心肌内心电图Tslew诊断大鼠急性排斥反应的可靠性

目的 评估心肌内心电图(IMEG)心室起搏(VER)的T波后支斜率(Tslew)用于诊断大鼠异体心脏移植术后急性排斥反应的可靠性.方法 建立改良Ono大鼠腹部异位心脏移植动物模型,对照组(同基因移植)10只,实验组(异基因移植)30只.在供心右室流出道、左室游离壁和左室心尖部的心肌处分别埋置心表起搏电极,用两根导线作为起搏电极,描记VER,测Tslew.对照组术后第7天、实验组分别在术后3、5、7天处死,移植心脏作病理活检.结果 术后3、5、7天各时点,对照组Tslew差异无统计学意义,实验组呈进行性下降,术后3～5天、3～7天之间两两差异有统计学意义(P＜0.05);两组间比较第5、7天差异有统计学意义(P＜0.05),实验组Tslew变化与病理相关(P＜0.05);Tslew的ROC曲线下面积为0.9474,95%可信区间(0.8753～1. 0000);在最佳分割点(≤90%)灵敏度94.74%,特异度81.82%,阳性预测值和阴性预测值、符合率90%.Tslew≤92%为阳性分割点,灵敏度100%,特异度63.64%;≤85%作为阳性分割点,特异度90.91%,灵敏度78.95%.结论 Tslew是诊断大鼠心脏移植术后急性排斥反应的可靠指标;在最佳分割点,Tslew具有良好的诊断价值,缺乏心内膜活检条件时可以作为替代或补充;在适当分割点,Tslew可以作为急性排斥反应筛选的敏感指标.

Abstract：

Objective This study aimed to evaluate the reliability of Tslew in survelliance of allograft rejection after heart transplantations in rats. Methods Forty rats underwent modified Ono's heterotopic heart transplantation. The autonomous IMEG and VER were recorded with epicardiac pacing leads fixed at right ventricular outflow tracts, left ventricular apex and free wall. Tslews were detected daily in these 10 syngeneic and 30 allogeneic transplants. Syngeneic transplants were sacrificed on 7th postoperative day and allogeneic transplants were sacrificed on 3rd, 5th and 7th postoperative days, respectively.Histopathologic studies were performed at the same time. Results On the 3rd ,5th and 7th postoperative days Tslews depressed gradually in the allogeneic group. The depressions between 3rd and 5th, 3rd and 7th were obvious( P ＜0.05 ). No significant differences were observed in the syngeneic group. Tslews differed between the two groups at 5th and 7th postoperative days ( P ＜0.05 ). The Depression correlated with histopathologic results. Area under ROC( receiver operating characteristic) curve (AUC) of Tslew was 0.9474 and the 95% confidence interval(CI) was (0. 8753 -1. 0000 ). At the cutoff point of 92% ( ≤92% considered positive), Tslew had a sensitivity (Se) 100%, specificity (Sp) 63.64%, positive predictive value (PV + )82.61%, negative predictive value (PV-) 100%, respectively. At the cutoff point 85%, Sp 90.91%, Se 78.95%, PV +93.75 %, PV- 71. 43%. At the best cutoff point 90%, Tslew had a Se 94.74%, Sp 81. 82%, PV + 82.61%, PV- 90%.Whereas QRS had a Se 68.42%, Sp 90.91%, PV + 92.86%, PV- 62.50% at the best cutoff point of 72.3%. Conclusion Tslew of VER are reliable indexs to monitor acute allograft rejection after heart transplantations in rats. Having great diagnostic value, Tslew may be used as a replacement for EMB at the best cutoff point when EMB can' t be performed. At cutoff point of 92%, Tslew may be used as a screening index.     

抗体介导的排斥反应所致的移植心脏组织病理学变化的观察

目的 研究心脏移植术后移植心中抗体介导的排斥反应(AMR)的发生情况及其组织病理学特征.方法 2003年1月至2007年12月接受心脏移植的受者10例.术后受者移植心功能异常时,以及术后1个月、3个月、1年、2年和3年时进行移植心心内膜心肌活检(EMB),共取得17份活检组织样本,进行常规病理学和C4d免疫组织化学染色.依据2004年国际心脏和肺移植学会(ISHLT)的病理学诊断体系以及移植心AMR诊断体系进行病理学诊断.C4d免疫组织化学染色结果以0至+++予以分级.结果 10例17次EMB中,1次样本不合格,余16次EMB中,7例次诊断为C4d阳性AMR,3例4次诊断为急性细胞性排斥反应,2例次诊断为Quilty损伤.7例次AMR中,1例合并急性细胞性排斥反应,余6例次均为单独发生.10例受者中,1例移植后20个月死亡,尸体解剖检查诊断为慢性排斥反应合并AMR和急性细胞性排斥反应(ISHLT分级3级).其移植心AMR组织学特征为局灶性至广泛性心肌间毛细血管内皮C4d阳性沉积.结论 AMR是心脏移植术后主要的并发症之一,EMB及其C4d免疫组织化学染色是早期诊断AMR的有效方法.     

心内膜心肌活检监测移植心脏排斥反应——附213例次心内膜活检结果分析

目的 探讨原位心脏移植术后心内膜心肌活检(EMB)的必要性和安全性.方法 62例心脏病患者接受原位心脏移植,采用两剂巴利昔单抗诱导,环孢素A、霉酚酸酯(或硫唑嘌呤)及泼尼松维持免疫抑制治疗.术后3周、3～4个月、5～6个月、12个月常规进行EMB,对发生无法解释的心率明显变化、新出现的心律失常或心功能下降者加作EMB,每次于右室室间隔的不同部位夹取5～7块心肌组织.按照国际心肺移植协会的病理分级标准进行分级.取材后进行心电图、超声心动图检查,并摄X线胸片,以判断EMB后并发症.结果 随访(18.0±7.0)个月,58例(93.5%)存活,共行213例次EMB,10例次(4.7%)诊断为排斥反应Ⅲ级,19例次(8.9%)为Ⅱ级,184例次(86.4%)为0+Ⅰ级.临床怀疑排斥反应者12例次,加做EMB,4例次(33.3%)诊断为排斥反应Ⅲ级,8例次(66.7%)为0+Ⅰ级.EMB后,2例次(0.9%)发生三尖瓣返流,但未见右心功能不全;2例(0.9%)出现一过性完全性右束支传导阻滞.结论 即使是使用高效免疫抑制剂的今天,EMB仍是监测心脏移植后排斥反应的必要和安全的方法.     

移植心脏病理学诊断标准及其进展

随着心脏移植外科技术的提高和强效免疫抑制剂的临床应用,心脏移植例数和移植心脏存活时间均显著提升。然而在心脏移植术后的不同阶段,仍然可出现移植心脏右心室衰竭、缺血- 再灌注损伤、急性排斥反应、“Quilty病变”、感染和以移植心脏冠状动脉血管病（TCAD）为特征的慢性排斥反应等一系列并发症。心内膜心肌活组织检查（EMB）技术的应用使得包括排斥反应在内的移植心脏多种并发症的病理学特征得以观察和掌握,并成为移植心脏并发症最为准确的诊断手段。本文对移植心脏病理学研究的简史、心脏移植术后主要并发症及其诊断标准以及移植心脏排斥反应诊断研究的最新进展进行阐述,旨在使更多的心脏移植受者受益。     

多层螺旋CT与MRI联合应用对隐匿性骨折及骨挫伤的诊断价值

目的在隐匿性骨折及骨挫伤的诊断过程中联合应用多层螺旋CT以及MRI(核磁共振成像)进行辅助诊断,探讨并评价其应用价值。方法对于2016年3月至2018年3月在本院行多层螺旋CT以及MRI检查的100例隐匿性骨折及骨挫伤患者的检查影像资料进行回顾性分析,对两种检查结果的准确性进行对比。结果采用MRI诊断检查隐匿性骨折的准确率为91%、Se(灵敏度)为94.74%、Sp(特异度)为80%,PV+(阳性预测值)为98.90%、PV-(阴性预测值)为44.44%,采用多层螺旋CT诊断检查隐匿性骨折的准确率为97%、Se为98.97%、Sp为66.67%,PV+为98.97%、PV-为66.67%;采用MRI诊断检查骨挫伤的98%,Se(灵敏度)为98.97%、Sp(特异度)为50%,PV+(阳性预测值)为98.97%、PV-(阴性预测值)为50%,采用多层螺旋CT诊断检查骨挫伤的准确率为88%,Se(灵敏度)为93.26%、Sp(特异度)为54.55%,PV+(阳性预测值)为94.32%、PV-(阴性预测值)为50%。结论在隐匿性骨折的诊断中,多层螺旋CT要优于MRI,而在骨挫伤的诊断中,MRI要优于多层螺旋CT,故在进行检查时,要根据患者的意愿以及诊断要求进行多层螺旋CT以及MRI联合应用,提高患者的治疗依从性以及准确诊断概率。     

纤维支气管镜肺活检在准确诊断肺移植术后急性排斥反应中的作用

目的 探讨肺移植术后纤维支气管镜肺活检(TBLB)对准确诊断急性排斥反应(AR)的作用.方法 分析肺移植术后有完整TBLB随访资料的50例受者AR的诊断情况.肺移植术后50例受者常规进行TBLB共145例次.根据术后早期TBLB的病理学诊断结果,将受者分为早期AR组和早期无AR组.分析术后早期TBLB诊断AR的阳性率,术后远期两组受者AR发生率和TBLB对诊断AR的准确率.结果 术后早期受者AR发生率为44%(22/50).早期AR组22例受者中,经TBLB诊断为AR的共有25例次;TBLB对肺移植术后早期AR的诊断准确率为100%.受者术后远期AR发生率为22%(11/50),其中早期AR组和早期无AR组分别有5例和6例受者发生AR.TBLB对术后远期AR的诊断准确率为100%.所有发生AR的受者中,有61.1%的受者无典型的AR临床表现.结论 肺移植术后急性排斥反应无典型的临床表现,容易误诊,TBLB对诊断肺移植术后急性排斥反应具有较高的准确率.     

纤维支气管镜肺活检在准确诊断肺移植术后急性排斥反应中的作用

目的 探讨肺移植术后纤维支气管镜肺活检(TBLB)对准确诊断急性排斥反应(AR)的作用.方法 分析肺移植术后有完整TBLB随访资料的50例受者AR的诊断情况.肺移植术后50例受者常规进行TBLB共145例次.根据术后早期TBLB的病理学诊断结果,将受者分为早期AR组和早期无AR组.分析术后早期TBLB诊断AR的阳性率,术后远期两组受者AR发生率和TBLB对诊断AR的准确率.结果 术后早期受者AR发生率为44%(22/50).早期AR组22例受者中,经TBLB诊断为AR的共有25例次;TBLB对肺移植术后早期AR的诊断准确率为100%.受者术后远期AR发生率为22%(11/50),其中早期AR组和早期无AR组分别有5例和6例受者发生AR.TBLB对术后远期AR的诊断准确率为100%.所有发生AR的受者中,有61.1%的受者无典型的AR临床表现.结论 肺移植术后急性排斥反应无典型的临床表现,容易误诊,TBLB对诊断肺移植术后急性排斥反应具有较高的准确率.     

纤维支气管镜肺活检在准确诊断肺移植术后急性排斥反应中的作用

目的 探讨肺移植术后纤维支气管镜肺活检(TBLB)对准确诊断急性排斥反应(AR)的作用.方法 分析肺移植术后有完整TBLB随访资料的50例受者AR的诊断情况.肺移植术后50例受者常规进行TBLB共145例次.根据术后早期TBLB的病理学诊断结果,将受者分为早期AR组和早期无AR组.分析术后早期TBLB诊断AR的阳性率,术后远期两组受者AR发生率和TBLB对诊断AR的准确率.结果 术后早期受者AR发生率为44%(22/50).早期AR组22例受者中,经TBLB诊断为AR的共有25例次;TBLB对肺移植术后早期AR的诊断准确率为100%.受者术后远期AR发生率为22%(11/50),其中早期AR组和早期无AR组分别有5例和6例受者发生AR.TBLB对术后远期AR的诊断准确率为100%.所有发生AR的受者中,有61.1%的受者无典型的AR临床表现.结论 肺移植术后急性排斥反应无典型的临床表现,容易误诊,TBLB对诊断肺移植术后急性排斥反应具有较高的准确率.     

心肌内心电图在心脏移植体液排斥反应中的变化

心肌内心电图(IMEG)已经被证实是一项无创、安全、简便易行的监测心脏移植急性排斥反应的方法.本实验旨在观察IMEG于体液排斥反应发生时的变化. 一、资料与方法 以雄性杂种犬为实验对象,供体体重在10 kg左右,受体体重为20 kg左右.     

心脏移植术后急性排斥反应1例临床监测经验总结

目的 总结心脏移植术后急性排斥反应的临床监测体会.方法 回顾性分析1例心脏移植术后死于急性排斥反应患者的临床资料,分析术后排斥反应监测情况.结果 患者术后半年随访行心内膜心肌活组织检查(活检),结果为Ⅱ级急性排斥反应,经治疗好转出院.术后3年因上呼吸道感染出现气促再次入院,心内膜心肌活检结果为0~ⅠA级改变,病情恶化,...     

Clinical heart transplantation without routine endomyocardial biopsy.

In a prospective clinical study, routine endomyocardial biopsy (EMB) for early detection of cardiac allograft rejection was replaced by two noninvasive diagnostic techniques. In 32 patients who underwent transplantation during a 6-month period, intramyocardial electrogram (IMEG) amplitude was recorded with the telemetry function of a dual-chamber pacemaker system. An amplitude decrease of more than 8% below the individual range of variability in overnight long-term recordings served as an indicator of rejection. A prolongation of the time interval Te--the time span between maximal posterior wall contraction and peak retraction velocity--of more than 20 msec was used as an additional indicator of rejection-related left ventricular dysfunction. For patient safety, routine EMBs were still performed but remained undisclosed to the transplantation team. The pathologist was asked to intervene in cases of discrepancies between biopsy results and medical decisions, but no such intervention was necessary. Twenty-seven rejection episodes were treated medically, of which 22 were diagnosed noninvasively. In four patients, EMB, ordered because noninvasive parameters remained inconclusive, led to medical treatment. No false negative IMEG results were observed. Retrospective correlation with rejection gave a 100% negative predictive value for IMEG and a 96.9% negative predictive value for echocardiographic diagnosis. We conclude that omission of a schedule of routine biopsies is justified, if the described techniques of IMEG and echocardiography are meticulously applied and indicate normal cardiac function. EMB remains indicated if noninvasive parameters are not conclusive or if false-positive IMEG results, which were observed in the presence of infection or arrhythmias, are suspected. The frequency of EMB can be reduced by 90%, compared to conventional routine biopsy schedules. Diagnostic safety is increased because the additional information gained from IMEG and echocardiography is helpful in the interpretation of EMBs.     

心肌内心电图监测和诊断大鼠心脏移植术后的排斥反应

目的寻找监测和诊断心脏移植术后排斥反应的敏感心电指标。方法建立40只改良Ono法大鼠腹部异位心脏移植模型，其中对照组（同基因大鼠心脏移植）10只，实验组（异基因大鼠心脏移植）30只。在心脏移植术中，于供心右室流出道的心肌处缝置一单极的心表起搏导线，描记心肌内心电图，测量QRS波波幅和心率。对照组大鼠在术后第7天处死，实验组分别在术后3、5、7d处死，取移植心组织进行病理检查。结果对照组大鼠的ORS波波幅在手术2d后趋于稳定，术后3、5、7d各时点间的ORS波波幅差异不显著；实验组大鼠术后ORS波波幅呈进行性下降，术后3、5、7d各时点间比较，其波幅的降低幅度差异有统计学意义。对照组和实验组大鼠术后心率变化无明显规律，两组间比较，差异无统计学意义。心肌组织病理检查显示排斥反应的分级与ORS波波幅下降有明显的相关性。结论心肌内心电图描记是监测和诊断心脏移植术后排斥反应的有效方法，ORS波波幅是诊断和监测排斥反应发生的敏感指标，严重排斥反应发生时ORS波波幅明显下降。心率的变化不是监测心脏排斥反应的可靠指标。     

Intramyocardial electrogram recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.

OBJECTIVE: The purpose of this study was to prove the reliability of intramyocardial electrogram (IMEG) recordings for diagnosis and treatment monitoring of (1) cellular and (2) humoral mediated allograft rejection after heart transplantation. MATERIAL AND METHODS: Fifteen beagle dogs underwent heterotopic neck-heart transplantation. Eight of them were previously sensitized through several skin transplantations. IMEG recordings were performed daily. Donor-specific antibodies (IgG, IgM) were determinated in serum daily. Transmyocardial biopsies were performed every two days. RESULTS: In the sensitized group (group I) accelerated rejection occurred under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone on the fifth postoperative day (range: 4th-5th). All episodes were detected through IMEG diagnosis. In each case rejection could be treated successfully. In the cellular mediated group (group II), the average sensitivity for rejection diagnosis of a single lead was 24% for the unipolar and 42% for the bipolar leads. When the voltages of different leads were summed up the sensitivity rose to 36% (3 unipolar), 81% (3 bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 hours. CONCLUSION: The IMEG detects cellular and humoral mediated rejection early and with high reliability. The rejection-related changes of grade 2/3a rejection in IMEG seem to follow a Ofocal patternO similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance diagnostic reliability.     

Utility of biochemical markers in the follow-up of heart transplant recipients

Endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. However, considering the potential complications of this procedure, a noninvasive marker of rejection would be an ideal alternative or at least a helpful adjunct to posttransplant management. We measured myoglobin (Myo), creatine kinase MB mass (CK-MBm), troponin T (cTnT), serum amyloid A (SAA), and C-reactive protein (CRP) in 57 patients (mean age 37.5 years) who underwent orthotopic heart transplantation for end-stage cardiac failure between January and December 2001.Endomyocardial biopsies were performed routinely after surgery and histologically diagnosed rejection was graded according to the criteria of the International Society of Heart and Lung Transplantation. Concomittant with the biopsies, blood samples were drawn from the coronary sinus (central blood samples) and from a peripheral vein (peripheral blood samples) to assay biochemical markers. Among 149 EMB evaluated, 87 were negative (grade 0); 28 showed grade 1a rejection; 26 showed grade 1b; and 8 showed grade > 1b (2 were grade 2, 6 were grade 3a). Grades 0 and 1a were considered to be negative, while grades 1b and >1b were considered positive indicating potential acute graft rejection. cTnT, Myo, CK-MBm, SAA, and CRP levels were measured in 149 central blood samples and 149 peripheral blood samples. Myo and CK-MBm did not show significant changes. cTnT seems to be a potentially useful addition to the EMB results, while SAA and CRP showed variations with respect to EMB grade both in central and peripheral samples.     

C-reactive protein in the monitoring of acute rejection after heart transplantation

Histological examination of endomyocardial biopsy (EMB) is the main technique for rejection surveillance after heart transplantation. This technique is elaborate, inconvenient for the patient, and not without complications. We prospectively analyzed whether the measurement of C-reactive protein (CRP), an acute phase protein that quickly rises when there is inflammation, can serve as a marker for immunological quiescence and as an indicator for withholding EMB. During a 6-month period, CRP was measured in all patients referred for EMB as part of the routine follow-up after heart transplantation. Acute rejection in patients with a follow-up of more than 1 year was rare (1/76). In the majority of cases, EMB was taken within the 1-year post-transplantation (170/246 = 69 %). In 71/170 biopsies (42 %), CRP was ≤ 1; in the other 99/170 (58 %), CRP was ≥ 2. When CRP was ≤ 1, acute rejection was diagnosed in 12/70 cases (17 %). In contrast, acute rejection was found in 28/99 cases (28 %) with CRP ≥ 2 (P = 0.1). Although CRP is elevated more often in the presence of acute rejection, its sensitivity does not allow CRP to replace the routine performance of EMB for monitoring rejection after heart transplantation. We did, however, find a prognostic significance with regard to the effect of rejection treatment: in all acute rejections with a CRP ≤ 3 (n = 11), steroids were effective. Received: 6 January 1998 Received after revision: 7 April 1998 Accepted: 20 April 1998     

Intramyocardial impedance measurements for diagnosis of acute cardiac allograft rejection

BACKGROUND: Measurements of intramyocardial impedance at high frequencies can indicate alterations in cell membranes and intracellular spaces during acute cardiac allograft rejection. METHODS: Fifteen beagle dogs underwent heterotopic heart transplantation and were immunosuppressed with cyclosporine and methyl prednisolone (MP). Impedance was determined twice daily by means of four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intramyocardial electrogram (IMEG) were performed as reference methods. A total of 23 rejection episodes were induced. When acute rejection was recognized histologically and through IMEG readings, the animals were treated with a bolus of 125 mg of methyl prednisolone over 5 consecutive days. Treatment of rejection was controlled by biopsy and IMEG. RESULTS: All hearts showed a uniform decrease in impedance of about 28.3%+/-5.5% immediately after transplantation, which subsequently reached a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grades 1A to 1B (ISHLT) were accompanied by a statistically significant increase in impedance of 12.2%+/-2.5%; of grades 2 to 3A of 19.2%+/-3.2% and of grades 3B to 4 of 27.0%+/-2.9%. Sensitivity was 96%, specificity 91%. Successful treatment of rejection led to a decrease of impedance to the initial levels. CONCLUSIONS: The amount of increase in impedance of high frequencies is a method to stratify acute cardiac allograft rejection into grades like histologically grading. The effectiveness of rejection treatment can also be monitored through impedance measurement. The method is also applicable for telemetric rejection monitoring by means of an implantable device.     

Endomyocardial Biopsy as Risk Factor in the Development of Tricuspid Insufficiency After Heart Transplantation

Objective

Endomyocardial biopsy (EMB), which is used to monitor for rejection, may cause tricuspid regurgitation (TR) after orthotopic heart transplantation (OHT). The purpose of this investigation was to examine the occurrence of tricuspid valve tissue in myocardial specimens obtained by routine EMB performed after OHT.

Patients and Methods

From January 2000 to July 2008, 125 of the patients who underwent OHT survived more than 1 month. Their follow-up varied from 1 month to 8.5 years (mean, 5.1 ± 3.7 years). EMB was the gold standard examination and myocardial scintigraphy with gallium served as a screen to routinely monitor rejection.

Results

Each of 428 EMB including 4 to 7 fragments, totaling 1715 fragments, were reviewed for this study. The number of EMB per patient varied from 3 to 8 (mean, 4.6 ± 3.5). Histopathological analysis of these fragments showed tricuspid tissue in 4 patients (3.2%), among whom only 1 showed aggravation of TR.

Conclusions

EMB remains the standard method to diagnose rejection after OLT. It can be performed with low risk. Reducing the number of EMB using gallium myocardial scintigraphy or other alternative methods as well as adoption of special care during the biopsy can significantly minimize trauma to the tricuspid valve.     

Endomyocardial biopsies after heart transplantation. The presence of immunoglobulin/immune complex deposits

A series of 221 endomyocardial biopsies (EMB), taken from 21 patients after heart transplantation, was analyzed for the presence of immunoglobulin/immune complex deposits. Data were correlated with histology (grading following Billingham) and cytoimmunologic monitoring (CIM) on blood samples (grading into negative, rejection, or infection, based on leukocyte morphology and T cell phenotype). IgM deposits and IgG/IgM complexes in blood capillaries around myocyte fibrils were found in 78 and 40 EMB, respectively. This feature was more prevalent in EMB with a histology of rejection (39 out of 52 biopsies).