摘要
研究背景：
缺血性心脏病是引起持续性单形性室性心动过速(VT)的最常见原因，常导致血流动力学紊乱，并可诱发心室颤动和猝死。现有的治疗方法中，抗心律失常药物治疗这类VT的效果较差，长期应用可出现严重的副作用；植入性心脏转复除颤器(ICD)虽可有效预防室速和心室颤动引起的猝死，但它不能预防和减少室速的发作，而且价格昂贵；外科手术治疗风险大且复发率较高。随着导管消融技术在治疗室上性心律失常和非器质性心脏病室速中的成功，器质性心脏病VT尤其是缺血性心脏病VT导管消融已成为研究的重点，希望通过运用这一微创、安全的治疗方法能消除或减少VT的发作，但目前采用常规标测方法指导电生理机制复杂的器质性心脏病VT导管消融，手术成功率仍较低。最近出现的新型标测系统和方法可望提高VT的消融成功率。
缺血性心脏病VT发病机理尚不十分明确，其电生理机制也十分复杂。目前对心肌梗死后期心肌细胞心电重构现象、病理生理机制及其在发生室性心律失常、心功能改变中的作用等方面认识尚不充分，对它们作进一步的探讨已成为心肌梗死后室性心律失常研究中的热点。心肌细胞离子通道在维持心脏正常有效功能方面起重要作用，几乎所有心脏疾病均与离子通道异常有关。部分研究已经证实心肌梗死后VT动物模型的心肌细胞重构过程中膜离子通道特性及其基因表达、蛋白水平等均有所改变。至于有何改变，这些改变在心律失常发生中所起的确切作用等目前尚有争议，需待进一步研究和探讨。
目的
(1)运用PTCA球囊堵闭猪冠状动脉，造成急性心肌梗死(AMI)，AMI后数周通过电生理方法建立持续性单形性VT的非
南京医科大学博士学位论文
开胸法动物模型，并探讨 VT的诱发方式、成功率和时间窗等。
C 采用单相动作电位记录方法观察。肌梗死后VT的左。
室。。肌细胞单相动作电位及有效不应期的改变，研究。C肌梗死后重
构心肌细胞电重构现象及电生理基础。
。O）运用分子生物学方法 RTPCR技术，半定量研究心肌细
胞膜多种钾离子通道基因和间隙连接蛋白Connexin43基因flin－tyA
表达的变化，探讨。。肌梗死引发心电重构继而导致VT发生的分子
”机制。
K 在建立猪。Gi几梗死后单形性持续性VT的基础上，运用
非接触心 内膜球囊标测系统（Ensite 3000系统）进行VT的心内膜
标测，研究 Ensite 3000 系统在心内膜电位、。CjLA痕组织标测的
方法，探讨心肌梗死后 VT的电生理机制，运用该系统指导心肌梗
死后持续性单形性 VT的标测和消融方法，并通过与病理比较，观
察系统疯痕标测和指导线性消融的准确性。以期通过新型标测系统
的运用提高缺血性心脏病VT导管消融成功率。
m 采用非接触球囊导管标测系统（Ensite 3000系统）指导
难治性VT包括器质性。G脏病VT的标测与射频消融，探讨非接触
。G内膜球囊标测系统在VT标测和消融中运用方法及其价值。
方 法
门） 猪19只，平均体重30 t skg。分为两组，一组13 R，
为MI组，接受冠脉造影、左室造影和PTCA球囊堵闭LAD，形成
AMI数周后诱发VT，另一组 6 R，作为对照组，只接受冠脉造影
＿和左室造影，不作PTCA球囊堵闭，饲养大致相等的时间后与MI
组进行相同的研究。
m 两组动物在麻醉后经颈总动脉或股动脉置入动脉鞘，进
。行冠脉造影和左室造影，MI组置入PTCA球囊堵闭左前降支
（LAD），造成猪急性前壁。G肌梗死。存活的9只猪在AM数周后
经左室造影、超声。。动图检查证实在左室。。尖、前壁和前间隔室壁
瘤形成；同时观察猪结构和功能在。G肌梗死前后的变化。术后2上
周内对9只存活猪进行卜 次电生理检查，子以心室程序电刺激方
式诱发持续性单形性VT，观察VT诱发、终止的方式及VT诱发
－5－
南京医科大学博士学位论文
的时间窗等。
刀 运用单相动作电位记录方法；记录猪左，C室不同部位的
MAP；观察 MAP各电生理参数及 Eny在 VT形成前后的变化。这
些参数包括从激动开始至复极50％的时间APD扣，复极90％的时间
小APD。。；激动时间（AT）、复极时间（RT）和AT、APD；。、APD。。、
RT的离散度，即 ATd、APDdl、APDd。、RTd以及ERPd，探讨 VT
产生的细胞电生理机制。
一 W 对。。肌梗死后持续性单形性VT猪模型 4只，经股动脉
和股静脉穿刺后，2只猪在左。。室内，另2只猪在左、右心室内各
置N一 Ensite 3000球囊，分别构建左、右。U室的＝维几何模型；
运用电压标测?
Backgrounds
Ischemia heart disease is the most common cause of sustained monomorpic ventricular tachycardia (VT). Among of the management of this arrhythmia , antiarrhythmia drugs have poor efficacy at suppressing VT and have been associated with long-term side effects including proarrhythmia and excess mortality. Although ICD have been shown to significantly reduce arrhythmic deaths, these devices do not affect the occurrence or frequency of VT. Furthmore, due to their high cost, an ICD is not an option for many patients. The major drawback to arrhythmia surgery is the operative morbidity and mortality. With the success of radiofrequency catheter ablation (RFCA) in supreventricular tachycardia and idiopathic ventricular tachycardia, ablation of VT with organic heart disease especially ischemia heart disease is becoming the major area of study. RFCA offers hope of preventing VT recurrence, avoiding antiarrhythmic drug toxicities, and the risks of surgery. However, RF ablation of VT due to ischemia heart disease continues to be one of the most challenging procedures in clinical elsctrophysiology. Because of the limitation of conventional mapping methods, the successful rate of ablation of the VT is lower. A number of technological innovations including non-contact mapping system may improve the ease and efficacy of catheter ablation.
The mechanism of VT due to ischemia heart disease is not clear and the electrophysiological mechanism is very complex. Further
investigation about cardiac remodeling, mechanism of pothophysiology and the actions of these changes in resulting in ventricular arrhythmia and cardiac function after myocardial infarction are needed. Ionic channels of myocardium play a key role in maintaining normal heart function. Nearly all heart disease is related to the abnomality of ionic channels. Partial studies have certified that characteristic of ionic channels and expression of these ionic channel genes had some changes in the course of cardial remodeling after experimental MI. There are many controvert about ionic channel how to change and what exact actions in causing ventricular arrhythmia. Studies about them need to go step further. Objective
(1) To develop a close-chest pig model of sustained monomorphic ventricular tachycardia after myocardia infarction and to investigate induce method and successful rate of inducing VT in experimental MI model.
(2) Using monophasic action potential (MAP) recording technique, we observe the changes of MAP and effective refrectory period (ERP) in the porcine model of healed myocardial infarction and investigate the electric remodeling and electrophysiologic mechanism of sustained monomorphic ventricular tachycardia
(3) Using the technique of semiquantitative reverse transcriptase- polymerase chain reaction (RT-PCR), we research the alterations of the expression of three potassium channel subunits and connexin43 gene after experimental myocardial infarction and discuss the cellular and molecular bases of arrhythmias in the postinfarction remodeled ventricular myocardium. The molecular mechanism of post-Mi ventricular arrhythmias is discussed with the research.
(4) On the basis of establishing the model of sustained monomorphic ventricualr tachycardia of healed myocardial infarction, we investigate the accuracy of scar mapping and navigation of the
noncontact mapping system through correlation with pathology analysis. We also explore the electrophysiologic mechanisms and methods of mapping and catheter ablation of ventricular tachycardia in the porcine model of healed infarction using noncontact mapping system (EnSite 3000 system).
(5) To assess the clinical utility and value of EnSite 3000 system for mapping and radiofrequency catheter ablation of refractory ventricular tachycardias include organic heart disease.
Methods
(1) Nineteen pigs that weighed 30 ?5kg were studied. Thirteen pigs underwent coronary artery angiogr
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