【作者】 齐向北；

【导师】 张英泽； 潘进社；

【作者基本信息】 河北医科大学 ， 外科学， 2009， 博士

【摘要】 第一部分99Tcm -SZ-51对兔骨水泥髓腔灌注后肺血栓形成及其干预措施的放射免疫显像研究骨水泥(Polymethyl Methacrylate,PMMA)是一种医用黏合、支持材料,因其操作简便、固定可靠、不易松动,并且是骨质疏松患者假体植入的首选黏合材料,因此被广泛应用于人工关节置换术,但在应用过程中,有些患者突然发生血压下降、呼吸困难等一系列不良反应。目前认为这些不良反应是由于插入股骨假体时栓子进入血循环引起肺栓塞所致,栓子的确切成份尚无定论,目前认为可能是血凝块、脂肪滴、骨屑或骨水泥颗粒等。活化血小板单克隆抗体SZ-51为针对人α颗粒糖膜蛋白(granule membrane glycoprotein ,GMP-140)的单克隆抗体,且不与血循环中静止的血小板反应,只与活化的血小板反应,活化血小板是构成新鲜血栓的主要成分之一,这种单抗是由苏州医学院血栓与止血研究室发明,主要用于在体血栓的放射免疫学动态检测,已广泛地应用于动物实验,被证明是一种检测在体新鲜血栓的有效方法。99Tcm标记抗人活化血小板单抗SZ-51血栓放射免疫显像(radio-immuno-image,RII)用于诊断周围血栓的实验研究和临床应用已有报道,经证实它能与犬、兔活化血小板发生特异性结合,为它作为血栓显像示踪剂提供了理论依据。本实验应用99Tcm - SZ-51作为血栓标记物,运用放射免疫显像技术观察兔骨水泥髓腔灌注后及不同方法干预后,肺部血栓的变化情况,并探讨预防肺栓塞发生的干预措施。目的:应用99Tcm -SZ-51检测骨水泥灌注后兔肺血栓的形成,并探讨预防肺栓塞发生的干预措施。方法:大耳白兔16只,体重2.5-3.0kg,随机分为4组,每组4只,第一组(未干预组):骨髓腔灌注骨水泥并加压,第二组(盐酸肾上腺素组):骨髓腔内用盐酸肾上腺素盐水(1:10000)冲洗髓腔后灌注骨水泥并加压,第三组(生物蛋白胶组):用生物蛋白胶喷洒骨髓腔后灌注骨水泥并加压,第四组(空白对照组):骨髓腔中不灌注骨水泥。每组动物手术切除股骨头、扩髓,在骨水泥灌注前耳缘静脉注入99Tcm -SZ-51 2ml,骨水泥灌注后60mins,120mins和180mins进行核素显像,测定活体肺放射活性,之后立即处死动物,完整取出肺组织,测定离体肺放射活性,测定结束后肺组织固定进行病理学检测,观察肺部血栓及相关病理改变。结果:骨水泥髓腔灌注并加压后分别于60mins、120mins和180mins检测各组放射活性,第一组分别为11.48±2.35、14.41±3.10和18.25±5.01,第二组分别为8.21±3.21、10.19±2.40和11.32±3.12,第三组分别为4.06±1.04、5.68±2.80和7.40±1.12,各时间点组间统计学分析差异有显著性(P<0.05)。病理学检测肺部有血栓形成,骨水泥髓腔灌注前应用盐酸肾上腺素或生物蛋白胶处理骨髓腔后,肺部放射活性明显下降,但仍高于空白对照组。结论:99Tcm -SZ-51可以用于骨水泥灌注后兔肺血栓形成的动态观察。应用盐酸肾上腺素和生物蛋白胶可以降低骨水泥肺栓塞的发生率。第二部分多种干预措施预处理骨髓腔预防骨水泥植入综合征的动物实验研究在骨水泥型髋关节置换术中脂肪栓塞的发生率为0.1%,这个并发症最早于1970年被报道。Charnley于20世纪50年代首次在人体关节置换中应用骨水泥。后来,在骨水泥型关节置换术中,研究人员逐步报道了一些严重的并发症,包括血压下降、心跳骤停、深静脉血栓形成、肺栓塞等,统称为骨水泥植入综合征。文献报道髋关节置换术中、术后肺脂肪栓塞的发生率约为0.1%。骨水泥植入综合征中,动脉血压下降最为常见。Smith等对3482例骨水泥型全髋置换术进行了统计,结果血压下降10mmHg以内者占83 %, 10-20mmHg者占11 %,超过20mmHg者占6.7 %。本实验对术中使用多种干预措施预处理骨髓腔预防骨水泥植入综合征的发生进行了探讨。目的:探讨兔髋关节置换术中扩髓后肾上腺素盐水、股骨扩髓区域钻孔及纤维蛋白医用胶(FS胶)对髓腔预处理及其联合应用对术中骨水泥植入综合征的预防作用。方法:(1)采用2×2×2析因实验设计,将欲行单髋关节置换术的48只比利时兔随机分成8组。(2)分别给予扩髓后肾上腺素盐水冲洗髓腔(盐酸肾上腺素组)、股骨扩髓区域钻孔(钻孔组)、纤维蛋白医用胶喷涂髓腔(FS胶组)以及上述干预措施联合应用处理骨髓腔。使用BL-420E+生物机能实验系统实时监测各组家兔外周动脉压、中心静脉压、心率、呼吸频率的变化,收集数据并作统计学分析。夹闭气管处死家兔后取下肺脏送病理检验,高倍镜观察微栓子。结果:(1)FS胶组、肾上腺素冲洗+钻孔+ FS胶三种方法联合应用组血压下降幅度减少;(2)肾上腺素盐水组、FS胶组、肾上腺素盐水+FS胶联合应用组、FS胶+钻孔联合应用组、肾上腺素冲洗+钻孔+ FS胶三种方法联合应用组血压下降持续时间减少。结论:(1)肾上腺素盐水冲洗,FS胶及其肾上腺素盐水+FS胶联合应用、FS胶+钻孔联合应用、肾上腺素盐水+钻孔联合应用、肾上腺素冲洗+钻孔+ FS胶联合应用对骨水泥致血压下降有预防作用;(2)钻孔对血压下降无预防作用,但对肾上腺素盐水冲洗,FS胶处理有协同作用。第三部分盐酸肾上腺素在骨水泥型髋关节置换术中预防骨水泥植入综合征的临床研究骨水泥属于丙烯酸类化合物(Acrylics),它的主要化学成分为聚甲基丙烯酸甲脂( Polymethyl methacrylate,PMMA),其聚合时容易成型,固化后坚固,可将假体牢固地固定于骨组织上,但它并非为真正的粘合剂,仅在假体与骨之间起到填充锚固作用。在骨水泥型髋关节置换术中,研究人员逐步报道了一些严重的并发症,包括血压下降、心跳骤停、深静脉血栓形成、肺栓塞等,统称为骨水泥植入综合征。目前认为这些不良反应是由于插入股骨假体时栓子进入血循环引起肺栓塞所造成的,栓子可能是血凝块儿、脂肪滴、骨屑、空气或骨水泥颗粒等。有研究发现在人工髋关节置换过程中,通过检测右心室射血分数和经食道动态心动图发现,当插入股骨假体时,右心室的血液动力学都会发生改变,并且经食道动态心电图发现,右心室内有异常物质通过,但是多数患者并无临床表现,仅少数重症患者发生死亡,通过肺灌注扫描和尸检都证实了肺栓塞的存在。与骨水泥相关的关节置换术死亡率的报道不尽相同,国外报道骨水泥肺栓塞的死亡率是0.05%,国内报道2.3 %~2.4 % ,我院统计914例髋、膝关节骨水泥假体置换术患者,4例死亡,死亡率为0.44%。本实验通过研究骨水泥对血液动力学影响以及盐酸肾上腺素在骨水泥型髋关节置换术中的临床应用,探讨预防骨水泥植入综合征的有效措施。目的:探讨骨水泥对血液动力学影响以及盐酸肾上腺素在骨水泥型髋关节置换术中预防骨水泥植入综合征的临床应用。方法:回顾分析了2008年7月至2009年4月期间,我们实施的骨水泥型髋关节置换术共48例(其中骨水泥植入前未用盐酸肾上腺素盐水冲洗髓腔--未干预组24例,骨水泥植入前用盐酸肾上腺素盐水冲洗髓腔--干预组24例)。比较两组患者骨水泥植入前和植入后1、2、3、4、5、6、7、8、9、10min的收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、心律(HR)、血氧饱和度(SPO2)的数据变化,数据结果采集后用方差分析和Q检验进行统计学处理。结果:未干预组:所有病例都有不同程度血压下降,骨水泥植入1min,血压开始下降,2-6min血压下降最为显著(SBP ,DBP,p<0.01),7min开始回升(SBP, p>0.05;DBP, p<0.05),10min恢复正常;血氧饱和度下降明显(p<0.05),心率无明显变化,无统计学意义(p>0.05)。干预组:骨水泥植入前用1:500000肾上腺素盐水冲洗髓腔后,用浸有肾上腺素盐水(1:500000)的纱布填塞髓腔,骨水泥灌注前、后各时间点SBP、DBP、MAP、HR、SPO2均无明显变化,p>0.05,无统计学意义。结论:未干预组24例患者都有不同程度的血压下降,血氧饱和度下降,骨水泥植入后2-6min对血液动力学影响显著;干预组中1例血压轻度下降,1例出现偶发室性早搏,余22例血液动力学无明显改变。由此可见,肾上腺素盐水冲洗髓腔能有效地预防骨水泥植入综合征的发生。第四部分髋关节置换术后早期康复训练对高龄患者降低肺栓塞发生率及其功能恢复的影响人工髋关节置换术(hip arthroplasty, HA)是通过手术利用人工生物材料替代与重建病损的髋关节,以缓解症状、消除疼痛、改善及恢复髋关节功能、提高生活质量为目的的一种治疗手段。主要适用于髋关节骨性关节炎、髋关节类风湿性关节炎、股骨头缺血性坏死III - IV期或股骨头严重变形、先天性髋臼发育不良、先天性髋脱位、继发性骨性关节炎、年龄在55岁以上的老年人股骨头粉碎性骨折或头下型股骨颈骨折等。近几年随着我国人均寿命延长,对生活质量要求提高,因髋部疾患需行髋关节置换术的高龄患者日益增多。髋关节置换术引起的功能改变也越来越受到重视。及时、安全、有效地进行功能恢复训练,可降低术后肺栓塞的发生率,提高患者的生活质量。髋关节置换术后康复锻炼在功能恢复和减少并发症方面起着重要作用,可影响手术治疗效果。如果术后卧床时间较长,未能及早进行康复治疗,患者可能出现不同程度的肌力减退及关节挛缩,下肢出现血液淤滞,流速减慢,极易形成深静脉血栓,造成肺栓塞,将严重影响髋关节功能的恢复及手术的疗效,甚至造成死亡。如何对行髋关节置换手术的患者进行早期的康复训练指导,有效缓解术后疼痛、提高肢体功能状态、缩短康复时间、改善患者总体生存质量,防止肺栓塞发生是临床医护工作者和广大患者所共同关心的问题。髋关节置换术后并发的深部静脉血栓是一种严重威胁机体健康的术后并发症。对深部静脉血栓的早期诊断,及时防治可减少致命性肺栓塞和远期下肢深静脉功能不全的发生率。本实验拟研究高龄患者髋关节置换术后早期康复锻炼对手术治疗效果和降低肺栓塞发病率的影响。目的:探讨髋关节置换术后早期康复训练对高龄患者降低肺栓塞发生率及其功能恢复的影响。方法:共95名患者符合研究标准,男63例,女32例;其中新鲜股骨颈骨折62例,股骨颈骨折内固定术后股骨头坏死21例,原发性股骨头坏死12例。患者按年龄分为两组:高龄组(≥80岁)34名,非高龄组(<80岁)61名。术前发给每位患者一本指导手册,主要向患者介绍术后的康复训练方法,指导患者术后的康复训练。并于术前和术后6个月时采用WOMAC量表对入选患者进行功能评定。术后6个月时采用SF-36量表进行生存质量评定。结果:所有患者没有一例发生肺栓塞。WOMAC评分两组患者疼痛、功能、僵硬均有显著改善。除高龄组患者术后6个月时僵硬程度较大,差异有统计学意义外,余差异均无统计学意义。SF- 36评分两组患者在疼痛缓解、功能恢复、生活质量均有明显改善,两组差异无统计学意义。结论:髋关节置换术后早期康复训练能降低高龄患者肺栓塞的发生率,有助于功能恢复,年龄不是影响髋关节置换术后效果的决定因素。更多还原

【Abstract】 Part 1 Radioimmunoimaging of bone cement pulmonary artery thrombi in rabbits with 99Tcm -SZ-51 and intervention studyBone cement (Polymethyl Methacrylate, PMMA) is a medical bonding, support materials, because of its simplicity, regularity and reliability, fastness. It is the preferred bonding material as prosthesis implantation for osteoporosis patients. It was widely used in artificial joint replacement. However, in the process of application, adverse reactions occurred in some patients, such as drop of blood pressure, dyspnea . Currently some people believed that the emboli getting into the blood circulation led to pulmonary embolism,when the femoral prosthesis was inserted into the bone marrow cavity.The exact composition of emboli was unclear, and it may include the blood clot, fat droplets, bone chip or bone cement particles, etc.Platelet activating monoclonal antibody SZ-51, can not combine with the unactivated platelets, but combined with the activated platelet. Activated platelets are the main component of thrombus. SZ-51 is from Suzhou Medical College Thrombosis and Hemostasis Institute, and mainly used in vivo thrombosis immunology dynamic radiation detection. It has been widely used in animal experiments. It has been proved to be an effective detection method in fresh thrombosis.99Tcm - SZ-51, a marker of thrombosis, was used in this study through Radioimmunoimaging technology. The change of radioactivity of 99Tcm - SZ-51was measured under different pretreatments and the preventive intervention for bone cement implantation syndrome was investigated in this study.Objective: To detect pulmonary artery thrombosis with 99Tcm SZ-51 after a rabbit cement perfusion, and to discuss the ways of preventing pulmonary artery thrombus.Methods: Sixteen rabbits (weight 2.5-3.0 kg)were randomly divided into 4 groups, the group A (no intervention group): bone cement perfusion into madullary cavity and compression, the group B(adrenalin hydrochloride group), pretreat the madullary cavity with adrenalin hydrochloride (1:10000), and then bone cement perfusion and compression, the group C (fibrin sealant group), pretreat the madullary cavity with fibrin sealant, and then bone cement perfusion and compression, the group D (blank control group), no bone cement perfusion. The femur head of each animal was removed and the femur was reamed. 99Tcm -SZ-51 was injected through ear marginal vein into each rabbit before bone cement perfusion. The radioactivity was measured at 60,120 and 180min. The radioactivity of lung was measured in vivo. The lung was harvested and it’s radioactivity was measured in vitro. The pathological examination has been done.Results: The radioactivity of each group was measured at 60, 120 and 180 min The radioactivities are 11.48±2.35, 14.41±3.10, 18.25±5.01 ID/pixels in the group A, 8.21±3.21、10.19±2.40, 11.32±3.12 ID/pixels in the group B,4.06±1.04, 5.68±2.80, 7.40±1.12 ID/pixels in the group C. The difference among groups is statistically significant (P<0.05). Pulmonary artery thrombus had been found in group A, B and C, not ingroup D. Pretreatment with adrenalin hydrochloride and fibrin sealant, the radioactivity of lung was significantly decreased.Conclusion: 99Tcm-SZ-51 could be used in the observation of pulmonary artery thrombus formation after bone cement perfusion in rabbit. Pretreatment with adrenalin hydrochloride and fibrin sealant before bone cement perfusion can significantly lower the risk of pulmonary artery thrombus. Part2 The experimental study of different pretreatments to prevent bone cement implantation syndrome in hip arthroplasty.The incidence of fat embolism was 0.1% in bone cemnet hip arthroplasty . This complication was first reported in 1970 . In the 1950’s, Charnley was the first man who used the bone cement in human arthroplasty. Later, in the bone cement hip arthroplasty, the researchers reported some progressively serious complications, including drop of blood pressure, cardiac arrest, deep vein thrombosis, pulmonary embolism, and they were collectively called as bone cement implantation syndrome. The serious fat embolism of lung was often observed in or after the bone cement hip arthroplasty. It was reported that the postoperative incidence of pulmonary embolism is about 0.1% in the hip replacement. The drop of blood pressure was more often observed in bone cement implantation syndrome. Smith, observing 3482 cases of bone cement total hip replacement for the statistics, found that the drop of blood pressure below 10mmHg accounted for 83%, 10-20mmHg for 11%, more than 20mmHg for 6.7%. In this experiment,we want to investigate possible methods to prevent the adverse effect of BCIS during hip arthroplasty by the rabbit model.Objective: To investigate possible methods to prevent the adverse effect of BCIS during hip arthroplasty by the rabbit model.Methods: 48 Belgium rabbits of either sex, 1.8-2.4 kg body weight, were anaesthetized with intravenous pentobarbitone sodium (10mg/kg body weight) and anaesthesia was maintained by additional doses of pentobarbitone sodium. The 48 Belgium rabbits(48 hips) were assigned to 8 groups randomly. The control group consisted of 6 rabbits, treated with conventional cementing technique; group 1-7 pretreated the medullary cavity with adrenaline(1:10000), drilling holes in femur,Fibrin Sealant or combined with these factors before having cement and femoral prosthesis inserted. Arterial blood pressure, central venous pressure and respiration rate were recorded at the carotid artery, the external jugular vein and the tracheal cannula by BL-420E+biological functional experimental system respectively. Data was collected and analyzed with SPSS. Specimens was taken from each lobe of the lung. The tissue sections were observed.Results: The blood pressure drop in group 3,4,7 are more significant than that in the control group, and the duration of blood pressure drop was shorter in group 1,3,5,6,7. Conclusions: Adrenaline saline, fibrin sealant and combined use of adrenaline and fibrin sealant, combined use of fibrin sealant and drilling holes, combined use of adrenaline and drilling holes can prevent blood pressure dropping during the HA;drilling holes have no effect,but can played a synergistic role with fibrin sealant.Part 3 Clinical Study Of Epinephrine Hydrochloride Prevents Bone Cement Implantation Syndrome In The Bone Cement Hip ReplacementBone cement belongs to Acrylic compounds. Its main chemical ingredients was Polymethyl methacrylate(PMMA). It is easy to shape, strong. It can be used to firmly fix prosthesis on the bone. However, it is not the real adhesives, only plays a role of filling fixed between the prosthesis and bone. in the bone cement hip arthroplasty, the researchers reported some progressively serious complications, including decreased blood pressure, cardiac arrest, deep vein thrombosis, pulmonary embolism, collectively called as bone cement implantation syndrome . Currently some people believe that the emboli get into the blood circulation leading to pulmonary embolism,when the femoral prosthesis was put into the bone marrow cavity.The exact composition of emboli can not be determined, may be the blood clot, fat droplets, bone chip or bone cement particles, etc. It was reported that the right ventricular hemodynamic changes can be observed by detecting right ventricular ejection fraction and something that passing through right ventricular be detected by dynamic transesophageal echocardiography during the hip replacement process, but no clinical manifestations in most patients, only a small number of patients died. The existence of a pulmonary embolism can be confirmed by the pulmonary perfusion scan and autopsy. Mortality in bone cement arthroplasty was reported differently. In foreign reports, the mortality rate of pulmonary embolism of bone cement was 0.05%, Internal report, 2.3% ~ 2.4%. About 914 cases in our hospital, the hip joint, knee joint bone cement replacement patients,4 cases of death, mortality rate was 0.44%.In this experiment,we want to investigate the bone cement influence on hemodynamics and the clinical application of Epinephrine hydrochloride to prevent bone cement implantation syndrome in the bone cement hip replacement.Objective: To investigate the bone cement influence on hemodynamics and the clinical application of Epinephrine hydrochloride to prevent bone cement implantation syndrome in the bone cement hip replacement.Method: In this study, we analysed retrospectively 48 hip replacement patients from July 2008 to April 2009. All the patients were divided into two groups; no intervention group, 24 patients--no preparation of bone marrow cavity with saline epinephrine hydrochloride before implantation of bone cement;intervention group, pretreatment bone marrow cavity with saline epinephrine hydrochloride before implantation of bone cement. Systolic blood pressure (SBP), diastolic blood pressure (DBP), the mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SPO2) were compared between two groups before and after bone cement implantation 1,2,3,4,5,6,7,8,9,10 min. The data were analyzed with variance and Q test.Results: Drop of blood pressure was observed for all patients in no-intervention group starting at 1min after bone cement implantation and the most significant blood pressure drop occurred at 2-6 min. the blood pressure was geting back at 7 min (SBP, p>0.05; DBP, p<0.05)and back to normal around 10min; oxygen saturation was decreased significantly (p<0.05). No statistical difference were found on heart rate,. In the intervention group, bone marrow cavity was pretreated with saline epinephrine hydrochloride before implantation of bone cement. Gauze baptisted with saline epinephrine hydrochloride (1:500000) were packed in the medullary cavity. No significant difference were found on the SBP, DBP, MAP, HR, SPO2 at different time points before and after bone cement implantation (p> 0.05).Conclusion: There was the most significant change of hemodynamics around 2-6 min in no-intervention group. In the intervention group, one patient was found with blood pressure drop and another one with the occasional premature ventricular contractions. Pretreatment of marrow cavity with saline epinephrine hydrochloride can effectively prevent bone cement implantation syndrome.Part 4 Effect of Early Postoperative Rehabilitation on pulmonary embolism and function recovery of aged Hip Arthroplasty PatientsThe biological materials was uesed to replace the and reconstruct the lesion hip joint to alleviate the symptoms in Hip Arthroplasty(HA). The purpose of a treatment is elimination of pain, improvement and restoration of hip joint function, improving the quality of life. It is suitable to hip osteoarthritis, rheumatoid arthritis of hip joint, avascular necrosis of femoral head III - IV or severe deformation of the femoral head, congenital acetabular dysplasia, congenital hip dislocation, of secondary bone arthritis, the age of the elderly over the age of 55 comminuted fractures of the femoral head or neck. In recent years, with improvement of people’s quality of life, hip arthroplasty in elderly patients is increasing. Timely, safe and effective for functional recovery training, can reduce the incidence of postoperative pulmonary embolism and improve the quality of life of patients.Doing exercise after operation in the functional recovery and reduce complications play an important role, it can influence the effect of surgical treatment. If a longer time in bed after surgery, failed to carry out rehabilitation treatment as soon as possible, the degrees of muscle be reduced and the patient occur joint contracture, lower limb blood stasis, flow down easily to form deep vein thrombosis, resulting in pulmonary embolism, would seriously the impact to hip joint function and surgical efficacy, and even death. It is clinical workers and patients’common concern that how to prevent pulmonary embolism by early rehabilitation training after hip replacement surgery.The deep vein thrombosis is a life-threatening post-operative complication. The early diagnosis, timely prevention and treatment of deep vein thrombosis can reduce fatal pulmonary embolism. This study will show that how to prevent bone cement implantation syndrome and improve the joint function after hip replacement surgery for aged patients by early rehabilitation training.Objective: To evaluate the significantly lower the risk of pulmonary artery thrombus and effect of early rehabilitation program on aged people who underwent hip arthroplasty.Methods: 95 patients who received primary hip arthroplasty were evaluated immediately prior to surgery and 6 months postoperatively. Pain, function, and health related quality of life were evaluated with the WOMAC and the SF-36.each patient was given a guide-book describing the hospitalization period and the postoperative exercise program preoperatively.Results: None of the patients were found pulmonary embolism postoperatively. There were no age-related differences in joint pain, function, or quality-of-life measures preoperatively or 6 months postoperatively. Patients, regardless of age, showed significant improvement in pain, function, and stiffness. That was no significant difference between the 2 age groups regarding the preoperative and 6-month postoperative scores, except the older group reported less hip stiffness at 6 months. The magnitude of change as depicted by effect sizes typically showed greater gains in pain than function or stiffness for both age groups.Conclusions: Early postoperative rehabilitation program on hip arthroplasty for aged patient can significantly lower the risk of pulmonary artery thrombus.With increasing improvement of surgical technique and early rehabilitation program, age alone is not a factor that affects the outcome of hip joint arthroplasty and should not be a limiting factor when considering who should receive this surgery.更多还原