关键词： 血栓形成；心肌缺血；室性心律失常

【摘要】目的用三维标测方法观察急性冠状动脉血栓性心肌缺血室性心律失常的机制。方法向左冠状动脉回旋支(LCX)近端释放阳极电流刺激血栓形成。结果9例发生非持续性室速(NSuVT)，其激动的起源和维持在心室的不同部位。6例发生持续性室速(SuVT)，其诱发是由于局灶性机制。SuVT的维持在3/6例是由于局灶性机制，另3例SuVT的维持，是由于心肌内的一个大折返径路，即以前壁缺血区心内膜下经间隔作为快径，而左室后壁心外膜并经心肌内返回心内膜下作为慢径。4/6例SuVT在10～41s内蜕变成心室颤动(室颤，VF)。1例SuVT自行终止，但于14 min后出现4个连续的室性激动诱发VF。VF诱发是由于多发的折返波形成。平均总的心肌激动时间(AT)在缺血前是(40±4)ms，缺血后增加达27～102 ms。SuVT发作前AT值(101±28)ms比1 min前的AT值(79±15)ms明显延长(P＜0.01)。VF前10个持续性室速激动的平均AT值为(169±29)ms，比SuVT没有发展为VF的犬的AT值明显延长。结论LCX的血栓栓塞可导致90%的犬出现NSuVT，60%的SuVT及50%的VF。局灶性机制是大多数NSuVT机制，也是SuVT诱发机制。SuVT的维持可由于局灶性机制，也可由于缺血区域从心外膜经心肌内传导到心内膜下的折返机制。VF是由于心肌内多发折返。AT是一个敏感参数，它与恶性室性心律失常发作呈正相关，而且在稳定性室速组与室速演变为室颤组之间有明显差别。

Animal study of ventricular arrhythmias induced by acute thrombotic coronary occlusion (I.Methodology)

ZHANG Shu.Fuwai Hospital,Chinese Academy of Medical Sciences,Beijing 100037

【Abstract】ObjectiveSpontaneous sustained ventricular tachycardia(SuVT) and its progression to ventricular fibrillation (VF) induced by coronary artery thrombotic occlusion were characterized using three-dimensional mapping in ten open-chest dogs.MethodsRegional ischemia was induced by thrombotic occlusion using a wire electrode to deliver a 200～300 μA anodic current to the intima of the proximal left circumflex artery (LCX).ResultsTotal occlusion occurred 47 minutes after onset of the current as indicated by a Doppler flowmeter.In nine dogs,nonsustained VT (NSuVT) was initiated and maintained from numerous,different focal sites of origin.VT occurred in six dogs (group A) and was also initiated by focal mechanisms located near the ischemic border in four dogs and within the ischemic region in the other two.In three dogs,the SuVT was maintained primarily through a focal mechanism,which arose in the ischemic border region.In the other three dogs,VT was maintained by macroreentry that extended from the subendocardium of the ischemic region anteriorly through the septum as the fast pathway,towards the epicardium of the posterior area of LV and then intramurally back to the subendocardium as the slow pathway.VT degenerated into VF in 10～41 seconds in four of these six dogs.In one case,VT stopped spontaneously but was followed 14 min later by 4 cycles of VT that initiated VF.The transition from VT to VF was due exclusively to intramural reentry with multiple wavefronts involving the nonischemic region in three dogs,the ischemic border region in one,and the ischemic region in one.The mean total activation time (AT) in the control state was 40±4 ms,AT started to increase near the time of total LCX occlusion.The maximal increase was 27～102 ms.The AT of the ten sinus cycles before VT (101±28ms) was significantly longer than 1 minute before VT (79±15 ms p＜0.01).In four dogs,VT occurred 3～7 minutes after total occlusion when the AT increased to 98～146 ms.The AT in the four dogs without VT (group B) was always less than 98 ms.The mean AT of the first ten cycles of VT in those dogs in which VT degenerated into VF (169±29 ms) was significantly longer than that in the two dogs in which VT remained stable without degenerating into VF.ConclusionThrombotic occlusion of the LCX induced NSuVT in 90%,VT in 60%,and VF in 50% of the dogs.Focal mechanisms underlay most NSuVT and the initiation of VT.VT was maintained either by a focal origin near the ischemic border or by reentry,which propagated intramurally from the epicardium to the subendocardium in the ischemic region.VF was maintained exclusively by intramural reentry involving the ischemic region,border,and nonischemic regions.AT is positively correlated with malignant ventricular arrhythmias and may differentiate VT that remains stable from that which progresses to VF.

【Key words】ThrombosisCardiacischemiaVentriculararrhythmia

心脏性猝死是全球主要死亡原因^［1，2］，常常是因为急性冠状动脉缺血导致的室性心动过速(VT)和随之发生的心室颤动(VF)。许多作者已经描述了其心律失常的发作可由于折返和局灶自律性两种机制^［3～5］，但是对于急性冠状动脉缺血时VT/VF发生的精确的电生理机制尚未完全明了。

冠状动脉缺血所致自发性VT的发生率因实验模型差别和多种影响因素存在而不同^［6］。而以往缺血性心律失常的研究大多使用非血栓性冠状动脉阻塞的模型，而事实上血栓形成是临床上急性冠状动脉阻塞的主要原因^［7～11］，因而其实验结果不能准确反映血栓性冠状动脉缺血所致VT的临床特征。VT的发生率在血栓性阻塞的模型中较非血栓性阻塞的高^［12］，可能是由于心肌细胞对血栓过程中释放的致心律失常因子的作用^［13］。阻塞动脉的不同也会影响心律失常的发生率。有报道犬的左回旋支(LCX)阻塞比左前降支(LAD)阻塞更易发生心律失常^{［2，6，14，15］}，然而也有不同结果的报道^［16］。

以往心电活动的标测大多是从心外膜记录的，而心内膜和内膜下组织在心律失常的发作过程中也起着重要的作用。Pogwizd等^［17］用三维标测同步记录了猫心脏的232个心肌内位点心电图，结果显示折返涉及心肌内组织，因此心外膜标测并不能充分认识急性缺血时心肌电生理的变化和心律失常的机制。同时在心肌缺血时，心脏的传导缓慢而不均匀^［18］，因此标测用电极密度高低对测定传导特性和激动方式非常重要，但以前研究用的电极密度的排列却是有限的^{［3，6，19～21］}。

本组报道我们应用针形高密度电极三维标测技术进行开胸犬实验，观察急性血栓阻塞性冠状动脉缺血情况下自发性室性心律失常的电生理机制。

资料和方法

1.血栓性冠状动脉缺血动物模型制备

10只杂种犬，体重12～17 kg，实验前禁食12 h。每只动物均使用戊巴比妥钠(30 mg/kg)静脉注射诱导麻醉并以异氟烷(1%～3%)维持。动物气管插管予以呼吸机正压通气，潮气量10～15ml/kg。左右股动脉插入两根7 F导管以测定动脉血压、血气和电解质。监护肢体导联和V₁导联心电图，维持体温在37℃。

正中切口开胸后，暴露心脏并将其悬吊在心包床内。游离LCX的近端约15～20 mm，并在其最近端置入一个多谱勒探头(Iowa)监测动脉血流，远端插入一根铜丝导线，将非绝缘的针尖固定在血管内膜表面用以释放致栓电流^［22］。游离LCX动脉最远端缝扎形成一个约50%的机械性狭窄。导线连接一个带可调阻抗的9 V电源，电源回路接到胸壁，以此向LCX内表面释放200～300 μA电流。电流从200 μA起，每30 min增加50 μA，直到多谱勒证实LCX血流全部阻断(图1)。

图1血栓阻塞性冠状动脉缺血动物模型(说明见正文)

实验终点是自发性VF。如果LCX被全部阻断1 h后未发生VF，静脉注射10 ml氯化钾(KCl)处死动物。实验结束后，切除心脏但保持针式标测电极的位置不变，用生理盐水冲洗心脏，主动脉压力灌注(100 cmH₂O)2L福尔马林。福尔马林固定24 h后以彩色塑管取代针式电极后，记录电极位置图。

2.插入针式电极的构造与定位和心电标测系统

针式电极是由直径50 μm的聚四乙氟绝缘银电线穿入21号不锈钢针内构成。左室针式电极有四极，极间距3.5 mm。右室针式电极有三极，极间距2.5 mm。室间隔的针式电极为六极，极间距3.5 mm。针式电极在离最近端电极1.5 mm处弯成90°角，以便最近端的电极位于心外膜下1 mm。左室插入63根针电极，右室插入28个根针电极。前后间隔置入14个根针电极。在左室面的针式电极的密度平均间距是5～10 mm，右室表面为10～15 mm，间隔上为6～12 mm(图2)