脑死亡动物模型的研究进展

脑死亡动物模型可用于研究器官移植供体的功能,大鼠、猪、狗、家兔、小鼠等是脑死亡动物模型常选用的模式动物.当前具有代表性的脑死亡建模方法,是通过急剧或缓慢颅内加压法建模,制备突发性脑死亡模型和渐进性脑死亡模型.模式动物脑死亡的判定目前尚无统一标准,现有脑死亡动物模型仍存在不足,不能全面模拟临床脑死亡,建模成功的判断与临床上脑死亡的诊断仍有差别.     

兔不同死因死后脑组织CT影像学变化的时间规律性研究

目的研究兔不同死因死后129h内脑组织CT影像学的变化规律与死亡时间的关系。方法分别采用机械性窒息、失血性休克和空气栓塞法,建立家兔死亡模型;在不同死后间隔时间对家兔进行颅脑薄层螺旋CT扫描,结合专业的计算机图像分析技术,监测脑组织面积/颅腔面积比、脑组织平均CT值、颅腔整体平均CT值等参数变化,并作统计学分析。结果脑组织平均CT值随着死亡时间的延长,呈先升高后降低。死后27h内,脑组织面积/颅腔面积比基本无变化;死后33h,脑组织面积/颅腔面积比、颅腔整体平均CT值随着死后间隔时间延长逐渐下降。建立了体现各项参数变化趋势的二项式回归方程(p0.001),具有显著的统计学意义。结论采用现代放射CT影像技术获得的不同死因死后颅脑组织的多参数的非线性回归方程,为法医学推断死亡时间提供了客观、准确的方法和参考依据。     

一种对血液动力学影响较小的判断犬脑死亡新方法

呼吸暂停试验在临床判定脑死亡诊断过程中起十分关键的作用。据报道,传统试验方法可引起严重低血压、肺动脉高压、心律失常等并发症。本研究在脑死亡动物模型中以吸入CO2提高PaCO2改进呼吸暂停试验,旨在减少对血流动力学的影响。结果表明,吸入CO2法能有效刺激呼吸中枢,与传统试验方法比较,能显著缩短试验时间,对血压、心率影响较小,试验过程中血管活性药物的需要量无显著增加。更重要的是未发现肺动脉高压。上述结果提示,吸入CO2法较传统方法更加安全,是一种可靠的呼吸暂停试验法。     

Intracranial causes of death and their mechanisms

Intracranial causes of death trail in incidence behind cardiovascular and respiratory system pathologies in most deaths occurring in hospitals. When intracranial pathology becomes more important is in the forensic arena, where it is often supposed that in troublesome cases such as sudden and unexpected deaths or where there appears to be no anatomic cause of death revealed in the general autopsy, the cause must be in the brain. This hope is often dashed after a careful neuropathological examination. Intracranial causes of death are discussed here mostly within the context of the forensic exercise where complex processes may be involved such as: electrophysiological dysfunctions; disorders of respiratory control; dysfunction of the intracranial pressure/volume equilibrium.     

心脏移植脑死亡供体的目标管理及心肌保护

背景：心脏移植是治疗终末期心力衰竭患者获得长期生存的有效方法。目的：探讨心脏移植脑死亡供体的管理和选择以及心肌保护作用。方法：通过数据库检索的方式对心脏移植脑死亡供体的管理和选择以及心肌细胞的保护研究进行分析。心脏移植的实施,需要有合格的供体器官。首先,要做好供体的管理和选择,其次,需要供体心肌保护和转运,减轻离体心脏缺血再灌注损伤。结果与结论：对于心脏移植脑死亡供体的管理,国家卫生部及相关部门制定标准和规范,使器官移植更加公开化、规范化、合法化,提高供心功能保护的效果,延长供体心脏的保存时间。心脏移植的全过程普遍应用低温停搏法,供心运输期间常用冷浸法保护心肌。随着脑死亡标准等相关规定的出台,供心保护的深入研究,边缘供体的拓宽,会使器官移植供体数量有所增加。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

The diagnosis of brain death

Physicians, health care workers, members of the clergy, and laypeople throughout the world have accepted fully that a person is dead when his or her brain is dead. Although the widespread use of mechanical ventilators and other advanced critical care services have transformed the course of terminal neurologic disorders. Vital functions can now be maintained artificially for a long period of time after the brain has ceased to function. There is a need to diagnose brain death with utmost accuracy and urgency because of an increased awareness amongst the masses for an early diagnosis of brain death and the requirements of organ retrieval for transplantation. Physicians need not be, or consult with, a neurologist or neurosurgeon in order to determine brain death. The purpose of this review article is to provide health care providers in India with requirements for determining brain death, increase knowledge amongst health care practitioners about the clinical evaluation of brain death, and reduce the potential for variations in brain death determination policies and practices amongst facilities and practitioners. Process for brain death certification has been discussed under the following: 1. Identification of history or physical examination findings that provide a clear etiology of brain dysfunction. 2. Exclusion of any condition that might confound the subsequent examination of cortical or brain stem function. 3. Performance of a complete neurological examination including the standard apnea test and 10 minute apnea test. 4. Assessment of brainstem reflexes. 5. Clinical observations compatible with the diagnosis of brain death. 6. Responsibilities of physicians. 7. Notify next of kin. 8. Interval observation period. 9. Repeat clinical assessment of brain stem reflexes. 10. Confirmatory testing as indicated. 11. Certification and brain death documentation.     

Apnea testing with continuous positive airway pressure for the diagnosis of brain death in a patient with poor baseline oxygenation status

Apnea testing is a key component in the clinical diagnosis of brain death. Patients with poor baseline oxygenation may not tolerate the standard 8-10 min apnea testing with oxygen insufflation through tracheal tube. No studies have assessed the safety and feasibility of other methods of oxygenation during apnea testing in these types of patients. Here, we safely performed apnea testing in a patient with baseline PaO₂ of 99.1 mm Hg at 100% oxygen. We used continuous positive airway pressure (CPAP) of 10 cm of H₂O and 100% oxygen at the flow rate of 12 L/min using the circle system of anesthesia machine. After 10 min of apnea testing, PaO₂ decreased to 75.7 mm Hg. There was a significant rise in PaCO₂ and fall in pH, but without hemodynamic instability, arrhythmias, or desaturation. Thus, the apnea test was declared positive. CPAP can be a valuable, feasible and safe means of oxygenation during apnea testing in patients with poor baseline oxygenation, thus avoiding the need for ancillary tests.     

Some aspects of ammonia formation in the brain of dying animals and during recovery after resuscitation

The dynamics of some indices of nitrogen metabolism in the brain was studied in dogs after lethal blood loss and in the postresuscitation period. The investigation showed that the main source of ammonia in the brain during the development of the organism and in the state of clinical death is glutamine. In the recovery period after resuscitation, however, glutamine becomes a remover of ammonia and the main source of ammonia becomes the labile amino groups of proteins.Department of Pathological Physiology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Negovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 686–688, June, 1977.     

Detached concern and death anxiety of first-year medical students: Before and after the gross anatomy course

The purpose of this study was to gather data from first-year medical students prior to their taking gross anatomy and again at the end of the course to determine if changes occur regarding death anxiety and detached concern toward patients. Chi-square and t-tests were used to assess statistical significance. From the 84 students for whom we had data both prior to and after gross anatomy, only the sociodemographic variable of sex was consistently related to the two dependent variables. Women reported more death anxiety prior to and after the gross anatomy course and were more likely to disagree with the need for detached concern. Clin. Anat. 10:201–207, 1997. © 1997 Wiley-Liss, Inc.     

临床脑死亡患者的脑电定性研究

目的:探讨脑电图(EEG)对脑死亡的诊断价值。方法:研究对象共35例,按照美同神经病学会(AAN)指南分成两组,脑死亡组和非脑死亡组。脑死亡组共有病人22例。其中男性14例,女性8例,年龄16～85岁;非脑死亡组13例,其中男性7例,女性6例,年龄17～84岁。使用床旁EEG机描记病人的脑电活动。2名专业医师进行脑电信号分析。结果:脑死亡组22例病人中,17例为脑电静息,占77%,临床均预后不佳;5例有脑电活动,占23%,其中4例在随访中有不同程度的恢复,1例死亡。非脑死亡组中无一例出现脑电静息,该组预后相对较好。结论:EEG是判定脑死亡一种重要的辅助检查方法。     

辣椒素诱导人骨肉瘤细胞MG-63发生免疫原性细胞死亡

目的探讨辣椒素与顺铂能否抑制人骨肉瘤细胞MG-63增殖并诱导其免疫原性死亡(ICD)。方法 MTT检测细胞的增殖;线粒体膜电位分析细胞凋亡;流式细胞计量术检测细胞膜上钙网蛋白(CRT)表达量;荧光素酶法检测细胞外ATP的释放;ELISA检测细胞上清中高迁移率族蛋白1(HMGB1)的分泌。结果辣椒素及顺铂作用均能抑制细胞MG-63增殖(P0.01),且呈剂量依赖性;辣椒素和顺铂均可诱导MG-63细胞凋亡(P0.01),但只有辣椒素能诱导MG-63细胞内质网中CRT转移到细胞膜表面,且促进ATP及HMGB1的释放(P0.01)。结论辣椒素可诱导人骨肉瘤细胞凋亡及免疫原性死亡。     

Donor brain death leads to differential immune activation in solid organs but does not accelerate ischaemia–reperfusion injury

A comparative analysis of inflammation between solid organs following donor brain death (BD) is still lacking and the detailed influence of BD accelerating ischaemia–reperfusion injury (IRI) post‐transplantation remains to be addressed. Applying a murine model of BD, we demonstrated that 4 h after BD organs were characterized by distinct inflammatory expression patterns. For instance, lipocalin 2 (LCN2), a marker of acute kidney injury, was selectively induced in BD livers but not in kidneys. BD further resulted in significantly reduced frequencies of CD3⁺CD4⁺, CD3⁺CD8⁺ T cells and NKp46⁺ NK cells in the liver, whereas BD kidneys and hearts were characterized by significantly lower frequencies of conventional dendritic cells (cDCs). Syngeneic models of kidney (KTx) and heart transplantation (HTx) illustrated stronger gene expression in engrafted BD hearts only, but 20 h post‐transplantation both organs displayed comparable intragraft lymphocyte frequencies, except for NK cells and graft function. Moreover, the complement factor C3d deposit detected in small vessels and capillaries in cardiac syngrafts did not significantly differ between BD and sham‐transplanted groups. Finally, no further influence of donor BD on graft survival was detected in an allogeneic heart transplantation setting (C57BL/6 grafts into BALB/c recipients). We show for the first time that BD organs are characterized by a varying inflammatory profile; however, BD does not accelerate IRI in syngeneic KTx and HTx. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Effect of delta sleep-inducing peptide on macromolecule biosynthesis in brain tissue of stressed rodents

For evaluation of the nature of adaptogenic properties of delta sleep-inducing peptide we studied the effect of this substance on macromolecule biosynthesis in the brain of rats and mice exposed to burn injury and psychoemotional stress, respectively. Anabolic activity of delta sleep-inducing peptide depended on the purpose of adaptation corresponding to the type of stress. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 400–403, April, 2006     

儿童心脏死亡器官捐献与肾脏移植1例报告

背景：器官短缺是全球移植界共同面临的难题,为扩大供者来源,缓解日益紧张的器官短缺,回避因脑死亡立法及诊断标准缺位造成的困惑,卫生部和中国红十字会联合推动心脏死亡器官捐献。 目的：探讨开展儿童心脏死亡器官捐献的可行性。  方法：回顾性分析解放军南京军区福州总医院1例儿童心脏死亡肾脏捐献案例,结合文献进行分析。  结果与结论：4岁男孩,心肺复苏后脑死亡,经过2次两组专家时隔24 h按脑死亡判定标准(儿童)和脑死亡判定技术规范,以及阿托品试验结果独立作出判定。捐献者父母对捐献方案知情同意,书面表达捐献意愿,且得到医院伦理委员会批准。按中国心脏死亡器官捐献工作指南逐步完成捐献申请、审批、转运、器官维护,以及生命支持治疗撤除、器官切取过程,热缺血时间13 min。按年龄、体质量和组织配型结果选择受者,2只肾脏分别植入2例尿毒症受者体内,左肾接受者为13岁女性,右肾接受者为35岁女性,术后未发生肾功能延迟恢复,无移植肾血管栓塞、尿瘘、输尿管梗阻等并发症。术后1年内移植肾由术前7 cm增大至10 cm,尿蛋白阴性,血肌酐≤60 μmol/L,估算肾小球滤过率70-150 mL/min。术后至今均未发生严重感染事件,血压正常,无糖尿病、高脂血症、肝功能损害等并发症,现生活自理,精神状态好,遵医行为佳。提示儿童心脏死亡器官捐献是过渡时期解决器官来源的方向之一。必须严格遵守患者救治利益高于一切的基本原则,积极探索儿童心脏死亡器官捐献规范化操作程序。     

Complement biosynthesis by mononuclear phagocytes

Mononuclear phagocytes are an important in vivo source of a wide range of complement components. They are able to rapidly up-regulate or down-regulate complement synthesis in response to many different pharmacological and biological stimuli. This ability is likely to make a significant contribution to maintaining host defences particularly in peripheral tissues. The important role of molecular biology in the study of complement biosynthesis by mononuclear phagocytes will be emphasised.     

Complement-mediated inflammation and injury in brain dead organ donors

The importance of the complement system in renal ischemia-reperfusion injury and acute rejection is widely recognized, however its contribution to the pathogenesis of tissue damage in the donor remains underexposed. Brain-dead (BD) organ donors are still the primary source of organs for transplantation. Brain death is characterized by hemodynamic changes, hormonal dysregulation, and immunological activation. Recently, the complement system has been shown to be involved. In BD organ donors, complement is activated systemically and locally and is an important mediator of inflammation and graft injury. Furthermore, complement activation can be used as a clinical marker for the prediction of graft function after transplantation. Experimental models of BD have shown that inhibition of the complement cascade is a successful method to reduce inflammation and injury of donor grafts, thereby improving graft function and survival after transplantation. Consequently, complement-targeted therapeutics in BD organ donors form a new opportunity to improve organ quality for transplantation. Future studies should further elucidate the mechanism responsible for complement activation in BD organ donors.