧压差(AaDO2)降低.MAP及体循环血管阻力(SVR)与对照组比较无显著性改变.结论以氟碳为媒介的部分液体通气及吸入20ppm的NO均能有效的改善ALI动物肺气体交换.吸入NO能显著降低MPAP,而PLV更能显著的升高PaO2.