缺血性心律失常机制的电生理实验研究

本文在20只狗实验性缺血时,应用心电活动三维标测系统,对心肌“多层次双极针电极”进行电生理检查。结果表明,86%的缺血性心律失常起源于缺血区心内膜下,与缺血心肌发生延迟激动、分裂电活动及连续电活动有关,支持壁内折返机制。14%的心律失常起源于再灌注区的正常交界处的心内膜下,未记录到分裂电活动及连续电活动,支持非折返机制。     

缺血性室性心动过速折返机制的实验研究

对１８条缺血性心肌模型犬中发生室性心动过速（简称室速）的６条犬采用组合双极电极记录心肌局部电图，进一步探讨缺血性心脏病室速的机制。结果显示：①缺血区各层心肌电图和心外膜局部电图上均出现延迟电位及碎裂波。②室速的激动顺序为缺血区心内膜（作参照，为０ｍｓ）、缺血区心外膜（１０±０．１０ｍｓ）、边缘区心内膜（１０±０．１２ｍｓ）、边缘区心外膜（１６±０．２０ｍｓ）、正常区心内膜（２０±０．５０ｍｓ）、正常区心外膜为（２７±０．２０ｍｓ）。③当体表ＩＩ导联心电图和心外膜、心肌局部电图均出现心室颤动时，心内膜仍表现为室速的图形。认为室速是多平面多折返所形成的“立体折返”激动的结果；如何寻找折返环入口作为射频消融治疗的靶点至关重要     

对室性心律失常的认识及药物治疗现状

室性心律失常包括室性早搏(室早)，室性心动过速(室速)，心室扑动(室颤)及心室颤动(室颤)。持续时间少于30秒的室速称非持续性室速，超过30秒称持续性室速，有时需电击终止。按室速形态可分为单形性及多形性室速。室性心律失常常发生在有器质性心脏病的患者，但也可以发生在正常人、水一电解质和(或)酸碱平衡紊乱以及应用某些药物时。室性心律失常的发生机制有折返激动(微折返及大折返)及自律性异常     

家兔再灌注心律失常的电生理机制探讨

38只家兔,体重1.8～3.0kg。开胸结扎冠脉左室支,30分钟后剪开结扎线,实现再灌注。手术意外死亡4只。冠脉梗阻解除后出现室性早搏(24例,70.6％)和室颤(8例,23.5％),发生率P<0.05。且多于梗阻解除1分钟内出现。再灌注后电生理程序刺激共诱发出室早239次,室颤24次,非持续性室速26次,持续性室速4次。室性恢复周长随起搏周期缩短而缩短,二者呈正相关(r=0.759,P<0.05)。因此得出结论,缺血—再灌注家兔再灌注心律失常发生率很高,致命性心律失常很常见。电生理检查提示再灌注心律失常的形成很可能是触发机制。     

溶栓疗法后室性心律失常对梗塞区供血冠脉再通的预测价值

动物试验证明,冠脉再灌注常伴有室性心律失常。但临床上,心肌梗塞(MI)开始后的心律失常中有些可能是缺血心肌电不稳定的表现,而不是再灌注的结果。急性心肌梗塞(AMI)57例,于症状开始后4小时内静脉滴注链激酶。溶栓后共21例(37%)发生室性心律失常,其中加速性心室自身节律13例、非持续性室性心动过速(室速)15例,     

急性血栓性心肌缺血室性疏律失常的实验研究（1.方法学）

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,即因区心内膜下经向隔作为快径,而左室     

急性血栓性心肌缺血室性心律失常的实验研究(结果与讨论)

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.方法同左冠状动脉回旋支(leftcircumflex artery,LCX)近端释放阳极电流刺激血栓形成,结果9例发生非持续性室性心动过速(nonsustained ventricularrtachycardia,NSuVT),其激动的起源和维持在心室的不同部位.6例发生持续性室性心动过速(sustained ventriculartachcardia SuVT),其诱发是由于局灶性机制.SuVT的维持在3/6洌是由于局灶性机制,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模下经间隔作为快径,而左心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10～41 s内蜕变成心心、室颤动(室颤,ventricular fibriation,VF).1例SuVT自行终止,但于14 min后出现4个连续的室性搏动诱发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(acti-vation time,AT)在缺血前是(40±4)ms,缺血后增加达27～102 msSuVr发作前AT值(10l±28)ms比lmin前的AT值(79±15)ms明显延长(P＜0.01).VF前10个SuVT搏动的平均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是由于心叽内多发折返.AT是一个敏感参数,它与恶性室性心律失常发作呈正相关,而且在稳定性室性心动过速组与室性心动过速演变为心室颤动组之间有明显差别.     

急性ST段抬高心肌梗死患者再灌注心电图变化及其可能的影响因素

目的 探讨急性ST段抬高心肌梗死(STEMI)患者缺血再灌注损伤心电图改变及其发生机理.方法 分析60例STEMI患者再灌注治疗(溶栓或冠状动脉介入治疗)后缺血再灌注损伤性心电图改变特点及影响因素;根据再灌注治疗后是否发生再灌注损伤性心电图改变而将患者分为再灌注损伤性心电图改变组和再灌注无损伤性心电图改变组;抽静脉血测定活性氧(ROS)、丙二醛(MDA)、还原型谷胱甘肽(GSH)、总抗氧化力(T-AOC)及γ-谷氨酰半胱氨酸合成酶(γ-GCS)活性.结果 再灌注心电图心律失常发生率高(65.00%),且以加速性室性自主心律最多见,其次非持续性室速、窦缓和房室传导阻滞;并易出现再灌注损伤性ST段抬高(46.67%).单因素分析发现冠状动脉血管病变数目、发病至CK达高峰时间、再灌注时间与STEMI患者易发再灌注损伤性心电图改变有关(P<0.05).溶栓治疗再灌注损伤性心电图改变发生率高于冠状动脉介入治疗(P<0.05).再灌注心电图改变组血清ROS、MDA显著增高而GSH、T-AOC显著降低;γ-GCS活性高于对照组和缺血组(P<0.05).结论 STE-MI患者缺血再灌注后再灌注损伤性心律失常与ST段抬高较常见;再灌注复氧后产生氧自由基增多,自由基生成系统/清除系统失衡,可能是发生再灌注损伤性心电图改变重要机制.     

非接触球囊标测指导血流动力学不稳定性或非持续性室性心动过速的射频消融

目的探讨非接触球囊标测在指导血流动力学不稳定性或非持续性室性心动过速(室速)射频消融中的作用。方法17例室速患者,年龄50岁±9岁,经心室刺激诱发血流动力学不稳定性或非持续性室速后,使用非接触标测系统ENSITE3000标测室速的出口和(或)慢传导区,然后使用温控大头导管在室速出口作环形消融或横跨慢传导区进行线性消融。结果17例患者共诱发18次室速,周长为336MS±58MS。15例患者可确定室速的出口,为QRS波前10MS±16MS;其中5例是心肌梗死后室速,9例为右室流出道室速。5例心肌梗死后室速均可确定舒张期慢传导区,最早的心内膜舒张期电活动在QRS波前60·1MS±42·6MS。3例非持续性室速均可确定最早的心室激动点。18次室速中15次消融成功,1例没有进行消融,2例消融失败。结论非接触球囊心内膜标测能成功指导血流动力学不稳定性或非持续性室速的射频消融。     

束支折返性心动过速

束支折返性心动过速(bundle branch reentrant tachycar-dia,BBR-T)是折返性室性心动过速(室速)的一个类型,约占所有诱发室速的6%[1].BBR-T是人类心室折返激动中惟一具有清晰明确的折返环的室速.希氏束(至少其远段)-束支-浦肯野系统(HPS)和心室肌是折返环的必需组成部分[2].BBR-T也呈持续性单形室速,远比伴随冠心病、心肌梗死后的室速少见.     

Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium

The mechanisms responsible for malignant ventricular arrhythmias associated with reperfusion of ischemic myocardium were delineated with a computerized, three-dimensional mapping system, with simultaneous eight-level transmural recordings from 232 bipolar sites. In six chloralose-anesthetized cats, regional ischemia was induced for 10 min by occlusion of the left anterior descending coronary artery, followed by reperfusion. At 10 min after ischemia, just before reperfusion, total ventricular activation time during sinus rhythm was significantly delayed (63 +/- 8 vs 25 +/- 2 msec before ischemia, p less than .001). Ventricular tachycardia (VT) occurred within 15 sec after reperfusion and in three animals culminated in ventricular fibrillation. In 75% of cases of nonsustained VT, initiation occurred in the subendocardium, at the border of the reperfused zone via a mechanism not involving reentry, as determined by the fact that continuous activation was not apparent and the time from the end of the sinus beat to the beginning of VT (142 +/- 14 msec) was not associated with any intervening depolarizations. In the remaining 25% of cases of nonsustained VT, initiation of the VT resulted from intramural reentry in the subendocardium adjacent to the site of delayed midmyocardial activation from the preceding sinus beat (total activation time = 151 +/- 9 msec, p less than .001 vs just before reperfusion). This reentrant mechanism was similar to that responsible for the majority of cases of VT during ischemia without reperfusion. Maintenance of VT during reperfusion occurred by nonreentrant mechanisms as well as by intramural reentry, with most cases of VT involving both mechanisms. Ventricular tachycardia leading to ventricular fibrillation was initiated in the subendocardium at the border of the reperfused zone by a nonreentrant mechanism and was maintained by both nonreentrant and reentrant mechanisms, at times in combination in the same beat. The coupling interval of the first ectopic beat of VT leading to ventricular fibrillation was not significantly different from that of nonsustained VT (199 +/- 16 vs 189 +/- 9 msec, p = NS). However, during the transition from VT to ventricular fibrillation, nonreentrant mechanisms arising both in the subendocardium and subepicardium led to very rapid acceleration of the tachycardia to the coupling interval of 92 +/- 2 msec, resulting in enhanced functional block and further conduction delay, with the total activation time of the transition beats exceeding the coupling interval of the tachycardia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reduction of reperfusion injury in the canine preparation by intracoronary adenosine: importance of the endothelium and the no-reflow phenomenon

We hypothesized that the endogenous coronary vasodilator adenosine may reduce infarct size by progressively increasing reflow in a preparation of coronary occlusion-reperfusion. After 90 min of proximal left anterior descending artery occlusion, 20 dogs were randomized to blood reperfusion with (n = 10) or without (n = 10) adenosine into the proximal left anterior descending vessel at 3.75 mg/min for 60 min after reperfusion. Regional myocardial blood flow was determined serially with microspheres and regional ventricular function was assessed by a computerized radial shortening method. At 24 hr, the area at risk was defined in vivo with monastral blue dye and area of necrosis was determined after incubation of left ventricular slices in triphenyltetrazolium chloride. Hemodynamic variables were similar in the two groups during the experimental protocol. Infarct size was significantly reduced in treated animals, both when expressed as a percentage of the area at risk (9.9 +/- 2.8% vs 40.9 +/- 6.6%, p less than .001) and as a percentage of the left ventricle (4.6 +/- 1.3% vs 18.0 +/- 3.4%, p = .002). This was associated with significant improvement in radial shortening in the ischemic zone 24 hr after reperfusion (10.1 +/- 2.5 vs -2.8 +/- 2.2%, p less than .01). Regional myocardial blood flow was significantly increased in endocardial and epicardial regions from the lateral ischemic zone 1 hr after reperfusion in adenosine-treated animals. Light microscopy demonstrated decreased neutrophil infiltration in the ischemic zone and electron microscopy showed relative preservation of endothelial structure in the subendocardium with reduced neutrophil and red cell stagnation of capillaries in the treated group. These findings suggest that intracoronary administration of adenosine after reperfusion significantly reduces infarct size and improves regional ventricular function in the ischemic zone in the canine preparation.     

非持续性室性心动过速诊疗进展

非持续性室性心动过速（nonsustained ventricular tachycardia,NSVT）在健康个体和心脏病患者均可发生.无心脏病NSVT患者的预后尚不明确.在运动时,尤其是运动后恢复,检测到NSVT,预示几十年内心血管死亡率增加.经常训练的运动员,若停止训练,NSVT的预后一般良好.非ST段抬高急性冠脉综合征患者住院48 h后发作的NSVT,特别是缺血发作时出现,心脏性猝死风险增加.急性心肌梗死患者住院13～24 h后发生NSVT提示预后不良.接受再灌注治疗并服用β阻滞剂的心肌梗死患者,以左心室射血分数等因素进行多变量分析发现NSVT不是预测远期死亡率的独立因子.NSVT对肥厚型心肌病及大多数离子通道病患者具有预后判断价值,但对缺血性心力衰竭和扩张型心肌病的预后价值不明.治疗NSVT的重点是治疗基础心脏病.     

Mechanisms underlying the development of ventricular fibrillation during early myocardial ischemia

The mechanisms underlying the development of ventricular fibrillation (VF) during early myocardial ischemia were assessed by use of a computerized three-dimensional mapping system capable of recording simultaneously from 232 intramural recording sites throughout the entire feline heart in vivo. Occlusion of the proximal left anterior descending coronary artery led to ventricular tachycardia (VT), which degenerated to VF in 1-5 minutes in four of 15 animals. Normal sinus beats immediately preceding the initiation of VT leading to VF demonstrated delayed activation (total activation time 133 +/- 14 msec), which was not significantly different from the activation time for normal sinus beats immediately preceding nonsustained VT (149 +/- 7 msec). Most of the conduction delay occurred in the subendocardial and midmyocardial regions in both groups. Initiation of VT leading to VF occurred by intramural reentry in three of the four cases. In one case, a mechanism responsible for the initiation of VT could not be assigned. The coupling interval of the initiating beats of VT ultimately leading to VF (210 +/- 15 msec) did not differ from that of nonsustained VT. Maintenance of the VT that led to VF was due primarily to intramural reentry (84% of cases) involving multiple activation sites in and around the border region of the ischemic zone. Nonreentrant mechanisms, arising in the subendocardium and subepicardium, also contributed to the maintenance of VT before development of VT. The transition from VT to VF was due exclusively to intramural reentry with initiation of the reentrant beats in the subendocardium and, occasionally, the subepicardium. Acceleration of the tachycardia by intramural reentry, along with very rapid and inhomogeneous recovery of excitability (as low as 50-60 msec), led to increased functional block and conduction delay. As a result, the total activation time for a given beat exceeded the coupling interval for that beat and led to the multiple reentrant circuits and multiple simultaneous activations characteristic of VF. Thus, the initiation and maintenance of VT leading to VF during early ischemia is due to intramural reentry, although nonreentrant mechanisms also contribute. However, the development of VF is due to continued intramural reentry and rapid recovery of excitability.     

Neutrophil depletion fails to modify myocardial no reflow and functional recovery after coronary reperfusion

Recent studies suggest that neutrophil accumulation and activation in postischemic myocardium may be responsible for myocardial no reflow, which is characterized by an incomplete restoration of blood flow after reperfusion. To examine this further, 11 open chest, anesthetized dogs received bolus injections of a bovine neutrophil antiserum that produced an average 81 +/- 5% depletion of circulating neutrophils, and 10 control dogs received nonimmune serum. Each animal underwent 2 h of left circumflex artery occlusion followed by 4 h of reperfusion. Simultaneous two-dimensional echocardiography and radioactive microsphere blood flow studies were performed at baseline, 2 h of occlusion and early (approximately 5 min) and 4 h of reperfusion. During occlusion, both groups developed similar reductions in myocardial blood flow and levels of ischemic zone myocardial wall thinning. At early reperfusion, similar levels of hyperemia and regional hypokinesia were observed for both groups. By late reperfusion, both groups experienced significant no reflow in the subendocardium (p less than 0.05) and reduced reflow in the mid-myocardium. Regional depression in ischemic zone function persisted throughout the reperfusion period in both groups. However, infarct size expressed as a percent of left ventricular weight, assessed by triphenyltetrazolium chloride staining, was smaller for the neutrophil depletion group compared with the control group (8.7 +/- 1.3% versus 13.1 +/- 1.8%, p less than 0.05). It is concluded that an 81% neutrophil depletion fails to modify the no reflow phenomenon or improve functional recovery after 2 h of coronary artery occlusion and 4 h of coronary reperfusion despite modification of the ultimate size of necrosis.     

Regional myocardial blood flow and ventricular arrhythmias following one-stage and two-stage coronary artery occlusion in anesthetized dogs

Experiments were performed in 29 anesthetized dogs to compare effects of one-stage and two-stage coronary artery occlusion on ventricular arrhythmias and regional myocardial blood flow (MBF). Two periods of arrhythmias were observed and both were associated with evidence suggesting reentry; i.e., activity in ischemic zone electrograms which bridged the diastolic intervals preceding ventricular ectopic beats. Early ventricular arrhythmias followed progressive deterioration of conduction in the ischemic zone, whereas later arrhythmias occurred unexpectedly with the sudden appearance of bridging activity. One-stage occlusion produced a higher incidence of ventricular arrhythmias and ventricular fibrillation than two-stage occlusion. However, there was no difference in central ischemic zone blood flow, indicating that the protective effect of two-stage occlusion was not due to greater blood flow in this region. These results suggest that factors other than the degree of MBF reduction are important determinants of the incidence and severity of ventricular arrhythmias following coronary artery occlusion.     

Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model.

The time course of ventricular arrhythmias in the early period (0--30 minutes) after ligation of the left anterior descending coronary artery was studied in 41 open-chest mongrel dogs anesthetized with pentobarbital sodium (Nembutal). ECGs and seven single and composite electrograms from various regions in and around the ischemic zone were recorded throughout the experiments. Two periods of ventricular arrhythmias were clearly seen. The first occurred 2--10 minutes after coronary ligation, peaking at 5--6 minutes, and was designated as immediate ventricular arrhythmias (IVAs). There was a distinct correlation between incidence, severity, onset and termination of IVA and the degree of local delay and fragmentation of the normal sinus activation spread in the ischemic subepicardial zone. The second wave of ventricular arrhythmias occurred 12--30 minutes after ligation independently of the previous increased delay and fragmentation of activation in the ischemic subepicardium. Delayed ventricular arrhythmias (DVAs) were as severe as IVAs--there were nine instances of ventricular fibrillation during DVA and seven during IVA. While the mechanism of IVA is most probably related to reentry accompanied by delay and fragmentation of ischemic subepicardial activation, the mechanism of DVA remains unclear. Our evidence suggests that DVAs are also reentrant, with the reentry pathways located in deep myocardial structures or involving microscopic pathways at the Purkinje muscle junction.     

Amlodipine, a long-acting calcium antagonist drug reduces ischemia-induced ventricular conduction delay in pig hearts

The effects of amlodipine, a novel, long-lasting calcium channel blocking agent, on ischemia-induced myocardial conduction delay was studied in anesthetized pigs paced at a constant heart rate. Acute coronary occlusion (3 minutes) significantly lengthened time to onset, time to peak and duration of bipolar electrograms recorded from both subendocardial and subepicardial left ventricular sites. After intravenous injection of amlodipine (0.3 mg/kg, n = 6), subsequent periods of ischemia greatly reduced (p less than 0.01) all indexes of subepicardial conduction delay. In the subendocardium, amlodipine decreased only time to onset (-25 +/- 4%, p less than 0.01) within the ischemic zone. Significant delays in all indexes were present during repeated ischemic periods in the placebo-treated control group (n = 5). Amlodipine also increased regional myocardial blood flow within the nonischemic myocardium by 25 +/- 10% and decreased mean aortic pressure by 7 +/- 2% without altering flow in the ischemic region. Left atrial pressure remained unchanged. Indexes of ischemia-induced conduction delay were more rapidly restored after reperfusion in amlodipine-pretreated than in control animals. In conclusion, amlodipine produced a beneficial blood flow-independent effect on ischemia-induced injury potentials. The effect may help to reduce the likelihood of development of lethal ventricular arrhythmias in the early stage of myocardial ischemia in the clinical setting.     

Normothermic ischemic cardiac arrest of the isolated working rat heart. Effects of time and reperfusion on myocardial ultrastructure, mitochondrial oxidative function, and mechanical recovery

The ischemic state of the myocardium of the isolated working rat heart after induction of normothermic ischemic cardiac arrest was assessed by the interrelationship among changes in myocardial ultrastructure, mitochondrial oxidative phosphorylation, and tissue high energy phosphate contents. At all time intervals (10-40 minutes) studied, the ultrastructural changes were more severe in the subendocardium than in the subepicardium. After 25-40 minutes of normothermic ischemic cardiac arrest, the mitochondrial oxygen uptake (state 3) became increasingly depressed, particularly in mitochondria isolated from the subendocardium. Mitochondrial oxidative function, as measured in vitro, did not correlate well with mitochondrial ultrastructural damage. In addition, the effects of coronary reperfusion on the ability of the ischemic heart to recover in terms of ultrastructure, mechanical, and metabolic function were evaluated. Hearts subjected to 10-40 minutes of normothermic ischemic cardiac arrest showed almost complete ultrastructural recovery of the subepicardium upon reperfusion; regression of ultrastructural changes occurred to a lesser extent in the subendocardium. Reperfusion for 30 minutes did not alleviate the depression in mitochondrial oxidative function, while tissue ATP levels did not return to control, preischemic levels. After 20 minutes of normothermic ischemic cardiac arrest, the mechanical performance of the working heart during reperfusion was significantly depressed, compared with pre-ischemic control values. Normal ultrastructure of the subendocardium always accompanied mechanical recovery, while improvement of mitochondrial oxidative function was not essential.