心室肌复极快慢与尖端扭转型室性心动过速发生率的性别差异

目的 :观察雌雄兔离体心室肌复极时程的差异 ,探讨其与尖端扭转型室性心动过速 (TdP)性别差异的关系。方法 :以Langendorff法依次用台氏液、含索他洛尔的台氏液和含索他洛尔的低钾、镁台氏液灌流离体兔(雌雄各 8只 )心 ,记录雌、雄兔心用索他洛尔前后心内膜单相动作电位 ,比较雌雄兔在低钾、镁台氏液灌流后TdP发生率的差异。结果 :用索他洛尔前 ,起搏周期 (CL)从 4 0 0ms延长至 180 0ms,雄兔内膜单相动作电位时程复极90 %的时限 (MAPD90 )由 (181.0± 6 .5 )ms延长到 (2 14 .0± 7.5 )ms ,增幅 (18.2± 8.3) % ;雌兔内膜MAPD90 由(186 .0± 6 .3)ms延长至 (2 76 .0± 8.2 )ms。增幅 (48.4± 9.4 ) %。用索他洛尔后 ,CL从 4 0 0ms增至 180 0ms,雄兔内膜MAPD90 由 (2 2 4 .0± 6 .9)ms延长到 (2 95 .0± 7.6 )ms ,增幅 (31.7± 8.7) % ;雌兔内膜MAPD90 由 (2 34.0±6 .3)ms延长至 (376 .0± 9.7)ms,增幅 (6 0 .7± 8.5 ) %。用索他洛尔前后雌兔内膜MAPD90 均明显长于雄兔 (P<0 .0 1)。 7只雌兔发生TdP ,发生率 87.5 % ;1只雄兔发生TdP ,发生率 12 .5 %。结论 :复极快慢的不同可能是TdP发生率性别差异的主要原因     

心房不同部位起搏对家兔房室结电生理特性的影响

探讨心房不同部位起搏对离体家兔房室结电生理特性的影响。方法采用等量血液－台氏液，以Ｌａｎｇｅｎｄｏｒｆ装置持续灌流离体兔心，分别从房间隔和终末嵴刺激心脏，观察从上述两个部位起搏心脏时，ＡＶＮ前传的各面电生理参数。结论心房不同部位起搏心脏对该模型兔心ＡＶＮ电生理特性无影响。     

抗心律失常肽对低钾低镁条件下伊布利特致尖端扭转性室性心动过速的影响

目的探讨缝隙连接开放剂抗心律失常肽(AAP10)对低钾、低镁条件下伊布利特致尖端扭转性室性心动过速(TdP)及心肌电不稳定性的影响。方法 54只日本长耳大白兔随机制备成左室楔形心肌块模型,随机分为对照组、低钾低镁组、伊布利特组、低钾低镁伊布利特组和AAP10干预组。对照组灌流正常台氏液,低钾低镁组灌流低钾低镁台氏液,伊布利特组灌流浓度2mg/l的伊布利特,低钾低镁伊布利特组灌流溶有同浓度伊布利特的低钾低镁台氏液,AAP10组给予AAP10干预的条件后灌流溶有伊布利特的低钾低镁台氏液。比较各组早期后除极(EAD)、R on T室性早搏和TdP的发生情况,以及QT间期、T波顶点到终点距离(Tp-e)和Tp-e/QT的变化。结果与对照组比较,低钾低镁伊布利特组QT间期、Tp-e和Tp-e/QT延长,EAD、R on T室性早搏、TdP的发生率明显增多。AAP10干预组,TdP、QT间期、Tp-e和Tp-e/QT比低钾、低镁伊布利特组显著减少。结论 AAP10可能通过开放缝隙连接减少跨壁复极离散度,从而起到预防伊布利特在低钾、低镁条件下的致TdP的作用。     

伊布利特致尖端扭转性室性心动过速机制的研究

目的:探讨特效转复心房颤动药物伊布利特致尖端扭转性室性心动过速(Tdp)的机制。方法:利用兔左室楔形心肌块灌流伊布利特或溶有伊布利特的低钾低镁台氏液。30只新西兰大白兔随机分为正常组、伊布利特组和低钾低镁组,每组10只。正常组灌流台氏液,伊布利特组灌流2 mg/L伊布利特40 min,低钾低镁组灌流同浓度但溶于低钾低镁台氏液的伊布利特。同步记录各组内、外膜下心肌动作电位和容积心电图,观察灌流过程中早后除极(EAD)和Tdp的发生情况,对QT间期以及跨室壁复极离散度(TDR)的影响。结果:伊布利特组QT间期较正常组显著延长[(337±46)ms∶(548±73)ms],TDR也显著增加[(49±15)ms∶(132±36)ms],EAD的发生率为4/10,与正常组比较,均P<0.05;Tdp的发生率为0。低钾低镁组QT间期近一步延长至(652±184)ms、TDR增至(157±59)ms,EAD发生率为5/10,与正常组比较,均P<0.05,与伊布利特组比较,均P>0.05;Tdp的发生率增加为7/10,与正常组、伊布利特组比较,均P<0.05。结论:在伊布利特合并低钾低镁的情况下才易诱发Tdp,电解质正常时不...     

丹参酮ⅡA在兔离体心脏2型长QT综合征模型中的电生理作用研究

目的研究丹参酮ⅡA在家兔离体心脏2型长QT综合征(LQT2)模型中的电生理作用。方法选用8只新西兰兔(2.5~3.5 kg),采用Langendorff系统经主动脉进行灌流离体心脏,稳定后持续灌流80 nmol/L的E-403115 min制备LQT2模型。继以梯度浓度丹参酮ⅡA(1、3、10、30、60μmol/L)灌流,观察其对室性心律失常诱发率、QT间期,有效不应期(ERP)和左室内、外膜[从动作电位0相至复极完成90%的单相动作电位时程(MAPD90)]的影响。结果80 nmol/L E-4031能使家兔离体心脏的QT间期、左心室内膜MAPD90、ERP延长(与对照相比,P<0.01),室性心动过速诱发率为37.5%(3/8)。联合丹参酮ⅡA使用后,离体心脏的QT间期、左心室内外膜的MAPD90、ERP以浓度依赖的方式缩短,当灌流浓度≥10μmol/L,QT间期明显缩短(与单独使用E-4031相比,P<0.05),浓度≥30μmol/L,左心室内、外膜的MAPD90、ERP缩短有统计学意义(P<0.05);1、3、10、30、60μmol/L丹参酮ⅡA灌流后的室性心动过速诱发率为2/8、0/8、0/8、0/8、0/8,差异无统计学意义(P>0.05)。结论丹参酮ⅡA可显著缩短LQT2的QT间期、左心室内、外膜的MAPD90和ERP;室性心动过速诱发率呈下降趋势。     

钙调蛋白拮抗剂W-7抑制索他洛尔诱发离体兔心尖端扭转型室性心动过速

目的观察钙调蛋白拮抗剂W-7对离体兔心实验性尖端扭转型室性心动过速(TdP)的影响,并探讨其机制。方法采用Langendorff灌流技术,在三度房室传导阻滞和低钾(1．5mmol／L)、低镁(0．35mmol／L)的条件下,用索他洛尔(30μmol／L)灌流离体雌兔心脏,建立TdP模型。36只雌兔心脏随机分为索他洛尔组和W-7低浓度(20μmol／L)、中浓度(50μmol／L)、高浓度(100μmol／L)干预组,每组各9只兔。灌流全程同步记录不同起搏周长下的心电图和左室内、中、外三层心肌的单相动作电位复极时程,并观察各组QT间期、跨室壁心肌复极离散度(TDR)、早期后除极(EAD)和TdP的诱发率。结果索他洛尔逆频率依赖性延长兔QT间期和增大左室三层心肌TDR,并有较高的。EAD(100％)和TdP(78％)诱发率。W-7浓度依赖性地抑制EAD诱发率(20μmol／L为56％,50μmol／L为44％,100μmol／L为11％)和TdP诱发率(20μmol／L为44％,50μmol／L为22％,100μmol／L为11％),但对QT间期和TDR均无影响。结论抑制钙调蛋白活性能够抑制离体兔心实验性TdP的发生,这种作用主要通过抑制EAD的机制而非通过影响跨室壁复极异质性的机制来发挥。     

门冬氨酸钾镁对家兔缺血再灌注心肌室性心律失常的影响

目的观察门冬氨酸钾镁注射液对家兔缺血再灌注心肌室性心律失常的抑制作用并探讨其抗心律失常作用机制.方法30只家兔随机分为正常组、心肌缺血组和治疗组,每组10只, 制备兔左心室楔形心肌块.正常组持续灌流台氏液,心肌缺血组和治疗组灌流台氏液1 h后停灌0.5 h,造成心肌缺血,0.5 h后复灌台氏液并程序刺激诱发心律失常,治疗组复灌的台氏液中含有浓度为2.42 mg/L的门冬氨酸钾镁.采用浮置玻璃微电极法同步记录楔形心肌块内、外膜心肌细胞跨膜动作电位和跨壁心电图,观察正常组、心肌缺血组和治疗组再灌注0.5 h的QT间期和内、外膜心肌细胞跨膜动作电位时程以及跨室壁复极离散度(TDR),记录正常组、心肌缺血组和治疗组缺血再灌注时室性心律失常的诱发率.结果①心肌缺血组较正常组和治疗组TDR明显延长(P＜0.05),治疗组与正常组相比,TDR差异无统计学意义(P＞0.05).②正常组无一例发生心律失常、心肌缺血组和治疗组室性心律失常的发生率分别为90%(9/10)、10%(1/10),心肌缺血组和治疗组间差异有统计学意义(P＜0.05).结论门冬氨酸钾镁可改善再灌注心肌的各项异常的电生理指标,特别是减小TDR,并能够明显降低再灌注心肌室性心律失常的发生率.     

缝隙连接对心肌肥厚兔室性心律失常的影响

目的研究兔慢性压力超负荷模型中缝隙连接(G J)对室性心律失常的影响。方法30只兔随机分为假手术组(Sham组)、心肌肥厚组(LVH组)和抗心律失常肽组(AAP10组)。LVH组和AAP10组通过缩窄腹主动脉制备兔左室压力超负荷心肌肥厚模型,Sham组仅游离腹主动脉未进行缩窄。动物饲养3个月后制备兔左室楔形心肌块的灌注模型,Sham组和LVH组灌流台氏液,AAP10组灌流含AAP10的台氏液,记录不同起搏周长下容积心电图、跨室壁离散度(TDR)及刺激反应间期(SR I),并观察早期后除极(EAD)及室性心律失常的发生率。结果在不同频率起搏下,LVH组SR I和TDR与Sham组比较均明显增加(P<0.05)。而AAP10组的SR I和TDR与LVH组比较明显减小(P<0.05)。Sham组无1例诱发EAD和室性心律失常;在5 000 m s起搏时LVH组和AAP10组EAD的发生率分别为10/10、3/10,室性心律失常发生率分别为4/10,1/10,两组比较差异有显著性(P<0.05)。结论G J激动剂AAP10减轻了心肌肥厚时SR I的延长和TDR增加,相应的减少了EAD和室性心律失常的发生率。     

尼克酰胺腺嘌呤二核苷酸对兔快速心房起搏后心房有效不应期的影响

目的观察尼克酰胺腺嘌呤二核苷酸(NADH)对急性离体心房颤动模型心房肌有效不应期(AERP)的影响及部分通道mRNA的改变。方法选择新西兰大耳白兔24只,随机等分为正常对照组、起搏对照组、起搏/NADH组、起搏/NADH+Rotenone(NADH氧化还原酶拮抗剂)组。正常对照组和起搏对照组用普通台氏液灌流,起搏/NADH组用含NADH的台氏液灌流,起搏/NADH+Rotenone组用含NADH及Rotenone的台氏液灌流。监测起搏前后(正常对照组为灌流前后)AERP的变化。AERP检测完毕后,取右房心肌组织,行半定量逆转录-聚合酶链式反应RT-PCR测定肌浆网钙泵、L型Ca2+通道、Ryanod ine2型受体(RyR2)的相对表达。结果快速心房起搏1 h后,起搏对照组和起搏/NADH+Rotenone组AERP缩短,以起搏对照组变化最大;正常对照组和起搏/NADH组起搏前后无明显变化。同时,快速心房起搏使肌浆网钙泵和L型Ca2+通道表达下调,RyR2受体表达上调;起搏/NADH+Rotenone组L型Ca2+通道表达下调,RyR2表达上调而肌浆网钙泵的表达无明显改变;而起搏/NADH组各相关基因表达无明显改变。结论NADH能够抑制快速心房起搏时心肌的电重构,其作用可能是通过促进肌浆网钙泵基因的表达和抑RyR2介导的Ca2+释放来实现的。     

钾通道开放剂对离体兔心缺血再灌注损伤的保护作用

目的观察非选择性三磷酸腺苷敏感性钾(KATP)通道开放剂Pinacidil和线粒体型KATP(mitoKATP)通道开放剂Diazoxide预处理对高钾停跳离体兔心缺血再灌注损伤的保护作用,以及mitoKATP通道阻断剂5-hydroxydecanoic acid sodiumsalt(5HD)应用后其心肌保护作用的变化。方法采用离体兔心Langendorff灌注实验模型。离体兔心40只随机等分成5组(n=8):对照组(C组)、Pinacidil组(P组)、Diazoxide组(D组)、5HD Pinacidil组(HP组)和5HD Diazoxide组(HD组)。离体兔心用标准Thomas停搏液(4℃,K 16mmol/L)至心停跳,45min后再灌注20min,于心脏停跳前灌注药物15min,对比观察Pinacidil、Diazoxide及其与5HD合用时对再灌注后心功能及冠状动脉血流的影响以及再灌注末心肌超微结构、蛋白含量、脂质过氧化物丙二醛(MDA)以及腺苷酸含量的变化。结果再灌注后P组、D组、HP组心功能的恢复率均明显高于C组,心肌MDA的含量、蛋白的漏出量明显低于C组,超微结构观察损伤较轻;但HP组心功能的恢复要差于P组,心肌MDA的含量、蛋白的漏出量明显高于P组;HD组与C组各检测指标比较差异无统计学意义。结论Pinacidil(10μmol/L)和Diazoxide(30μmol/L)预处理对离体兔心缺血/再灌注心肌具有保护效果,且其保护效果可以部分被5HD所阻断,提示心肌mitoKATP通道可能是产生心肌保护作用的靶点之一。     

Optical Mapping of Drug-Induced Polymorphic Arrhythmias and Torsade de Pointes in the Isolated Rabbit Heart

Objectives. This study sought to 1) test the hypothesis that in the setting of bradycardia and drug-induced action potential prolongation, multiple foci of early afterdepolarizations (EADs) result in beat to beat changes in the origin and direction of the excitation wave front and are responsible for polymorphic arrhythmias; and 2) determine whether EADs may initiate nonstationary reentry, giving rise to the typical torsade de pointes (TDP) pattern.Background. In the past, it has been difficult to associate EADs or reentry with the undulating electrocardiographic (ECG) patterns of TDP.Methods. A voltage-sensitive dye was used for high resolution video imaging of electrical waves on the epicardial and endocardial surface of the Langendorff-perfused rabbit heart. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atrioventricular node.Results. Perfusion of low potassium chloride Tyrode solution plus quinidine led to prolongation of the action potential and the QT interval. Eventually, EADs and triggered activity ensued, giving rise to intermittent episodes of polymorphic arrhythmia. In one experiment, triggered activity was followed by a long episode of vortex-like reentry with an ECG pattern characteristic of TDP. However, in most experiments, focal activity of varying origins and propagation patterns was observed. Triggered responses also showed varying degrees of local block. Similar results were obtained with E-4031. Burst pacing both at control conditions and in the presence of quinidine consistently led to vortex-like reentry whose ECG pattern resembled TDP. However, the cycle length of the arrhythmia with quinidine was longer than that for control ([mean ± SEM] 194 ± 12 vs. 132 ± 8 ms, p < 0.03).Conclusions. Drug-induced polymorphic ventricular arrhythmias may result from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, burst pacing–induced polymorphic tachycardia in the presence or absence of drugs is the result of nonstationary reentrant activity.(J Am Coll Cardiol 1997;29:831–42)     

Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A (long QT3) mice

OBJECTIVE: It has been suggested that both pacing and treatment with mexiletine may reduce torsade de pointes (TdP) arrhythmias in patients with long QT syndrome 3 (LQT3), but it is not fully understood how these interventions could prevent TdP. We therefore studied the effects of pacing and mexiletine in mice with a heterozygous knock-in DeltaKPQ SCN5A(Delta/+) deletion (SCN5A-Tg), a murine LQT3 model. METHODS: Three right and left ventricular monophasic action potentials (MAPs) were simultaneously recorded in Langendorff-perfused hearts of SCN5A-Tg and wild type (WT) littermates. AV block was induced, and pacing was performed at baseline and during mexiletine infusion (4 microg/ml). MAP recordings were analysed for action potential duration (APD), APD dispersion, and early afterdepolarisations (EADs) and related to spontaneous arrhythmias. RESULTS: After inducing AV block, SCN5A-Tg hearts were bradycardic [SCN5A-Tg 532+/-60 vs. WT 284+/-48 ms cycle length (CL, mean+/-S.E.M., P<0.05(*))]. EADs occurred in 16/18, and polymorphic ventricular tachycardia (pVT) in 11/18 SCN5A-Tg but not in 19 WT. SCN5A-Tg had longer APD than WT hearts*. At CL of 200 ms and longer, APD dispersion was higher in SCN5A-Tg [dispersion (APD70): 12+/-3 ms vs. 5+/-2 ms at CL=200 ms*], and increased to 35+/-4 ms* directly prior to pVT episodes. Sudden rate accelerations initially increased APD dispersion due to EADs and APD alternans in SCN5A-Tg, but pacing then reduced APD dispersion. Pacing suppressed (n=9/9) and prevented (n=49/50) pVT. Mexiletine shortened APD at long CL*, and suppressed pVT (n=4/5*), but did not prevent pVT during normal rhythm. CONCLUSIONS: Bradycardia, increased dispersion of APD and EADs provoke ventricular ectopy and pVT in SCN5A-Tg hearts. Ventricular pacing reduces APD dispersion, suppresses EADs and prevents pVT in SCN5A-Tg hearts. These effects provide a pathophysiological rationale for pacing in LQT3.     

Early Afterdepolarizations in the Familial Long QTU Syndrome

Early Afterdepolarizations in Long QTU Syndrome. Torsade de pointes-induced syncopal episodes were almost invariably precipitated by emotional stress or menses in a 17-year-old female. U wave accentuation occurred during periods of heigbtened sympathetic tone. To document tbe role of early afterdepolarizations (EADs), monopbasic action potentials were recorded during ventricular extrasystoles and torsade de pointes occurring spontaneously and induced by ventricular pacing in tbe control state and after intravenous lidocaine. The effects of verapamil, propranolol, and epinephrine were observed. Our data show that: (1) EADs may play a significant role in the genesis of familial long QTU syndrome and torsade de pointes; (2) a faster ventricular pacing rate for a longer duration is related to tbe emergence of subsequent pause-dependent EADs, U waves, and torsade de pointes; (3) atrial pacing with Wenckebach block can provoke large postpause U waves, thus eliciting dual ventricular tachycardia; (4) EADs are enhanced by epinepbrine infusion in the absence of pause; and (5) EAD-triggered firing is inhibited by verapamil and propranolol but not by lidocaine. (J Cardiovasc Electrophysiol. Vol. 3, pp. 431–436, October 1992)     

Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3

BACKGROUND: Congenital and acquired long QT syndrome (LQTS) are caused by abnormalities of ionic currents underlying ventricular repolarization. For a better understanding of the mechanisms by which functional electrical instability at the level of the whole heart leads to torsade de pointes (TdP), a novel model of LQT3 was developed and the role of transmural dispersion of repolarization for the development of proarrhythmia was evaluated. METHODS AND RESULTS: In 11 Langendorff-perfused rabbit hearts, veratridine (0.1-0.5 microM), an inhibitor of sodium channel inactivation, led to a concentration-dependent increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p<0.05) and thereby mimicked LQT3. Veratridine reproducibly induced early afterdepolarizations (EADs) and TdP after lowering potassium concentration. In bradycardic (AV-blocked) hearts, the increase in MAP duration showed marked regional differences. It was significantly more pronounced on the left endocardium as compared to left or right epicardium. This resulted in a significant increase in dispersion of repolarization (24% at 0.1 microM, 92% at 0.25 microM, 208% at 0.5 microM; p<0.01). Left ventricular transmural dispersion of repolarization increased significantly more than interventricular dispersion (104 to 33 ms at 0.5 microM veratridine; p<0.05). CONCLUSION: By inhibition of sodium channel inactivation, veratridine mimics LQT3 in this intact heart model. In bradycardic, hypokalemic hearts, it reproducibly induced EADs and TdP in the setting of significantly increased left ventricular transmural dispersion of repolarization. Based on these experimental data, reduction of transmural dispersion of repolarization may be considered an important target for the prevention of TdP in patients with LQT3.     

Additive Proarrhythmic Effect of Combined Treatment with QT-Prolonging Agents

Drug combinations may elevate the risk of proarrhythmia. The aim of the present study was to investigate whether combinations of non-cardiovascular agents induce an additive increase in the proarrhythmic risk. In 12 female rabbit hearts, a drug combination of cotrimoxazole (300 µM), ondansetron (5 µM) and domperidone (1 µM) was infused after obtaining baseline data. In another 13 hearts, a combination of cotrimoxazole (300 µM), ondansetron (5 µM) and erythromycin (300 µM) was infused. Monophasic action potentials and ECG displayed a significant QT prolongation in all groups. This was accompanied by a significant increase in action potential duration. Of note, addition of each drug resulted in a further increase in the QT interval. Furthermore, a significant elevation of spatial dispersion of repolarization was observed. Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations and torsade de pointes (TDP) in both study groups. Under baseline conditions, no episodes of TDP recorded. After administration of the first agent, TDP occurred in 5 of 12 hearts (37 episodes) and 5 of 13 hearts (26 episodes), respectively. After additional infusion of the second drug, TDP were recorded in 7 of 12 hearts (55 episodes) and 8 of 13 hearts (111 episodes). After additional infusion of the third drug, TDP occurred in 11 of 12 hearts (118 episodes) and 9 of 13 hearts (88 episodes). Combined treatment with several non-cardiovascular QT-prolonging agents resulted in a remarkable occurrence of proarrhythmia. An additive and significant prolongation of cardiac repolarization combined with an increased spatial dispersion of repolarization represents the underlying electrophysiological mechanism.     

大鼠心房肌电生理特性的增龄性变化

目的探讨年龄对心房肌单相动作电位(MAP)和有效不应期(ERP)的影响,及其与心房颤动(房颤)的关系。方法选取Wistar大鼠40只分为青年组、成年组、中年组和老年组4组。Langendorff体外灌流心脏。分别测量各组心房肌在400ms刺激周长下MAP复极到90%、50%及20%时的时程(MAPD90、MAPD50、MAPD20)和ERP,以及其他不同刺激周长下的MAPD。结果在400ms刺激周长下,4组大鼠右心房肌MAPD90随年龄增长而逐渐延长〔(75±5)(、123±8)(、140±11)和(140±14)ms,均为P<0.01〕;而左心房肌青年组至中年组延长分别为〔(60±4),(120±3),(139±7)〕,老年组缩短〔(102±14)ms,均为P<0.01〕。心房肌ERP的增龄性变化规律与MAPD90相同。刺激周长从400ms缩短到250ms,右心房肌MAPD90缩短程度从青年组到老年组逐渐增加;左心房肌以老年组缩短程度最小。结论左右心房肌电生理特性增龄性变化规律不同。老年期心房电生理变化可能有利于房颤的发生。     

The Effect of Flunarizine and Ryanodine on Acquired Torsades de Pointes Arrhythmias in the Intact Canine Heart

Flunarizine and Ryanodine in Acquired TdP. Introduction: Ryanodine, a specific blocker of the Ca²⁺ release channel of the sarcoplasmic reticulum, and flunarizine, a[Ca²⁺], overload blocker, possess antiarrhythmic effects against delayed after depolarizations (DADs) and DAD-dependent arrhythmias. In vitro controversy exists about their effect on early after depolarizations (EADs): no effect was reported on cesium-induced EADs, while ryanodine did prevent EADs induced by isoproterenol. To study the possible role of intracellular Ca²⁺ overload in acquired EAD-dependent torsades de pointes (TdP) arrhythmias, we tested the effects of flunarizine and ryanodine in our animal model of TdP. Methods and Results: Anaesthetized dogs with chronic AV block received d-sotalol or almokalant followed by pacing. A subset of dogs with reproducible TdP (≥ 3 times) were selected to receive flunarizine (2 mg/kg per 2 min) or ryanodine (10 μg/kg per 10 min). After dsotalol, TdP was induced at a mean cycle length of the idioventricular rhythm (CL-IVR) of 2070 ± 635 msec and a QT(U) interval of 535 ± 65 msec. Induction of TdP was prevented by flunarizine in all experiments (8/8): electrophysiologically this was associated with a decrease in CL-IVR, QT(U), and QT_c interval (390 ± 100 to 320 ± 45, P < 0.05). Ryanodine prevented TdP induction in 4 of 5 experiments and decreased the CL-IVR, QT(U), and the QT_c interval from 385 ± 75 to 320 ± 20 msec (P < 0.05). Both drugs also suppressed the almokalant-induced EADs and related ectopic activity. This antiarrhythmic action corresponded with the inability to reinduce TdP by pacing. Conclusions: Blockade of the Ca²⁺ release channel of the sarcoplasmic reticulum by ryanodine or the reduction of [Ca²⁺] overload by flunarizine prevents induction of EAD-dependent acquired TdP arrhythmias, suggesting a role for [Ca²⁺]_i overload in acquired TdP.     

大鼠左心房肌单相动作电位的增龄性变化

目的　研究年龄对大鼠左心房肌单相动作电位(monophasicactionpotential,MAP)的影响。方法　选取实验用Wistar大鼠4 0只,按出生年龄分为青年组、成年组、中年组及老年组,每组10只。体外Langendorff灌流心脏,右心室刺激。分别记录各组左心房肌在4 0 0ms刺激周长下动作电位复极到90 %、5 0 %及2 0 %时的单相动作电位时程(MAPD90 )、MAPD50 、MAPD2 0 和心房有效不应期,以及在不同刺激周长下的MAPD90 、MAPD50 、MAPD2 0 。结果　MAPD各时相和有效不应期都随着年龄的增加而出现延长(P <0 .0 1) ;但老年组缩短。在同一年龄组中,刺激频率增加使动作电位时程都相应缩短,以MAPD90 明显;中年组MAPD改变明显。结论　年龄是影响心脏电活动重要的独立因素之一。     

链霉素对心肌梗死大鼠离体心脏牵张时心律失常的影响

目的探讨链霉素对心肌梗死(简称MI)大鼠离体心脏牵张时心律失常的影响。方法36只wistar大鼠随机分为正常对照组、链霉素组、MI组、MI+链霉素组。离体心脏经Langendorff灌流后,通过改变水囊容积,以△V=0.1,0.2,0.3ml对心室牵张5s,观察牵张效应30s,记录90%单相动作电位时程(MAPD90)、室性早搏(PVB)及室性心动过速(VT)的次数。结果牵张使正常对照组及MI组MAPD90显著延长(P<0.05或0.01),其中MI组在相应牵张幅度下其MAPD90增加更为显著(与正常对照组比较,P<0.01;如△V=0.3ml,从63.2±4.95ms到55.67±4.39ms)。链霉素对基础状态下MAPD90无影响(P>0.05),但可使牵张后已延长的MAPD90显著缩短(P均<0.05;如MI组与MI+链霉素组,△V=0.2ml,从58.09±4.27ms到53.1±3.64ms)。正常及MI组PVB和VT发生率随△V的增加而增加,且后者高于前者。链霉素使两组PVB发生率显著下降,并可显著抑制VT的发生(P<0.005)。结论MI后牵张更有助于恶性心律失常的产生和维持,链霉素可以明显抑制上述现象的发生。     

Torsade de pointes induced by terfenadine in a patient with long QT syndrome

Torsade de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although torsade de pointes is found in many clinical settings, it is mostly drug induced. Similar problems have been described with nonsedating H₁-receptor antagonists, such as astemizole and terfenadine. Terfenadine is a widely used antihistamine. The authors report a case of torsade de pointes in a patient with a possible congenital sporadic form of QT interval prolongation who was receiving a therapeutic dose of terfenadine.