【作者】 胡辉莹；

【导师】 钟世镇；

【作者基本信息】 南方医科大学 ， 人体解剖与组织胚胎学， 2008， 博士

【摘要】 一、研究背景及目的猝死在我国的发生率每年大约有60万人。猝死的抢救成功率极低,即使在发达国家,猝死的病人只有5%—15%可以到达医院,而其中只有1%—20%的病人经抢救能够存活。抢救心脏骤停的患者,每延迟一分钟做心肺复苏(Cardiopulmonary Resuscitation,CPR),其存活率即下降7%-10%。心肺复苏在世界医学领域内所受关注的程度正在逐年上升,现代心肺复苏技术经过近50年的发展,形成了如今国际通用的三级九步法。三级即是心肺复苏的三个基本程序:①基础生命支持(basic life support,BLS);②高级生命支持(advanced life support,ALS);③持续生命支持(prolonged life support,PLS)。BLS是整个复苏过程的基础和关键,而胸外按压(external chest compression,ECC)又是BLS中的重要环节,2005国际最新心肺复苏指南特别强调了有效不间断胸外按压的意义。有关胸外按压的频率问题、胸外按压的效果以及胸外按压确切机理等问题一直是CPR学术界关注的焦点:(1)胸外按压频率由早年推荐的60次/分钟,增加到最新要求的100次/分钟,近年来有学者提出了高频按压(120次/min以上)的观点,是否频率越高越好呢?(2)胸外按压的有效性问题:最新心肺复苏指南对胸外按压的部位、力度、下压的深度有了明确的规定,并强调按压应有力而快速:按压部位要求在两乳头之间,按压幅度为4～5cm,婴儿为胸廓的1/3～1/2;每次按压后胸廓完全弹回,保证松开的时间与按下基本相同。然而有临床研究显示:临床胸外按压过程中,近50%的胸外按压不合格:一半的胸外按压幅度太浅,而且CPR过程中24%～49%的时间里未进行胸外按压。按压时,允许胸壁弹性回缩能够增加回心血量,而胸壁复位不充分时,回心血量减少导致心排血量降低;过多中断按压,冠脉和脑血流中断,复苏成功率明显降低。(3)胸外按压的机制问题:最早提出的是心泵机制学说,即认为有节律地按压胸骨可使胸骨与脊柱间的心脏被挤压,关闭房室瓣使心室内压增高,推动血流向前;按压解除时,心室恢复舒张状态产生吸引作用,使血流充盈心脏,反复按压推动血液流动而建立人工循环。20世纪80年代,学者们开始从血流机制方面对CPR机制进行探讨,提出了胸泵机制学说,即心肺复苏时胸外按压使心脏复跳的机制是通过胸腔压力的变化而使血流流动。近年来,国内有作者提出胸腔-大血管-心脏之间的“共振频率”效应学说,究竟哪种学说是胸外按压时血流向前的主要机制?以上三个与临床紧密结合的问题的研究,目前在临床上存在观察例数少、缺乏对比实验、病例选择受限、影响因素较多等限制,较难得出科学的结论。心肺复苏传统研究方法有:动物模型研究、临床研究和人体模型研究。能否找到一种研究方法,既可以对胸外按压的效果作更深入的探讨,还可以进一步研究传统认可的“心泵”、“胸泵”机制和推论的“共振”机制,甚至发现新的胸外按压机制?本研究通过人体标本的生物力学试验,测试出人体胸外按压时作用力与胸廓位移及应变的关系;利用生物力学三维有限元建模的方法,在计算机上重建正常人体胸廓三维有限元模型,并对模型进行有效性检验后,应用有限元分析方法模拟分析外力作用下胸廓的应力及应变分布。本方法避免了以往心肺复苏研究的局限性,首次应用生物力学的研究方法分析心肺复苏胸外按压时按压力度、频率与形变关系等胸外按压的关键技术问题,为CPR的基础研究开辟了一个新的探讨领域。二、材料与方法1.胸外按压的解剖学基础:了解人体胸廓、胸壁,以及心脏的解剖结构。2.人体胸廓胸外按压的生物力学测试试验:选择1具男性新鲜尸体标本,实验前摄片以排除胸廓原有疾病(包括骨折,畸形等)的存在。应用解放军第458医院157临床部双排螺旋CT对其进行胸部扫描。采用已知重力0-200牛顿(Newt,N),分别模拟人体胸外按压时胸廓所承受的负重工况,使用MTS材料试验机和引伸仪,测试垂直加压情况下人体胸廓的位移和应变。本实验分为A、B两组。A组是在具有完整胸部的标本上完成试验;B组是在A组试验完成后,剔除标本胸壁的肌肉和软组织以及胸腔脏器后进行试验。测试方法设计为静态垂直加压和动态加压;静态垂直加压方法指设定加载范围为0-200 N,实施分级加载,每级为50 N。试验机的加载速度为5.0mm/S。动态加压方法指模拟临床胸外按压条件,设置频率为100次/分钟、施加载荷的时间与胸廓放松时间相等(0.3s)的情况下,测试胸廓按压点在不同外力作用下的位移。A、B两组试验位移的测量点相同:按压点(第7测量点)—胸骨体前正中线第4、5肋间;第6测量点—左侧第5肋距前正中线38.0mm;第5测量点—左侧第4肋距前正中线42.0mm;第4测量点—左侧第3肋距前正中线37.6mm;第3测量点—左侧第2肋距前正中线28.7mm;第2测量点—前正中线第3肋水平面的交界点;第1测量点—前正中线第2肋水平面的交界点。3.构建人体胸廓三维模型:选择与前试验同1例的男性新鲜尸体进行螺旋CT扫描,扫描范围:第一胸椎上缘至第十二肋骨下缘进行连续螺旋扫描,选择骨组织窗的CT影像窗位为396,窗宽为1536。扫描层厚1.0mm,扫描时间为36.53 s,共获取人体胸廓二维图像440层,图像以DICOM格式存贮。将二维DICOM格式的图像导入Mimics10.1软件,确定图像空间方位后,对图像进行分割,建立了包括脊柱、胸骨和肋骨的人体骨性胸廓三维模型。4.人体胸廓三维有限元模型的建立:在Mimics10.1软件中,将人体胸廓进行表面网格划分并进行优化后将模型以Ansys Element Files(.lis)的格式导入ANSYS9.0软件中进行体网格划分,并保存胸廓体网格模型文件返回导入Mimics10.1软件。在Mimics10.1的有限元分析模块中,利用软件自带的“CT图像灰度-组织力学材料性质”关系公式,对三维胸廓体网格模型的各单元进行材质分配。材质分配完成后的体网格模型再次返回导入ANSYS9.0软件中进一步优化,如此多次反复、优化后得出完整人体胸廓有限元网格模型。5.人体胸廓三维有限元模型的有效性检验:将前期生物力学测试的结果与已经建立的胸廓有限元模型进行对照,比较相同作用力下两组的位移、应变关系,通过两组数据的趋势曲线来检验模型的有效性。6.人体胸廓胸外按压的有限元分析:将证实有效的人体胸廓三维有限元模型进行垂直方向模拟按压加载,约束边界条件后进行求解运算,分析压力为0-400N时人体胸廓有限元模型各部位的位移、应力和应变分布,结合临床进行结果分析。三、结果1.人体胸廓具有一定的弹性和活动性,胸廓各骨通过肋椎关节、肋横突关节、胸肋关节相互连接,当胸外按压时,垂直向下的力量作用于胸骨,再通过胸骨与肋骨的连接、肋骨和肋椎关节等使胸廓的矢状径和横径发生变化。肋软骨富于弹性,在抢救呼吸骤停的病人时,可进行体外心脏按压或人工呼吸。人体胸外按压时按压的部位即心脏与胸廓最为接近的位置。2.人体胸廓标本的生物力学测试显示:(1)静态垂直加压时,由A组和B组的力-位移关系曲线可知:①压力由0～200 N变化时,位移呈现压力依赖关系,即随着压力的增加,胸廓各测量点的位移也随之增加。②压力相同时,不同测量点的位移不同,按压点(7点)的位移最大,依次是7点＞6点＞5点＞2点＞4点＞1点＞3点。③从A组的压力-位移关系曲线上看到,胸廓下移达到40mm距离的只有按压点在受到200N的载荷力时才能实现。④A、B两组比较:同力作用下B组位移更大,当外力为200N时,B组按压点位移达到60mm,观察发现标本的胸骨和肋骨未发生骨折。(2)动态加压时胸廓的压力-位移关系曲线结果:当模拟临床胸外按压频率为100次/分钟、按压与放松时间相等时测量到的外力与位移的关系从趋势线上得知,位移随着外力的增加而增大。(3)从动态和静态加压时位移的柱形图可知:相同测量点的动态位移明显小于静态位移。根据力-应变关系曲线,当外力作用于胸廓时,应变呈现压力依赖关系,即随着外力的增大,各测量点的应变也增大。3.建立了包含1158 085个节点、736 022个单元的计算机人体胸廓三维有限元模型,此模型完整地重现了人体胸廓的复杂形态,得到了包括锁骨、肋骨、脊柱等结构鲜明、直观、整体的可计算模型图像。4.由于完整胸廓的单元和网格数据偏大,而且考虑到第11、12浮肋与前胸廓不相连,对胸廓运动的影响不大可忽略等因素,计算前减去第11肋以下部分,得到包含356 562个节点、215 808个单元的胸廓模型。通过比较生物力学测试试验与所建立模型在相同力作用下的位移和应变,我们发现,首次建立的模型在外力作用下的位移与力学测试的位移差别较大,重新调整模型的材料性质后将模型与力学测试再次进行比较,最后得出较为合理的胸廓可计算模型。5.胸廓有限元模型分析结果:正常人体胸廓施加压力后的应力分布均匀,呈对称性分布。按压胸廓时,胸廓的应变集中部位与应力集中部位不同,前者多位于胸骨、肋骨交界处,后者多位于肋骨约束自由度处;即变形程度最大的部位在按压部位的胸骨、肋骨交界处,而受力的集中部位在背部。四、结论1.人体胸腔内心脏与胸廓最接近的位置与胸外按压的位置几乎相同,此结构特征是“心泵机制”理论的解剖基础。胸廓是一个由多种骨和骨连接组成的复杂结构,胸外按压时,垂直向下的力量作用于胸骨,再通过胸骨与肋骨的连接、肋骨、肋椎关节等使胸廓的矢状径和横径发生变化,胸腔内压增大,这是“胸泵机制”理论中胸腔压力变化的解剖学基础。2.胸外按压时,在相同力作用下,按压点的位移最大;距离按压点位置越近,位移越大;在同一肋骨水平,位于胸骨的测量点较肋骨测量点的位移大。按压胸廓时,按压力度越大,胸廓的变形也越大,由此推论胸腔压力的改变也会随之增加。3.在同力按压时,完整胸腔的下压位移小于骨性胸廓的下压位移,由于下压点位置正好是心脏与胸骨接触面最大、最密切的位置,心脏的相反作用力可使按压时的动能减少导致位移减小,从而推论:胸外按压时心脏的形变是存在的。4.模拟人体胸外按压频率的生物力学动态测试试验得知作用力与位移的关系曲线并得出结论:随着按压力的增加,位移逐渐加大;从曲线的趋势公式:Y=8.0173X+38.698(Y为作用力,X为位移)得知:当位移达到40mm时,施加的外力是359.39N(相当于37公斤),其胸廓的位移与静态测试人体标本以及有限元模型计算出的位移比较都明显减少。根据实验结果可以推论,使胸廓下压40mm需要达到至少300N(相当于31公斤)的按压力量,频率越高,需要的下压力量也越大。按压力量的大致明确对于我们今后的胸外按压实际操作具有重大的意义。5.本研究成功建立了人体胸廓三维有限元模型,此模型的建立在生物力学有限元研究领域和急救医学领域均属创新。6.本研究将建立的人体胸廓有限元模型进行了有效性检验,将修正后的模型计算结果与生物力学测试数据进行对照,在相同外力作用下,两组的位移曲线趋势一致,应变曲线趋势也一致而且极为接近,由此我们认为本模型有效,并且能为我们今后的临床研究提供有意义的有限元分析数据。7.从胸廓有限元模型应力、应变的分析结果得知,胸外按压时应变的集中部位在胸骨、肋骨交界处(即肋软骨处),而各个肋软骨的应力和应变最大部位在第4肋软骨和第5肋软骨处;从人体标本生物力学测试的位移变化来看,各个肋软骨位移变化由大到小依次为:第5肋软骨＞第4肋软骨＞第3肋软骨＞第2肋软骨;结合人体胸廓解剖结构可以推论:第5肋软骨是临床按压时最容易发生骨折的部位,胸外按压的部位确定在第4肋间隙与胸骨的交界处较为合理。8.本研究不足之处和未来展望。本研究在建立人体胸廓有限元模型时所涉及的生物材料力学特性均假定为均质、连续和各向同性,然而实物材料本身并不是均质、连续的,也不是各向同性,而是呈各向异性的特征。对于这种状况,绝大多数有关骨骼的有限元分析模型都是存在的,这也是该方法本身固有的缺陷。人体胸廓具有胸肋关节、肋椎关节、和肋横突关节,然而本研究建立的胸廓模型不具有以上关节,特别是胸肋关节的缺失,在一定程度上影响了胸廓位移的变化。以往有限元有关骨骼的研究多为静态情况下的局部分析,然而胸外按压是一个动态进行的过程,由于人体胸廓有限元模型数据偏大和有限元分析软件功能的限制,本实验目前还未能在胸廓有限元模型上动态分析有关作用力与位移、频率与胸腔容积改变的关系,以及利用有限元模型进行胸廓固有频率的计算,预计在不远的将来,随着有限元分析技术的不断完善,我们的研究会不断地完善,此模型也能更好地为临床服务。本研究建立的人体胸廓有限元模型的分析和应用,不仅局限在急救复苏的研究领域,还可以用于其他人体胸廓生物力学相关问题的研究,其应用范围很广,可重复性强。此模型的分析可以设计为相关分析软件作进一步的推广和应用,具有一定的社会效益和经济效益。通过研究胸外按压时作用力与位移的关系,为我们今后人体胸外按压的临床研究打下良好的基础。更多还原

【Abstract】 Background and objectivesIncidence of sudden death approximates up to 60 million each year in China. However,the patients who can get to hospital for rescue are only 5%-15%,and only 1%-20%of them can survive.In case of sudden heart arrest,if cardiopulmonary resuscitation（CPR） is postponed one minute,the survival rate is reduced by 10%-7%. So world medical domain pays close attention to CPR year by year.After almost 50 years,modern CPR has developed into three levels of nine steps.The three levels include:①Basic Life Support（BLS）.②Advanced Life Support（ALS）.③Prolonged Life Support（PLS）.BLS is basis and key to entire resuscitation and the external chest compression（ECC） is an important procedure in BLS.The theory of CPR has been developing constantly from the last century to this day.In 2005,the newest international CPR guideline especially emphasized the effectiveness and continuity of ECC.The concerns that CPR academic circles show include always its frequency,definite mechanism and effect.（1） The frequency of ECC has increased from previous 60 times/min to current 100 times/min.In recent years,some scholars suggested high frequency compression（above 120 times/min）.（2） The validity of ECC:The newest CPR guideline clearly regulated the compression depth,location and strength.In order to be effective,the compression must be quick and forceful. The location of compression is between two mammilla,the palm should maintain correct position after compression,and compression should extend for 4～5cm for adults and 1/3～1/2 of thorax for babies.The thorax must be completely resilient,and relaxing time should be basically equal to pressing time.However,some clinical studies display:50%of ECC is unqualified,for the extent of ECC is insufficient, moreover,24%～49%of the time is not devoted to ECC process in CPR.Chest wall elastic recover is able to increase the returned blood volume.If chest wall does not recover,the reduction of the returned blood volume will induce cardiac output loss. Accordingly,too much discontinuance compression will lead to aeteria coronaria and cerebral blood flow discontinuance,and the success ratio of CPR is obviously reduced.The mechanism of ECC is also a focal point of resuscitation development. The mechanism of cardiac pump was first suggested that regular compression extrudes the heart between breastbone and backbone so that the pressure in heart ventricle increases and blood marches.When the pressure relieved,heart ventricle revives for suction effect and blood come back to heart.Eventually,the artificial circulation is established through recompression.In 1980’s,scholars begin to study the mechanism of CPR in blood flow,and proposed the theory of thorax pump.Some researchers proposed the theory of resonance frequency between thorax,great vessels and heart.Traditional research methods of resuscitation include animal model, clinical research,and human model.Empirical study of ECC is limited by time, environment and different anatomic structure of different species,so the use of the research method is also limited.Through the vitodynamic experiment of body samples,however,the present research tested stress and straining of thorax during ECC.The finite element model of human thorax was re-established to reflect the practical problems reasonably,clearly and accurately.After testing the availability of the model,the present research utilized finite element analysis to investigate the stresses and deformations during the ECC process,providing biomechanic evidence and new thinking for addressing the mechanisms and clinic effects of CPR.Materials and Methods1.Anatomical foundation of ECC:The anatomical structures of human thorax,chest wall, as well as the provisional location of heart and thorax were studied systematically.2.Biomechanical tests of ECC upon the human thorax:One case of fresh male cadaver specimen was selected and its chest radiography was taken before the experiment to exclude any disease（including fractures,deformity,etc） that may exist. The chest was scanned by double spiral CT in the 157th Clinical Department of the 458^th People’s Liberation Army Hospital.The conditions of withstanding different loads during human thorax compression were simulated respectively,by use of MTS testing machine and extension device.The thorax displacement and strain were tested under the vertical compression of a known gravity 0-200 N（Newton）.This study enrolled two groups:groups A and B.The tests were performed on the entire and intact chest in group A,but after the soft tissues in the chest wall and the whole organs inside the cavitas thoracis were removed in group B.The points of experimental displacement measurement were the same.The seven pressing points were at the anterior midline of the sternum and between the intercostal 4^th to 5^th(7^th point),from the left rib section 5 before the midline 38.0mm(6^th point),left rib section 4 from the center line before being 42.0mm（5th point）,from the left rib section 3 before the midline 37.6mm(4^th point),from the left rib section 2 before midline 28.7mm(3^rd point),before the midline of the horizontal section 3 rib junction point(2^nd point),and the center line and the junction point of the horizontal ribbed(1^st point).3.Constructed the 3D model of human thorax:The spiral CT images of the same cadaver specimen in the last experiment were selected（biomechanical tests completed）.Spiral CT scan was conducted continuously from the first to the upper edge of the 12^th rib margin,bone tissue fault observation windows were chosen to observe the thorax and reconstruction of the skeleton.The window level was 396 and window width 1536. The slice thickness of scan was 1.0mm,and scan time was 36.53 s.A total of 440 two-dimensional images of human thorax were obtained,and the images were stored in DICOM format.The two-dimensional images in DICOM format were imported into Mimics10.1 software.A 3D model of spine,stemum and rib bone of thoracic was established by Mimics10.1 software after spatial orientation of images and the image segmentation were performed.4.Constructed the 3D finite element model of human thorax:The 3D images of thorax were modified and surface-meshed with the software of Mimics 10.1.The model was discriminated into six kinds of material.Then the model of surface-meshed could be kept as the document ANSYS named.lis as the suffix and be introduced into ANSYS software directly to establish a 3D finite element model.5.Validity test of 3D finite element model of human thorax:The results of biomechanic tests and 3D finite element model of thorax were compared,and the two sets of bias and straining under the same force were compared.At last,the validity of 3D finite element model was tested by the tendency of the two sets of data.6.The finite element analysis of ECC upon the human thorax:The 3D finite element models of human thorax which had been confirmed effective were subjected to perpendicular loading in simulation.The bias,stresses,and straining of the models were analyzed during perpendicular loadings of 0-400N,then the results were analyzed in comparison with clinical data.Results1.All the bones of the thorax are connected with costovertebral joints, costotransverse joints and stemocostal joints.Thorax is flexible and active.When ECC is performed,the vertical compression force impacts on sternum,then the articulation of the sternum and ribs,ribs and costovertebral joints,so that the sagittal and transverse diameters of thorax change.Because the rib cartilage is rich in elasticity,the external cardiac compression or artificial breathing is preferred for the patients who suffer from sudden breath arrest.The locations of ECC points are nearly identical to the closest positions of heart to the thorax.2.Biomechanical tests on the thorax samples of fresh adult male showed that the displacements and straining of human body samples thorax were as follows:（1）Under the static compression,the results of strength-offset relation were:①The offset displayed pressure-dependent relationship when loading changed from 0 from 200 N. The offset increased at every measurement point while loading increased.②When the external force was identical,the offset varied with measurement points.The offset at the 7^th pressing point was maximal.The proper order was:offset at pressing point 7＞at point 6＞at point 5＞at point 2＞at point 4＞at point 1＞at point 3.③The pressing point moved down 40mm in depth only when it accepted the loading force of 200 N.④The comparison between groups A and B:The offset in Group B was bigger under the same force.When the external force was 200N,the offset at the pressing point reached 60 mms,but the sternum and rib of the sample did not fracture.（2） Under dynamic compression,the relations between loading and displacement of thorax were shown as follows.When the clinical chest compression at a frequency of 100se/min was simulated and the relaxing equaled the compression in time,the tendency line between external force and straining showed that the displacement offset was enlarged as soon as the external force increased.（3）The column diagram of displacements between the dynamic and static states demonstrated that the displacement in the dynamic state at the same measurement point is much smaller than that in the static state.According to relation curve of force-strain,when the external force acted on the thorax,straining was shown to be pressure-dependent.As the external force（loading） increased,the strain at every measurement point increased.3.The three-dimensional finite element model was built with 1158 085 nodes and 736 022 elements,imitating complicated structures of human thorax,including clavicle,rib,and vertebral column.The model could display distinctly and directly the entire images of structure of human thorax which could be used in calculation.4.Since the entire thorax elements and net lattice data were too numerous,and the 11^th and 12^th floating ribs could be ignored,a model of 356 562 nodes and 215 808 elements was created by subtracting the part below the 11^th rib before calculation. Comparing the offset and strain between the biomechanic tests group and the model group under identical force effects,we found that the offsets between the original model and the biomechanic tests group were greatly different.After the model material was adjusted,the model was compared and verified with the former experiment group once again before the reasonable thorax model was calculated.5.The analyses of the thorax finite element model showed that the stresses distributed homogeneously and symmetrically after the loading was exerted on normal thorax. The concentrated location of straining on thorax was different from that of stress when compression acted on the thorax.The former was located in the border of sternum and rib,and the latter in the rib where the degree of freedom was restrained. The maximal deformation during compressing was located in the border of sternum and the rib,while the straining was located in the back at the same time.The present research compared the stress with the strain of every rib.Conclusions1.The heart will be deformed obviously,and the deformation increases as the external chest compression becomes more forceful.The anatomic features of heart and chest bone support the theory of cardiac pump and mechanism.The thorax is a complicated structure consisting of many bones and synostoses.During ECC,a vertical downward force affects chest bone,and changes the sagittal and the transverse diameters through the sternum and rib connections,ribs,thoracic vertebral joints.The intrathoracic pressure becomes greater consequently.This is the anatomical basis of thoracic pump mechanism.2.Under the same force,the nearer the palpating point,the larger the bias.In the same rib,the bias at the measuring point of sternum is larger than that at the measurement point of rib.Thoracic deformation is in direct ratio to the force during ECC.3.The heart deformation occurs definitely during ECC.4.The biomechanical tests show that in the dynamic circumstances,the bias is to increase with force.The trend line of relation between the force and bias shows the following force and displacement formula:y=8.0173x+38.698.It will offer momentous reference data for quantifying the effect of ECC.5.The three-dimensional finite element model of human thorax is established successfully on the computer.6.Under the same external force,the tropism of bias in the human thoracic 3D finite element model and that in the biomechanic tests group are consistent.The tropism of straining curve is consistent in the two groups too.Thus,we think that this model is effective and provides meaningful finite element analysis data for our future clinical studies.7.The biomechanic experimental results show that the fifth costicartilage is likely to get fractured during clinical compression.It is reasonable that ECC should be conducted on the quartus spatium intercostale. 8.One weakness of this study is that all the biomaterials are supposed to be homogenous,continuous and isotropic.But that is different from the fact.Another weakness is that the thorax of the body has the following links:articulationes stemocostales,articulatio costovertebralis,and articulatio costotransversaria,but the model does not.The absence of articulationes sternocostales matters especially, because it can influence the change of bias.The finite-element method and method of biomaterial tests of the specimen have its own advantages and disadvantages.The two methods should supplement each other so that results obtained can be more scientific and reasonable.更多还原