THE WAVELET ANALYSIS OF EVOKED POTENTIALS

ＴＨＥＷＡＶＥＬＥＴＡＮＡＬＹＳＩＳＯＦＥＶＯＫＥＤＰＯＴＥＮＴＩＡＬＳＴＨＥＷＡＶＥＬＥＴＡＮＡＬＹＳＩＳＯＦＥＶＯＫＥＤＰＯＴＥＮＴＩＡＬＳＬｉＧｕａｎ；ＤａｚｏｎｇＪｉａｎｇ（ＢｉｏｍｅｄｉｃａｌＥｎｇｉｎｅｅｒｉｎｇＲｅｓｅａｒｃｈｉｎｓｔｉ...     

苯海索对豚鼠乳头状肌动作电位、收缩力及兔窦房结细胞动作电位的影响

苯海索（ＴＨＰ）１０、５０、１００μｍｏｌ／Ｌ抑制豚鼠乳头状肌收缩力（Ｆｃ），缩短动作电位时程（ＡＰＤ）和有效不应期（ＥＲＰ），抑制最大去极化速率（Ｖｍａｘ）；ＴＨＰ５０μｍｏｌ／Ｌ对Ｖｍａｘ的抑制呈频率依赖性。ＴＨＰ５０、１００μｍｏｌ／Ｌ可降低其ＡＰＡ，缩短其ＥＲＰ，ＴＨＰ可对抗ＢａｙＫ８６４４增强Ｆｃ，延长ＥＲＰ、ＡＰＤ的作用。ＴＨＰ５０μｍｏｌ／Ｌ可抑制哇巴因（Ｏｕａ）诱发的振荡电位和触发活动。ＴＨＰ５、１０、５０μｍｏｌ／Ｌ抑制兔窦房结细胞动作电位的动作电位幅度（ＡＰＡ），４相除极化速率（ＳＰ＿４）和Ｖｍａｘ，延长窦性周氏（ＳＣＬ）。结果提示ＴＨＰ对Ｃａ￣（２＋）和Ｎａ￣（２＋）的跨膜转运均有抑制作用。     

EFFECT OF SUSPENDING MEDIUM VISCOSITY ONORIENTATION AND DEFORMATION OF RBCs IN A SHEAR FlOW FIELD

ＥＦＦＥＣＴＯＦＳＵＣＰＥＮＤＩＮＧＭＥＤＩＵＭＶＩＳＣＯＳＩＴＹＯＮＯＲＩＥＮＴＡＴＩＯＮＡＮＤＤＥＦＯＲＭＡＴＩＯＮＯＦＲＢＣＳＩＮＡＳＨＥＡＲＦｌＯＷＦＩＥＬＤＷｅｎＺｏｎｇ－ｙａｏ，ＭａＷｅｉｙｕａｎ，ＧａｏＴｉｅ，ＳｕｎＤａｇｏｎｇＤｅｐａ...     

一氧化氮合酶阻断剂对豚鼠耳蜗基底膜振动速度的影响

目的：观察Ｎ－甲基－左旋精氨酸（ＮＮＡ）对基底膜振动速度（ＢＭＶ）的影响,了解一氧化氮（ＮＯ）对耳蜗外毛细胞（ＣＯＨＣｓ）的作用。方法：杂色豚鼠２５只,麻醉、手术准备后用１．６ｍｍｏｌ／Ｌ的Ｌ－ＮＮＡ８μＬ行耳蜗底圈鼓阶内灌注,测试ＢＭＶ、听神经复合动作电位（ｃＡＰ）、蜗内电位（ＥＰ）,记录用直流电脉冲诱发的ＢＭＶ。结果：蜗内灌注Ｌ－ＮＮＡ后,ＢＭＶ大约提高了３倍,耳蜗微音器电位振幅略有下降,而Ｅ     

虎杖甙对正常人血管平滑肌细胞内钙和膜电位的调节作用

目的和方法：观察虎杖甙（ＰＤ）对人脐带动脉平滑肌细胞（ＶＳＭＣ）内游离钙、细胞膜电位的变化,以探讨ＰＤ对血管平滑肌的调节机制。用Ｆｌｕｏ－３－ＡＭ、ＤｉＢＡＣ４（３）标记培养的ＶＳＭＣ,在激光共聚焦显微镜上测定细胞内游离钙和膜电位变化。结果：给ＰＤ（０５ｍｍｏｌ／Ｌ）１０ｍｉｎ后,ＶＳＭＣ内游离钙浓度升高５６％±５６％。当ＰＤ加入前用维拉帕米和ＥＧＴＡ预处理后,则游离钙不再升高;ＥＧＴＡ和肝素预处理也抑制ＰＤ的升钙作用,而ＥＧＴＡ和普鲁卡因预处理则使细胞内钙显著升高。ＰＤ还可使ＶＳＭＣ膜电位去极化,加入钠通道阻断剂河豚毒素（２５μｍｏｌ／Ｌ）可完全阻断ＰＤ的去极化作用：加甲氰咪胍、维拉帕米、优降糖和利及丁预处理不能阻断ＰＤ去极化作用。结论：：ＰＤ可通过细胞外钙内流来增加细胞内游离钙浓度,并促进细胞外钠离子内流而导致细胞去极化     

STUDY ON SOLUBILITY OF APATITE CERAMIES IN VITRO

ＳＴＵＤＹＯＮＳＯＬＵＢＩＬＩＴＹＯＦＡＰＡＴＩＴＥＣＥＲＡＭＩＥＳＩＮＶＩＴＲＯＳＴＵＤＹＯＮＳＯＬＵＢＩＬＩＴＹＯＦＡＰＡＴＩＴＥＣＥＲＡＭＩＥＳＩＮＶＩＴＲＯＬ．ＮｉｎｇＭ．Ｘｕｅ（ＳｈａｎｇｈａｉＳｅｃｏｎｄＭｅｄｉｃａｌＵｎｉｖｅｒｓｉｔｙ...     

DEVELOPED IMPROVED AND CLINICAL APPLICATION OF BIPOLAR HIP PROSTHESIS—2—13 YEARS FOLLOW—UP

ＤＥＶＥＬＯＰＥＤＩＭＰＲＯＶＥＤＡＮＤＣＬＩＮＩＣＡＬＡＰＰＬＩＣＡＴＩＯＮＯＦＢＩＰＯＬＡＲＨＩＰＰＲＯＳＴＨＥＳＩＳ—２—１３ＹＥＡＲＳＦＯＬＬＯＷ—ＵＰＤＥＶＥＬＯＰＥＤＩＭＰＲＯＶＥＤＡＮＤＣＬＩＮＩＣＡＬＡＰＰＬＩＣＡＴＩＯＮＯＦＢＩＰＯ...     

IL-4 和sCD40 L 协同增强体外IgE 的生成

应用 Ｅ Ｌ Ｉ Ｓ Ａ 和 Ｃ Ａ Ｐ 变应原系统, 检测２４ 例对屋尘螨过敏的Ⅰ型超敏反应患者血浆中总 Ｉｇ Ｅ 和特异性 Ｉｇ Ｅ 的水平,以及外周血单个核细胞（ Ｐ Ｂ Ｍ Ｃ） 在 Ｉ Ｌ ４ 、可溶性 Ｃ Ｄ４０ 配体（ｓ Ｃ Ｄ４０ Ｌ） 作用下, 其培养上清液中总 Ｉｇ Ｅ 和特异性 Ｉｇ Ｅ 的水平。结果表明： （１ ） Ⅰ型超敏反应患者血浆中 Ｉｇ Ｅ 水平比正常组高（ Ｐ＜ ００１ ） ; （２ ） 在 Ｉ Ｌ ４ 和ｓ Ｃ Ｄ４０ Ｌ 共同作用下, Ｐ Ｂ Ｍ Ｃ 培养上清液中总 Ｉｇ Ｅ 和特异性 Ｉｇ Ｅ 的水平比 Ｉ Ｌ ４ 或ｓ Ｃ Ｄ４０ Ｌ单独作用下明显升高（ Ｐ＜ ００１ ） 。提示 Ｉｇ Ｅ 的生成不仅需要 Ｉ Ｌ ４ 的作用, 还需要 Ｔ、 Ｂ 细胞接触介导的信号传导或 Ｔ 细胞释放的细胞因子作用, 而ｓ Ｃ Ｄ４０ Ｌ 就是其中的重要因子之一。     

CLINICAL SIMULATED EXPERIMENT ON THE SYNDROMI STANDARDS OF PULMONARY SYSTEM DISEASES

ＣＬＩＮＩＣＡＬＳＩＭＵＬＡＴＥＤＥＸＰＥＲＩＭＥＮＴＯＮＴＨＥＳＹＮＤＲＯＭＩＳＴＡＮＤＡＲＤＳＯＦＰＵＬＭＯＮＡＲＹＳＹＳＴＥＭＤＩＳＥＡＳＥＳＭｕｌｉｎＸｕＱｉｏｕｑｉｎＷａｎｇ（ＨｕｂｅｉＡｃａｄｅｍｙｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅ...     

脂质过氧化在老化大鼠急性胆源性肝细胞线粒体损害中的作用及维生素E的影响

目的：探讨脂质过氧化在老化大鼠胆源性肝细胞线粒体受损中及维生素Ｅ（ＶＥ）的保护作用。结果：老化大鼠非ＶＥ处理组（ＮＶＥＧ）肝细胞线粒体丙二醛（ＭＤＡ）含量明显高于非老化组，超氧化物歧化酶（ＳＯＤ）和谷胱甘肽过氧化物酶（ＧＰＤ）活性明显低于非老化组，过氧化氢酶（ＣＡＴ）无明显变化。１８和２４月龄ＶＥ处理组（ＶＥＧ）ＭＤＡ显著低于ＮＶＥＧ，ＳＯＤ和ＧＰＤ显著高于ＮＶＥＧ，并以１８月龄组为明显。急性梗阻性左肝胆管炎（ＡＯＬＨ）后ＭＤＡ水平明显高于对照组，间接致伤肝叶（ＩＡＬ）较直接致伤肝叶（ＤＡＬ）为明显；ＩＡＬ线粒体ＳＯＤ和ＣＡＴ活性均显著高于对照组，ＤＡＬ显著降低；各叶ＧＰＤ活性均显著低于对照组，ＩＡＬ和ＤＡＬ均无显著差别；以上改变以２４月龄组为明显。各月龄ＶＥＧＡＯＬＨ２４ｈ时ＩＡＬＭＤＡ含量明显低于ＮＶＥＧ；１８月龄ＶＥＧＡＯＬＨ后ＳＯＤ水平均明显高于ＮＶＥＧ；各月龄ＶＥＧ组ＡＯＰＨ后ＧＰＤ和ＣＡＴ活性与ＮＶＥＧ比较均无明显差异。结论：脂质过氧化是老化大鼠胆源性肝细胞线粒体受损的重要机制，ＶＥ具有明显的保护作用。     

Prolonged intra-myocardial growth hormone administration ameliorates post-infarction electrophysiologic remodeling in rats

Experimental studies indicate improved ventricular function after treatment with growth hormone (GH) post-myocardial infarction, but its effect on arrhythmogenesis is unknown. Here, we assessed the medium-term electrophysiologic remodeling after intra-myocardial GH administration in (n?=?33) rats. GH was released from an alginate scaffold, injected around the ischemic myocardium after coronary ligation. Two weeks thereafter, ventricular tachyarrhythmias were induced by programmed electrical stimulation. Monophasic action potentials were recorded from the infarct border, coupled with evaluation of electrical conduction and repolarization from a multi-electrode array. The arrhythmia score was lower in GH-treated rats than in alginate-treated rats or controls. The shape and the duration of the action potential at the infarct border were preserved, and repolarization–dispersion was attenuated after GH; moreover, voltage rise was higher and activation delay was shorter. GH normalized also right ventricular parameters. Intra-myocardial GH preserved electrical conduction and repolarization–dispersion at the infarct border and decreased the incidence of induced tachyarrhythmias in rats post-ligation. The long-term antiarrhythmic potential of GH merits further study.     

Rate dependence of mechanically induced electrophysiological changes in right ventricle of anaesthetized lambs during pulmonary artery occlusion

AIM: Mechanically induced early afterdepolarization (EAD) is morphologically similar but different in the mechanisms with drug-induced EAD, which lead to arrhythmia. Pacing suppresses the drug-induced EAD and arrhythmia, however the effect of pacing on mechanically induced EAD and arrhythmia is not clear. This study addressed this issue in right ventricle (RV) of anaesthetized lambs. METHODS: Six lambs were anaesthetized, and their hearts exposed. Nine monophasic action potential (MAP) electrodes were placed on RV apex, outflow and inflow regions, and recorded before, during, and after a 10 s occlusion of pulmonary artery at a number of pacing rates. RESULTS: Pacing significantly reduced the baseline MAP duration at 90% repolarization (MAPD90), decreased the reduction of MAPD at early repolarization at the peak of occlusion. Nonetheless, the percentage of reduction was not significantly different among them. Pacing was able to reduce the frequencies, size of mechanically induced EADs. MAPD90 at the peak of occlusion was all shortened during pacing rather than some lengthened at intrinsic rate. Therefore, the dispersion of MAPD90 at the peak of occlusion reduced from 86 +/- 6 ms at intrinsic rate to 42 +/- 4 ms at 120 beats min-1, 38 +/- 3 ms at 150 beats min-1 and 26 +/- 3 ms at 170 beats min-1. Ultimately, pacing reduced/suppressed mechanically induced premature ventricular beats. These alterations were inversely related to heart rates. CONCLUSION: Pacing reduces/suppresses both stretch-induced EADs and arrhythmia. These modulations are remarkably similar to those on other EADs by the pacing.     

Electrophysiological determinants of hypokalaemia‐induced arrhythmogenicity in the guinea‐pig heart

Aim: Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia‐induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea‐pig heart preparations. Methods: Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume‐conducted electrocardiogram (ECG) during steady‐state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results: Hypokalaemic perfusion (2.5 mm K⁺ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re‐excitation. Hypokalaemia increased the RV‐to‐LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD₉₀ and refractoriness across the LV wall. As determined by local activation time recordings, the LV‐to‐RV transepicardial conduction and the LV transmural (epicardial‐to‐endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion: These findings suggest that hypokalaemia‐induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re‐excitation, amplified RV‐to‐LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea‐pig heart.     

Role of Ca2+-activated Cl- current during proarrhythmic early afterdepolarizations in sheep and human ventricular myocytes

OBJECTIVES: The proarrhythmic early afterdepolarizations (EADs) during phase-2 of the cardiac action potential (phase-2 EADs) are associated with secondary Ca2+-release of the sarcoplasmic reticulum. This makes it probable that the Ca2+-activated Cl- current [ICl(Ca)] is present during phase-2 EADs. Activation of ICl(Ca) during phase-2 of the action potential will result in an outwardly directed, repolarizing current and may thus be expected to prevent excessive depolarization of phase-2 EADs. The present study was designed to test this hypothesis. METHODS AND RESULTS: The contribution of ICl(Ca) during phase-2 EADs was studied in enzymatically isolated sheep and human ventricular myocytes using the patch-clamp methodology. EADs were induced by a combination of a low stimulus frequency (0.5 Hz) and exposure to 1 microm noradrenaline. In sheep myocytes, the ICl(Ca) blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.5 mm) abolished phase-1 repolarization of the action potential in all myocytes tested. This indicates that ICl(Ca) is present in all sheep myocytes. However, DIDS had no effect on phase-2 EAD characteristics. In human myocytes, DIDS neither affected phase-1 repolarization nor phase-2 EAD characteristics. CONCLUSION: In sheep ventricular myocytes, but not in human ventricular myocytes, ICl(Ca) contributes to phase-1 repolarization of the action potential. In both sheep and human myocytes, ICl(Ca) plays a limited role during phase-2 EADs.     

TNF‐α hyperpolarizes membrane potential and potentiates the response to nicotinic receptor stimulation in cultured rat myenteric neurones

Aim: Mechanically induced early afterdepolarization (EAD) is morphologically similar but different in the mechanisms with drug‐induced EAD, which lead to arrhythmia. Pacing suppresses the drug‐induced EAD and arrhythmia, however the effect of pacing on mechanically induced EAD and arrhythmia is not clear. This study addressed this issue in right ventricle (RV) of anaesthetized lambs. Methods: Six lambs were anaesthetized, and their hearts exposed. Nine monophasic action potential (MAP) electrodes were placed on RV apex, outflow and inflow regions, and recorded before, during, and after a 10 s occlusion of pulmonary artery at a number of pacing rates. Results: Pacing significantly reduced the baseline MAP duration at 90% repolarization (MAPD₉₀), decreased the reduction of MAPD at early repolarization at the peak of occlusion. Nonetheless, the percentage of reduction was not significantly different among them. Pacing was able to reduce the frequencies, size of mechanically induced EADs. MAPD₉₀ at the peak of occlusion was all shortened during pacing rather than some lengthened at intrinsic rate. Therefore, the dispersion of MAPD₉₀ at the peak of occlusion reduced from 86 ± 6 ms at intrinsic rate to 42 ± 4 ms at 120 beats min⁻¹ , 38 ± 3 ms at 150 beats min⁻¹ and 26 ± 3 ms at 170 beats min⁻¹. Ultimately, pacing reduced/suppressed mechanically induced premature ventricular beats. These alterations were inversely related to heart rates. Conclusion: Pacing reduces/suppresses both stretch‐induced EADs and arrhythmia. These modulations are remarkably similar to those on other EADs by the pacing.     

Electrophysiological changes in rat ventricular and atrial myocardium at different stages of experimental diabetes

Action potential configuration in ventricular and atrial myocardium, as well as rate-dependent changes in ventricular action potential duration (APD) were studied and compared in healthy and diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 65 mg kg^–1 i.v.). Conventional microelectrode techniques were applied to record action potentials after the establishment of diabetes (2, 6, 10 and 18 weeks after STZ-treatment). Untreated age-matched animals were used as controls. Both depolarization and repolarization were significantly retarded following STZ-treatment. However, the time course of development of diabetic changes in atrial and ventricular myocardium was different. APD was significantly lengthened from week 2 of diabetes in ventricular, but only from week 6 in atrial preparations. In atrial myocardium, lengthening of APD was more pronounced at early rather than late phases of repolarization. The maximum rate of depolarization (V_max) was significantly reduced from the 6th week of diabetes in both preparations. No differences were observed in action potential amplitude (except at week 18) and in the resting membrane potential in diabetic rats. Diabetic ventricular preparations showed a positive APD-frequency relationship at any level of repolarization, in contrast to control muscles, where APD₂₅ and APD₅₀ values lengthened. But APD₇₅ and APD₉₀ values were not changed significantly with increase in the pacing frequency. The results indicate that development of diabetic alterations are not fully identical in atrial and ventricular myocardium of the rat, probably owing to differences in density and kinetics of ionic currents responsible for atrial and ventricular action potentials.     

Role of Ca2+‐activated Cl− current during proarrhythmic early afterdepolarizations in sheep and human ventricular myocytes

Objectives: The proarrhythmic early afterdepolarizations (EADs) during phase‐2 of the cardiac action potential (phase‐2 EADs) are associated with secondary Ca²⁺‐release of the sarcoplasmic reticulum. This makes it probable that the Ca²⁺‐activated Cl^? current [I_Cl(Ca)] is present during phase‐2 EADs. Activation of I_Cl(Ca) during phase‐2 of the action potential will result in an outwardly directed, repolarizing current and may thus be expected to prevent excessive depolarization of phase‐2 EADs. The present study was designed to test this hypothesis. Methods and Results: The contribution of I_Cl(Ca) during phase‐2 EADs was studied in enzymatically isolated sheep and human ventricular myocytes using the patch‐clamp methodology. EADs were induced by a combination of a low stimulus frequency (0.5 Hz) and exposure to 1 μm noradrenaline. In sheep myocytes, the I_Cl(Ca) blocker 4,4′‐diisothiocyanostilbene‐2,2′‐disulfonic acid (DIDS, 0.5 mm ) abolished phase‐1 repolarization of the action potential in all myocytes tested. This indicates that I_Cl(Ca) is present in all sheep myocytes. However, DIDS had no effect on phase‐2 EAD characteristics. In human myocytes, DIDS neither affected phase‐1 repolarization nor phase‐2 EAD characteristics. Conclusion: In sheep ventricular myocytes, but not in human ventricular myocytes, I_Cl(Ca) contributes to phase‐1 repolarization of the action potential. In both sheep and human myocytes, I_Cl(Ca) plays a limited role during phase‐2 EADs.     

镁对在体兔缺血—再灌心脏的电生理效应

本实验通过结扎兔冠状动脉左室支复制动脉缺血－再灌注模型，应用心外膜接触电极记录单相动作电位，观察后除极电位在再灌注性心律失常中及镁离子的拮抗作用。结果表明，再灌性心律失常的５２．６％与早期后去极化有关。硫酸镁可终止及预防ＲＡ，对再灌中出现触发活动有抑制作用。     

Dendritic potassium channels in hippocampal pyramidal neurons

Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 μm of the apical dendrites, so that action potentials recorded farther than 200 μm from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K⁺ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.     

Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome

Enhanced dispersion of repolarization has been proposed as an important mechanism in long QT related arrhythmias. Dispersion can be dynamic and can be augmented with the occurrence of spatially out-of-phase action potential duration (APD) alternans (discordant alternans; DA). We investigated the role of tissue heterogeneity in generating DA using a novel transgenic rabbit model of type 2 long QT syndrome (LQT2). Littermate control (LMC) and LQT2 rabbit hearts ( n = 5 for each) were retrogradely perfused and action potentials were mapped from the epicardial surface using di-4-ANEPPS and a high speed CMOS camera. Spatial dispersion (ΔAPD and Δslope of APD restitution) were both increased in LQT2 compared to LMC (ΔAPD: 34 ± 7 ms vs. 23 ± 6 ms; Δslope:1.14 ± 0.23 vs. 0.59 ± 0.19). Onset of DA under a ramp stimulation protocol was seen at longer pacing cycle length (CL) in LQT2 compared to LMC hearts (206 ± 24 ms vs. 156 ± 5 ms). Nodal lines between regions with APD alternans out of phase from each other were correlated with conduction velocity (CV) alternation in LMC but not in LQT2 hearts. In LQT2 hearts, larger APD dispersion was associated with onset of DA at longer pacing CL. At shorter CLs, closer to ventricular fibrillation induction (VF), nodal lines in LQT2 ( n = 2 out of 5) showed persistent complex beat-to-beat changes in nodal line formation of DA associated with competing contribution from CV restitution and tissue spatial heterogeneity, increasing vulnerability to conduction block. In conclusion, tissue heterogeneity plays a significant role in providing substrate for ventricular arrhythmia in LQT2 rabbits by facilitating DA onset and contributing to unstable nodal lines prone to reentry formation.