HOE-642联合尼可地尔对无心跳猪供心的保护作用

目的 探讨无心跳供者(NHBD)的心脏进行移植的可行性,以及HOE-642联合尼可地尔对这种供心的保护效果.方法 将健康雄性家猪随机分为实验组和对照组,实验组供者采取主动脉快速完全放血法制成NHBD模型,取其心脏,冷保存4 h后进行移植;对照组供者经主动脉适量放血(仍有心跳),造成热缺血,然后取其心脏,冷保存4 h后进行移植.实验组于供心热缺血前5 min静脉给予HOE-642(2 mg/kg);以含HOE-642和尼可地尔的4 ℃ Stanford液灌洗和保存供心;供心吻合前经主动脉根部以含HOE-642和尼可地尔的4 ℃ 4:1血心停搏液(高钾)灌注1次;供心吻合期间以含HOE-642和尼可地尔的4 ℃ 4:1血心停搏液(低钾)间断灌注;心脏吻合完毕主动脉开放后初始5 min时段内,静脉给予HOE-642(2 mg/kg).对照组的供心处理除不用HOE-642和尼可地尔外,其余同实验组.采集供心主动脉根部放血前、移植心脏吻合完毕主动脉开放后1 h(停机)以及主动脉开放后2 h(实验结束)3个时点的心脏血流动力学指标,测定移植心脏的心肌含水量,观察心肌的组织学变化.结果 两组在主动脉开放后心肌红润,心脏搏动有力,均成功脱机.两组各检测时点的左心室舒张末压、左心室峰发展压及左心室压力变化速率的差异均无统计学意义(P＞0.05);实验组和对照组心肌组织含水量分别为(78.6±5.7)%和(76.4±4.2)%,其差异无统计学意义(P＞0.05);光镜下见两组的心肌纤维结构清楚,排列紧密,间质未见炎症细胞浸润,也未见变性、坏死,无排斥反应征象,电镜下见心肌细胞超微结构完整.结论 NHBD的供心可用于移植,其效果与有心跳者相近;HOE-642和尼可地尔联用可能对该类供心具有一定的保护作用.     

缺血预处理对犬心移植供心的保护作用

12只供心犬均分为两组。实验组在心脏摘下前施行缺血预处理(3分钟主动脉钳闭,2分钟低流量灌注,10分钟再灌注),对照组则直接摘下心脏。两组心脏均经4℃Euro-Collins液保存后原位植入受心犬胸内。进行术中、术后心肌观察及心肌酶学、血流动力学、心电改变等项研究。结果提示:缺血预处理对犬心移植中供心具有良好的心肌保护作用,能减轻心肌组织损伤程度,降低心肌收缩力下降幅度,减少室性心律失常的发生率。     

心脏移植术中供心的保护

目的 为了提高心脏移植的效果,改进心脏移植中供心的保护方法。方法 ３例原位心脏移植手术中采用４℃改良Ｓｔ,Ｔｈｏｍａｓ液经主动脉根部灌注和温血２６￣３４℃逆行状静脉窦灌注方法保护供心。结果 主动脉开放后,各项血液动力学指标在正常范围、心肌超微结构保持完整,未见缺血损害,长期随访心功能Ⅰ级,恢复正常生活和工作。结论 温血逆行冠状静脉窦灌注适合心脏移植中供心的保护。     

温血心停跳液持续灌注对心内直视术中犬心肌细胞质膜的保 …

目的 观察温血心停跳液持续灌注对心内直视术中犬心肌细胞质膜的保护作用。方法 采用温血心停跳液持续灌注或冷晶体改停跳液间断灌注（ＩＣＣＣ）作心肌保护。以镧（Ｌａ＾３＋）标记电镜技术观察心肌细胞质膜通透性的改变。结果 主动脉阻断关,两组心肌组织中Ｌａ＾３＋局限在心肌细胞外间隙沉积;再灌注后６０分钟对照组心肌细胞线粒体内,周边及肌原纤维上有Ｌａ＾３＋沉积,实验组心肌细胞内无Ｌａ＾３＋沉积。     

大鼠供心转染CTLA4-Ig基因抑制心脏移植后排斥反应

目的研究大鼠供心转染CTLA4-Ig基因抑制心脏移植术后排斥反应的可行性。方法以BN大鼠为供者,Lewis大鼠为受者,建立心脏移植模型。将实验分为2组。对照组:供心获取过程中不给予任何干预处理;实验组:在供心获取的过程中,以质粒载体携带CTLA4-Ig(pUF1-CTLA4-Ig)经过冠状动脉灌注供心。采用逆转录聚合酶链反应(RT-PCR)检测供心组织中CTLA4-IgmRNA的表达,观察移植心存活时间;酶联免疫法(ELISA)检测血清γ-干扰素(IFN-γ)和白细胞介素-4(IL-4)水平;观察移植心的组织学改变;用免疫组织化学SABC法检测移植心组织中CD4 和CD8 T细胞的浸润。结果实验组移植心存活时间较对照组明显延长[(11.70±1.24)dvs(5.62±0.74)d,P<0.05]。移植后5d,实验组移植心组织中可见CTLA4-IgmRNA的表达;对照组病理学检查可见心肌间质出现弥漫性的炎性细胞浸润,伴有局部的心肌坏死,组织间质水肿,实验组仅有局灶性血管外周及心肌间质内炎性细胞浸润,未见坏死;对照组移植心组织中浸润的CD4 和CD8 T细胞数量明显高于实验组(P<0.01);实验组血清IFN-γ水平明显低于对照组(P<0.01),但血清IL-4水平差异无统计学意义(P>0.05)。结论经冠状动脉灌注转染CTLA4-Ig基因,可以抑制心脏移植后排斥反应。     

温血心停跳液持续灌注对心内直视术中犬心肌细胞质膜的保护作用

目的观察温血心停跳液持续灌注对心内直视术中犬心肌细胞质膜的保护作用。方法采用温血心停跳液持续灌注（ＣＷＢＣ）或冷晶体心停跳液间断灌注（ＩＣＣＣ）作心肌保护。以镧（Ｌａ３＋）标记电镜技术观察心肌细胞质膜通透性的改变。结果主动脉阻断前，两组心肌组织中Ｌａ３＋局限在心肌细胞外间隙沉积；再灌注后６０分钟，对照组心肌细胞线粒体内、周边及肌原纤维上有Ｌａ３＋沉积，实验组心肌细胞内无Ｌａ３＋沉积。结论①Ｉ／Ｒ损伤后早期，心肌细胞质膜通透性增高；②ＣＷＢＣ可以减轻心肌损伤，很好地维持心肌细胞质膜的完整性。     

总结69例心脏移植中供心的心肌保护技术

目的总结心脏移植中供心的心肌保护技术，分析供心的灌注、保存以及缺血时间对心脏移植效果的影响。方法回顾性分析2004年6月至2006年9月间的69例晚期心脏病患者行心脏移植术的临床资料。供心的心肌保护采用低温St．Thomas液和HTK液顺序灌注方法，术中供心保持持续低温状态。根据供心缺血时间长短将受者分为两组，A组36例，供心缺血时间小于240min；B组33例，供心缺血时间大于240min。术后对受者进行定期随访。结果在心脏移植术中，B组受者较A组的体外循环时间延长。术后两组受者的死亡率、移植心功能、排斥反应以及并发症等资料的比较，差异无统计学意义（P〈0．05）。所有受者在心脏移植后，无近期死亡，但随访期间死亡6例。结论采用St．Thomas液和HTK液顺序冷灌注的改良方法，能够有效的保护供心心肌组织；供心缺血时间的缩短会使心肌泵血功能恢复较快。这些对移植心功能的恢复和受者的预后具有良好的近期和中期效果。     

改良心肌保护液对不同时间热缺血供心移植效果的影响

目的研究对短暂常温热缺血的猪供心采用改良心肌保护液低温保存后对供心结构和功能的保护作用。方法建立猪原位心脏移植模型,分别采用St.Thomas液灌注和改良心肌保护液保存供心。24只家猪随机分为对照组(C组)、5min热缺血组(W1组)、10min热缺血组(W2组)和改良心肌保护液组(E组)。C组,低温灌注后切取供心,4℃保存4h和心脏移植后测定心肌含水率(MWC)、丙二醛(MDA)、三磷酸腺苷(ATP)含量和心脏超微结构观察;W1组,供心灌注低温保护液前常温缺血5min,余同C组;W2组,供心灌注低温保护液前常温缺血10min,余同C组;E组,供心常温缺血5min后用改良保护液灌注和保存,余同C组。均采用标准法移植心脏。心脏移植后观察移植后供心复跳情况、平均动脉压、心排血量(CO)及早期肌钙蛋白I(cTnI)的漏出水平。结果W1和W2组供心低温保存后MWC、MDA高于C组,而ATP明显降低(P<0.05);E组与C组相比,供心低温保存后MWC、MDA增高,ATP减少(P>0.05);超微结构,W1组损伤较C组和E组明显加重,W2组损伤呈不可逆改变。供心移植后,C组和E组cTnI漏出少,血液动力学指标好于W1、W2组(P<0.05)。结论改良心肌保护液可有效改善供心因短暂常温热缺血而造成的结构和功能损害。供心灌注低温保护液前常温缺血10min可造成供心不可逆改变。     

经二氮嗪强化的Celsior液延长大鼠供心冷保存时间的研究

目的 研究经二氮嗪强化的Celsior液对延长大鼠供心冷保存时间的作用及机制.方法 选取近交系雄性SD大鼠作为心脏移植的供、受者.根据供心保存液的不同分为对照组和实验组,每组24只.再根据供心保存时间的不同,将对照组和实验组各随机平均分为3组:对照5、8和10 h组,分别将供心置于低温单纯Celsior液中保存5、8和10 h;实验5、8和10 h组,分别将供心置于含30/μmol/L二氮嗪的低温Celsior液中保存5、8和10 h.各组供心在保存相应时间后进行大鼠颈部异位心脏移植.术后观察和比较各组供心移植后的复跳率、心肌丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、ATP酶活性、Caspase-3蛋白的表达水平、心肌细胞凋亡以及心肌超微结构的变化.结果 供心血流开放30 s内,实验8和10 h组心脏复跳率较相应对照组显著提高;在相同保存时间下,实验组较对照组心肌MDA含量明显降低、SOD活性和心肌ATP酶活性明显增强以及Caspase-3蛋白表达和心肌细胞凋亡减少;各实验组和对照5 h组心肌超微结构清晰、完整;对照8和10 h组心肌超微结构受到不同程度的损伤.结论 经二氮嗪强化的Celsior液能够有效延长大鼠供心的冷保存时间,其作用机制可能与二氮嗪减轻供心的缺血再灌注损伤有关.     

热缺血后低温保存对供心的影响

目的　观察常温短暂热缺血后低温保存对供心的影响。方法　建立猪原位心脏移植模型 ,随机分为对照组 (C组 )和热缺血组 (H组 )。H组供心切取前常温缺血 5min。供心 4℃保存4h测定含水率、MDA、ATP含量 ,原位末端标记法检测心肌细胞凋亡 ;两组供心行原位心脏移植各8例 ,观察移植后血浆肌钙蛋白I(cTnI)水平、心排量 (CO )和再灌注 2h的心肌超微结构和凋亡。结果　与C组比较 ,H组供心低温保存后含水率、MDA高于C组 ,而ATP明显降低 ,差异均有显著性 (P <0 .0 5 ) ;C组cTnI漏出少 ,CO高于H组 (P <0 .0 5 ) ;H组心肌细胞结构改变明显 ,凋亡水平高于C组 (P <0 .0 1)。结论　热缺血使供心能量消耗 ,诱导再灌注后心肌细胞凋亡 ,一定程度上导致了供心移植后早期功能异常。     

The effect of graft perfusion with warm blood cardioplegia for cadaver heart transplantation

This study was designed to verify the effect of reperfusion of donor hearts in a perfusion apparatus after 60 min of global ischemia prior to heart transplantation. Thirteen dogs were exsanguinated from the femoral artery and cardiac arrest was achieved. The hearts were left in situ at room temperature (25°C)for 60 min. In group A (n=7), the hearts were excised and reperfused 60 min after cardiac arrest in the perfusion apparatus with substrate-enriched warm blood cardioplegia (WBCP) containing a hydroxyl radical scavenger, EPC, followed by 45 min of blood perfusion, Next, the hearts were preserved in cold (4°C) University of Wisconsin (UW) solution. In group B (n=6), the hearts were perfused with cold (4°C) St. Thomas' solution 60 min after cardiac arrest and preserved in cold UW solution. Thereafter, all hearts in both groups were transplanted orthotopically to recipient dogs. In group A, 6 of 7 dogs were weaned from cardiopulmonary bypass (CPB). In group B, only 2 of 6 dogs were weaned from CPB. Moreover, 3 of the 6 hearts in group B did not start beating after transplantation (stone heart). This study suggested reperfusion of the donor heart in the perfusion apparatus with WBCP to be a beneficial preconditioning method when utilizing 60-min arrested hearts for transplantation. This study was supported in part by Senju Pharmaceutical Co. Ltd., Osaka, Japan     

Optimal Conditions for Oxygenated Subnormothermic Machine Perfusion for Liver Grafts Using a Novel Perfusion Device

BackgroundLiver transplantation from donors after cardiac death (DCD) resolves donor shortages.PurposeWe investigated the optimal time for subnormothermic oxygenated perfusion in DCD liver transplantation.MethodsTen F1 pigs (body weight: 27-32 kg) were allocated to 2 groups: the heart beating group (n = 6), from which livers were retrieved while the heart was beating, and the donation after cardiac death (DCD) group (n = 4), in which liver retrieval was performed on pigs under apnea-induced cardiac arrest for 20 minutes. In both groups, the livers were kept in cold storage for 2 hours after retrieval and perfused with a subnormothermic oxygenated Krebs-Henseleit buffer for 120 minutes. We used a novel perfusion device, which can set maximum perfusion pressures of arteries and portal vein, developed by Asahikawa Medical University and Chuo Seiko Co. Bile production, liver enzymes, and inflammatory cytokines were measured and the sinusoidal space, using tissue specimens taken from liver grafts, was measured at 30, 60, 90, and 120 minutes after the start of perfusion.ResultsBile production peaked at 90 minutes. Significantly higher levels of liver enzymes and inflammatory cytokines were found in the DCD group (P < .05). The release of liver enzymes peaked at 60 minutes and that of inflammatory cytokines peaked at 90 minutes. The hepatic sinusoidal space was wide at 90 minutes and narrowed after 120 minutes.ConclusionsThe results suggest that subnormothermic oxygenation perfusion may maintain optimal graft condition until around 90 minutes and perfusion for more than 120 minutes may be counterproductive.     

单纯钾停跳氧合血持续灌注不降温心脏直视手术(附160例报告)

应用钾停跳、氧合血持续灌注心肌保护、不降温体外循环行心脏直视手术１６０例，手术均顺利，术后无低心排综合征、无严重心律失常发生。全组死亡２例（１．２５％）。部分病例进行了ＬＤＨ１／ＬＤＨ２、ＣＫ－ＭＢ及血清乳酸测定，与低温体外循环组比较无统计学明显差异（Ｐ＞０．０５）。作者认为，此方法临床效果满意，值得进一步研究、推广应用。     

温氧合血心肌保护液临床应用26例

自1992年1月采用体外循环温氧合血心肌保护液连续灌注法，对26例各种心脏病患者进行了心内直视手术，自动复跳24例（92％），术后未见低心排综合征或严重心律紊乱，恢复顺利，作者认为，该法是一种安全，可靠的保护心肌方法，本文对温氧合血心肌保护液的配制和用量进行了探讨。     

Oxygenated Hypothermic Machine Perfusion of Kidney Transplantation from Donors After Cardiac Death Due to Long-Term Low Blood Pressure and Hypoxia: The First Case Report of a Clinical Trial Using a New Japanese Perfusion System

BackgroundMachine perfusion of marginal kidney grafts obtained from donors after cardiac death (DCD) has become a standard therapy worldwide. However, the use of grafts from DCD due to long-term low blood pressure is associated with a high incidence of primary graft nonfunction. Furthermore, the importance of oxygenation in machine perfusion remains unclear. We report the first case of a clinical trial of a kidney transplant obtained from a DCD using a Japanese oxygenated hypothermic perfusion system (CMX-08W, Chuo Seiko Co Ltd, Asahikawa, Japan).Patients and MethodsThe donor was a 61-year-old man with amyotrophic lateral sclerosis. His SpO₂ decreased to 80% to 90%, his blood pressure remained consistently low for 4 hours and 30 minutes, and he suffered a cardiac arrest. Subsequently, we carried him to the operating room. The warm ischemic time was 12 minutes, and the cold ischemic time was 418 minutes. The recipient was a 58-year-old man who had been undergoing hemodialysis for 26 years. He was diagnosed with nephrosclerosis and multiple renal cysts. Oxygenated hypothermic machine perfusion was used on the kidney transplant obtained from the DCD.ResultsThe recipient gradually recovered and was withdrawn from hemodialysis therapy 14 days post transplantation. His renal function improved, and he was discharged on postoperative day 36. Currently, his renal function remains good (phosphocreatine, 1.7).ConclusionsOxygenated machine perfusion is used to preserve organs and determine if an organ is suitable for transplantation. This may provide the possibility of perfusion preservation and expand the criteria for cardiac arrest-associated renal transplantation.     

Preservation techniques for heart transplantation: comparison of hypothermic storage and hypothermic perfusion

Preservation of the donor heart is an important and controversial subject in heart transplantation. This study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation (n = 14). The donor hearts of group A (n = 7) were placed in simple hypothermic storage for 5 hours. The donor hearts of group B (n = 7) were placed onto a perfusion apparatus for 5 hours, with pressure maintained at 28 cm of H2O and a myocardial temperature of 8 to 10 degrees C. In both groups the hearts were initially protected with isosmolar potassium cardioplegic solution. The perfusate in group B contained moderate sodium, mannitol, glucose, insulin, and oxygen. The ischemic interval within both groups was 6 hours including orthotopic transplantation. Investigation was conducted at three time periods: prepreservation, postpreservation, and immediately after loading. For both groups there was nonsignificant depression of myocardial function (cardiac index, stroke index, stroke work index, ejection fraction, and wall stress) at the postpreservation period. After volume loading, for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than 0.01; stroke index, p less than 0.01) with no significant change in heart rate, systemic vascular resistance, and systolic blood pressure. There was also significant improvement in myocardial performance (p less than 0.05) for the hypothermic perfusion group after volume loading. Ultrastructural changes were minimal for both groups, and there were no major heart transplantation after 6 hours of ischemia; however, hearts retain their contractile capacity better after hypothermic perfusion than after simple hypothermic storage.(ABSTRACT TRUNCATED AT 250 WORDS)     

巨大心脏瓣膜置换术的经验

目的 总结65例巨大心脏瓣膜疾病患者的瓣膜置换术的治疗经验。方法 巨大心脏瓣膜疾病患者65例,均在中度低温体外循环下进行手术,采用透析型人工肾超滤技术,心肌保护采用温氧合血停跳液诱导停搏及终末再灌注,4℃冷晶体间断灌注维持停搏技术。单纯二尖瓣置换术45例,均保留瓣下结构(MVR/SVP),主动脉瓣置换术7例,二尖瓣及主动脉瓣联合置换术13例,同时行三尖瓣Devega环缩术20例。结果 全组患者中54例心脏自动复跳,11例电击除颤复跳。3例死亡,2例出现顽固性低心排综合征死亡,1例因凝血功能障碍致创面广泛出血死亡,其余均治愈出院。结论 治疗经验:①充分术前准备;②采用超滤技术;③采用温氧合血停跳液诱导停搏及终末再灌注,4℃冷晶体间断灌注维持停搏心肌保护技术;④采用保留瓣下结构的二尖瓣置换术(MVR/SVP)。     

Effects of metabolic stimulation on cardiac allograft recovery

BACKGROUND: We previously demonstrated that continuous perfusion of cardiac allografts during hypothermic storage with donor blood harvested at the time of organ retrieval improves myocardial recovery after transplantation. However, myocardial metabolism and function remain depressed compared to base line values. This study evaluated the use of a continuous infusion of donor blood enhanced with insulin to augment aerobic myocardial metabolism during and after hypothermic storage. METHODS: Yorkshire pigs (45 to 50 kg) were used to perform 14 orthotopic cardiac transplants using either continuous perfusion with donor blood (blood group, n = 7) or perfusion with donor blood enhanced with 10 IU/L insulin (insulin group, n = 7). After heparinization, hypothermic (4 degrees C) cardioplegic arrest, and donor heart extraction, donor blood (2,844 +/- 210 mL) was harvested in both groups and perfused at room temperature (20 degrees C) at a pressure of 60 mm Hg for 3 hours. Blood cardioplegia was delivered after each anastomosis in both groups and arterial and coronary sinus blood samples were obtained to examine myocardial metabolism. A Millar micromanometer was used to measure left ventricular developed pressure and the rate-pressure product at varying preloads. RESULTS: There were no differences in either myocardial lactate or acid release between the two groups. Hearts in the insulin group displayed higher myocardial oxygen extraction than those in the blood group. The recovery of developed pressure was higher in the insulin group compared to the blood group (91% +/- 19% vs 73% +/- 2%, p = 0.04). CONCLUSIONS: In this model, continuous perfusion of cardiac allografts with donor blood and insulin preserves myocardial metabolism during hypothermic storage and improves metabolic and functional recovery after orthotopic cardiac transplantation.     

Effect of warm heart surgery on perioperative management of patients undergoing urgent cardiac surgery.

The anesthetic management and outcome data were examined in a retrospective case-controlled study that compared a conventional hypothermic cardioplegic technique with the recently described method of warm heart surgery, in patients undergoing urgent cardiac surgery. Hypothermic continuous oxygenated blood crystalloid cardioplegia with systemic hypothermia was used for 37 patients who underwent cardiac surgery by the same surgeon over a 16-month period from July 1986 (group 1), whereas normothermic continuous oxygenated blood crystalloid cardioplegia with systemic normothermia was used on 56 patients over the following 16-month period until March 1990 (group 2). The groups were similar in terms of age, sex, ASA status, NYHA classification, and preoperative left ventricular function. Defibrillation following cardiopulmonary bypass was required in only 3.6% of the warm heart surgery patients (group 2) compared with 83.8% in group 1 (P less than 0.0001), and use of warm heart surgery (group 2) eliminated the need for rewarming. There was a trend towards a reduced incidence of myocardial infarction (19% in group 1 vs 9% in group 2), low cardiac output syndrome (40% vs 29%), and use of the intraaortic balloon pump (16% vs 9%) in warm heart surgery patients, but these differences did not reach statistical significance. There were no differences between the two groups in terms of anesthetic drug usage, total heparin or protamine doses, blood loss, transfusion requirements, or duration of ICU stay.(ABSTRACT TRUNCATED AT 250 WORDS)