儿茶酚抑素对慢性心力衰竭大鼠室性心律失常的影响

 目的：探讨儿茶酚抑素(CST)治疗对慢性心力衰竭(CHF)大鼠室性心律失常(VA)的影响。方法：雄性SD大鼠51只，随机分为对照(CTL)组(n=17)和CHF组(n=34)。CHF组给予连续7 d注射异丙肾上腺素(ISO) (5 mg·kg-1·d-1, ip)，CTL组则用生理盐水作为对照 (1 mL·kg-1·d-1, ip)，造模结束2周后，进一步将CHF组再随机分为未治疗组(n=17)和CHF治疗组(CST组)(n=17)。治疗组给予连续3周注射CST(2 nmol·kg-1·d-1, ip)，未治疗组注射0.9%生理盐水(1  mL·kg-1·d-1, ip)。动物完成药物注射后，在整体心脏Langendorff灌流条件下行离体电生理研究，分别记录和测量左室前游离壁(LAF)心外膜单相动作电位(MAP)和心室有效不应期(VERP)；行程控增频电刺激以观察动作电位时程(APD)电交替(ALT)；给予Burst快速电刺激进行VA的诱发。用酶解法分离获得LAF处单个心室肌细胞，采用全细胞膜片钳技术记录L型Ca2+通道电流(ICa-L)。结果：与CTL组相比，未治疗组ICa-L峰电流密度、90%单相动作电位时程(MAPD90)、VERP、诱发APD-ALT最大起搏周长(PCLmax)中位数及VA诱发率均显著增大(均P<0.01)；而CST组MAPD90和VERP均增大(P<0.01)，其它指标差异无统计学意义(均P>0.05)；与未治疗组相比，CST组ICa-L峰电流密度、MAPD90、VERP、诱发APD-ALT的PCLmax中位数(80 ms vs 100 ms)及VA诱发率均减小(均P<0.05)，而VERP/MAPD90增大。结论：CST治疗可减少CHF大鼠VA诱发率，其机制可能与CST抑制CHF大鼠ICa-L有关。     

缬草提取物对慢性心力衰竭室性心律失常兔电生理指标的影响

目的:观察缬草提取物(VOL)对慢性心力衰竭(CHF)致室性心律失常兔电生理指标的影响。方法:雄性新西兰大耳白兔30只,随机平分为三组:正常对照组(Control组)、CHF模型组(CHF组)和CHF+VOL组(VOL组)。CHF模型组经耳缘静脉推注异丙肾上腺素(0.3mg/kg/天,连续注射3周)诱导;Control组平行推注等体积生理盐水;VOL组对CHF兔持续静脉滴注浓度为50mg/L的VOL。记录各组在体心脏左心室单相动作电位(MAP)主要参数静息膜电位(RMP)、动作电位幅度(APA)、动作电位最大上升速率(Max_(dv/dt))和动作电位复极化恢复时程(APD_(10-90));观察各组室性心律失常诱发周长(BCL)、诱发率和心律失常持续时间;分离单个心室肌细胞后,全细胞膜片钳技术记录心室肌细胞L-型钙电流(I_(Ca-L))及电流-电压(I-V)曲线。结果:与Control组比较,CHF组RMP、APA、Max_(dv/dt)均明显降低,APD10、APD20、APD50和APD90均显著延长(P均0.01);与CHF组比较,VOL组RMP、APA、Max_(dv/dt)均明显增加,各APD时程均显著缩短(P0.01)。CHF组诱发室性心律失常BCL、心律失常诱发率和持续时间均大于Control组(P0.01);VOL组BCL、心律失常诱发率和持续时间均小于CHF组(P0.01)。当钳制电位为+20mV时,与Control组比较,CHF组心室肌细胞I_(Ca-L)电流密度由(-12.13±0.99pA/pF)下降为(-7.14±0.33pA/pF)(P0.01);VOL组则较CHF组I_(Ca-L)电流密度明显上升(-10.86±0.50pA/pF)(P0.01),VOL组I_(Ca-L)的I-V曲线较CHF组明显下移,接近Control组。结论:VOL能显著降低CHF心室肌电生理易损性和室性心律失常易感性,拮抗CHF室性心律失常;其机制可能与VOL可增加心室肌细胞I_(Ca-L)有关。     

淫羊藿苷对兔充血性心力衰竭引起室性心律失常的影响及其电生理机制

目的:探讨淫羊藿苷（ICA）对家兔充血性心力衰竭（CHF）引起室性心律失常的影响及其电生理机制。方法:实验分为对照组、CHF组和CHF+ICA组（ICA组），采用雄性新西兰大耳白兔。CHF模型制备是经兔耳缘静脉注射异丙肾上腺素（0.3 mg/kg/d，连续注射3周）诱导，然后继续喂养并观察临床指征、M型超声心动图指标中左心室射血分数及短轴缩短率和Ⅱ导心动图的心率、QT间期等主要参数变化以确定CHF模型成功。利用记录在体心室肌单相动作电位和程控电刺激技术以及短阵快速刺激方法观察各组动作电位的最大上升速率（Maxdv/dt）和复极化到20%、50%和90%时程（APD20、APD50、APD90）等主要参数以及基础刺激周长为150 ms时心室有效不应期（ERP150）及其离散度（dERP150）和室性心律失常诱发周期及其诱发率。酶解法分离单个心室肌细胞，全细胞膜片钳技术记录心室肌细胞L-型钙电流（ICa-L）及其电流-电压（I-V）曲线。结果:当入选制造模型的兔出现消瘦、无力、气促和肌肉萎缩等临床症状，心室射血分数和短轴缩短率均明显减小，左心室腔明显扩大，室间隔显著变薄（P均<0.01），心率减慢（P<0.05），PR和QT间期均显著延长（P<0.01），ST段明显上移（P<0.05），提示CHF模型制造成功。与CHF组比较，经ICA治疗的兔心室肌组织的动作电位幅度明显增加，Maxdv/dt加快，APD10、APD20、APD50和APD90均明显缩短（P均<0.01）。另外，ICA组的CHF兔的心室肌组织ERP150及其离散度dERP150以及被诱发室性心律失常的基础刺激周长明显缩短，室性心律失常诱发率显著减少（P<0.01）。最后，经电压钳制，在ICA作用下，CHF心室肌细胞ICa-L明显减小，I-V曲线显著上抬，当钳制电压为+10 mV时，经ICA治疗的CHF兔心室肌细胞ICa-L峰值大小由原CHF组心室肌细胞ICa-L电流密度的（9.98±0.53） pA/pF减小为（6.95±0.15） pA/pF（P<0.01）。结论:ICA能够明显改善家兔CHF引起的心室电重构，降低CHF心脏对室性心律失常的易感性，起到抗CHF引起的室性心律失常作用，其机制可能是ICA能显著抑制CHF心室肌细胞ICa-L，防治CHF心室肌细胞内Ca2+超载和Ca2+振荡。     

参松养心胶囊对糖尿病大鼠心室电生理特性及结构功能变化的影响

 目的：探讨参松养心胶囊（SSYX）对糖尿病（DM）大鼠心室电生理特性与结构功能变化的影响。方法：雄性SD大鼠45只，随机分为对照组（CTL组，n=15）、DM组（n=15）和SSYX组（n=15）。DM组和SSYX组采用一次性腹腔注射链脲佐菌素（60 mg/kg）制备糖尿病模型，CTL组则给予腹腔注射生理盐水（1 mL/kg），72 h后检测血糖评价造模结果，将造模成功的动物纳入本研究。SSYX组连续6周给予SSYX灌胃（1 g·kg-1·d-1）治疗，DM组和CTL组则给予生理盐水灌胃（2 mL·kg-1·d-1）。动物完成药物治疗后，采用超声心动图检测心功能并记录II导联体表心电图；采用放射免疫法检测血浆的内皮素1（ET-1）水平；随后在整体心脏Langendorff灌流条件下行离体电生理研究，分别记录和测量左室前游离壁（LAF）心外膜单相动作电位（MAP）和有效不应期（VERP），同时给予Burst快速电刺激用以进行室性心律失常（VA）的诱发；采用Masson染色对3组动物心肌纤维化程度进行评价。结果：与CTL组相比，DM组心功能下降（P<001），而QT间期、VERP、动作电位时程、VA诱发率、心肌纤维化程度和血浆ET-1水平均增加（均P<001）；与DM组相比，SSYX组的心功能得到改善（均P<001），且 QT间期、VERP、动作电位时程、VA诱发率、心肌纤维化程度和血浆ET-1水平均降低（均P<005）。结论：SSYX具有减轻DM大鼠心室电重构和结构重构及改善心功能的作用。     

右心室快速起搏致心力衰竭犬的心室电生理特性

目的: 研究右心室快速起搏致充血性心力衰竭(CHF)犬心室电生理特性。方法： 16只犬随机分为正常对照组（n=7）和CHF组（n=9），应用右心室快速起搏（240 pulse·min^-1）4-5周制作CHF犬模型，应用心脏电刺激和单相动作电位（MAP）记录技术测定心室生理指标。结果： （1）CHF组心室有效不应期、心室MAP时程、复极后期及传导时间均延长，分别延长26%（P<0.01）、43%（P<0.01）、318%（P<0.05）和19%（P<0.01）；（2）CHF组心室有效不应期与MAP时程的比值减小13%（P<0.05）；（3）CHF组兴奋恢复时间离散性增加185%（P<0.01）；（4）CHF组室颤阈值降低48%（P<0.01）。结论： CHF异常的心室电生理特性可能是导致恶性心律失常及心脏性猝死发生的基础。     

TNF-α对大鼠离体心肌组织块单相动作电位的影响及机制研究

目的:检测TNF-α对离体心肌组织块单相动作电位时程(MAPD)及离子通道电流的影响,初步探讨心梗后TNF-α诱导电生理异质性致室性心律失常发生的可能机制。方法:在离体大鼠心脏灌流的条件下,分离心肌组织块,电生理实验技术记录在不同浓度TNF-α灌流条件下的MAPD。用酶解法分离大鼠的心室肌细胞,应用膜片钳全细胞技术记录不同浓度TNF-α对单个心室肌细胞Ito和IK1的影响。结果:与对照组相比较,离体心肌组织块心内膜和心外膜MAPD浓度依赖性地随着TNF-α浓度的增加而增大(P<0.05);相同浓度TNF-α对心内膜和心外膜MAPD有不同的影响,尤其显著延长了心内膜的MAPD。经依那西普(TNF-α受体螯合剂)预处理后,相同浓度TNF-α对心内膜和心外膜MAPD影响不同导致的差异显著降低(P<0.05)。将TNF-α作用于大鼠心室肌细胞,与对照组相比较,Ito和IK1电流密度随着TNF-α浓度的增加而降低(P<0.05)。结论:TNF-α对心内膜及心外膜单相动作电位的不同影响可能对急性心梗后室性心律失常的形成有诱导或促进作用,其机制可能与TNF-α浓度依赖性抑制Ito和IK1电流,引起动作电位复极化异常从而诱发折返性心律失常有关。     

复方丹参注射液对室性心律失常心内膜单相动作电位的影响

目的观察丹参注射液对室性心律失常时兔心内膜单相动作电位（MAP）变化的影响,初步探讨其抗心肌缺血致心律失常的作用机制。方法20只家兔随机分为丹参组和对照组,丹参组在心肌缺血造模前静脉注射10ml复方丹参注射液（3 g/kg）,对照组注射等容积的生理盐水,每日1次,连续12 d,于第13 d行室性心律失常造模;在造模前后分别检测、记录各项观察指标。结果造模前丹参组平均心率高于对照组,最大除极速度（Vmax）低于对照组（P〈0.05）,MAP振幅（MAPA）、单相动作电位时程（APD90）与对照组无差别。造模后,20只实验兔均出现心律失常,对照组平均心率、MAPA和Vmax降低,APD90增加（P〈0.05）;丹参组平均心率、MAPA降低（P〈0.05）,Vmax与APD90无变化。丹参组在造模后,平均心率高于对照组,APD90低于对照组（P〈0.05）;Vmax与MAPA在造模后的两组无明显差别。结论丹参能提高心内膜心肌缺血耐受的能力,起到了ATP敏感性钾通道开放剂效应。     

慢性心力衰竭兔心室结构重构导致心功能和电生理异常及其意义探讨

目的:探讨慢性心力衰竭(心衰)兔心室结构重构导致心功能和电生理异常及其意义。方法:25只雄性新西兰大耳白兔,其中14只制备慢性心衰模型(心衰组),最终造模成功10只,另11只作为对照组(手术时1只气胸致兔死亡,余10只进入实验)。利用Masson染色技术观察各组心室肌组织间质胶原纤维并计算间质胶原容积系数(CVF),透射电镜观察心室肌细胞超微结构改变。监测各组兔M型超声心动图和Ⅱ导心电图,观察左心室射血分数(LVEF)、主动脉最大流速(Av_(max))、左心室舒张末期内径(LVEDd)和室间隔厚度(IVST)以及心率、PR间期、QT间期和ST段,评价心功能和电生理变化。程控刺激方法观察刺激周长(BCL)为150ms和200ms时心室有效不应期(ERP_(150)和ERP_(200))以及各自有效不应期离散度(dERP_(150)和dERP_(200))。评价Burst-pacing诱发室性心律失常(VA)的BCL和诱发率。结果:与对照组比较,心衰组心室肌组织中胶原纤维明显增多,CVF显著升高(P0.01)。心室肌细胞排列不规则,出现断裂坏死,且超微结构异常改变,心房肌细胞核固缩,线粒体排列杂乱、肿胀或出现空泡,肌小节损伤严重。心衰组LVEF和Av_(max)显著下降(P均0.05),LVEDd明显延长,IVST变薄(P均0.01),且心率明显减慢,PR和QT间期均显著延长(P均0.01),ST段明显下移(P0.05)。与对照组比较,心衰组兔ERP_(150)和ERP_(200)均显著延长, dERP_(150)和dERP_(200)均明显增大,且心衰兔被诱发VA的BCL显著延长,VA诱发率明显加大(P均0.01)。结论:心衰兔心室组织发生明显的病理性改变和超微结构异常的结构重构,造成心室功能下降和电生理紊乱,易于诱发VA。     

儿茶酚抑素对心肌梗死大鼠心室肌细胞钙转运及室性心律失常的影响

目的:探讨儿茶酚抑素(CST)对心肌梗死(MI)大鼠心室肌细胞钙转运及室性心律失常(VA)的影响。方法:雄性SD大鼠85只,随机分为假手术(sham)组(n=20)和手术组(n=65)。手术组动物结扎左冠状动脉前降支制备大鼠MI模型,假手术组只剪开心包并不结扎冠状动脉。将术后存活1周的手术组大鼠随机分为梗死对照组(MI组)和CST干预组(CST组)。CST组给予CST(30 mg·kg~(-1)·d~(-1))连续4周腹腔注射,MI组和假手术组则注射等量生理盐水。急性分离大鼠心室细胞,钙荧光染料Fura-2 AM孵育后行心肌细胞钙成像实验。在Langendorff灌流条件下行离体电生理研究,评价各组动作电位时程(APD)电交替及VA易感性。Western blot法检测心室钙/钙调素依赖性蛋白激酶II(CaMKII)、磷酸化CaMKII(p-CaMKII)、ryanodine受体2(RyR2)及磷酸化RyR2(p-RyR2)的蛋白水平。结果:与sham组相比,MI组心室p-RyR2和p-CaMKII蛋白水平、心室细胞舒张期Ca~(2+)水平及VA诱发率均显著升高,而心室细胞Ca~(2+)瞬变(CaT)幅度、CaT交替诱发阈值及APD电交替诱发阈值均显著降低(P0.01);与MI组相比,CST组心室p-RyR2和p-CaMKII蛋白水平、心室细胞舒张期Ca~(2+)水平及VA诱发率均显著降低,而心室细胞CaT幅度、CaT交替诱发阈值及APD电交替诱发阈值均显著增加(P0.01)。心室RyR2及CaMKII的表达量在3组间差异无统计学显著性(P0.05)。结论:CST可降低MI大鼠VA易感性,其机制可能与CST修复心室细胞Ca~(2+)转运有关。     

心力衰竭犬跨室壁心肌复极时间和不应期离散度的致心律失常机制研究

目的：从复极和不应期两个角度,观察不同部位起搏对心力衰竭犬三层心肌跨室壁复极和不应期离散度的影响及其可能的致心律失常机制。方法：正常犬8只和心力衰竭模型犬5只,模拟临床上充血性心力衰竭患者接受心脏再同步治疗的情况,分别从右心室心内膜、左心室心外膜和双心室发放刺激,在体记录和比较犬三层心肌的单相动作电位时程、不应期及其跨室壁离散度。在心力衰竭犬组,给予维拉帕米进行干预并重复上述实验。结果：心力衰竭犬三层心肌的动作电位时程与不应期均有延长,中层心肌动作电位时程延长最明显 [(279.30±54.81) ms vs (270.03±57.58) ms,P<0.01],跨室壁复极离散显著增大 [(29.80±25.67) ms vs (20.60±12.65) ms,P<0.01],不应期离散有所减小 [(29.21±15.83) ms vs (31.25±20.83) ms,P>0.05];左心室心外膜和双心室刺激增加跨室壁复极离散度,但对跨室壁不应期离散度无明显影响;维拉帕米能在一定程度上延长中层和心外膜下心肌的动作电位时程与不应期,减小跨室壁复极和不应期离散 [心力衰竭犬给予维拉帕米后 (24.50±15.18) ms vs 正常犬 (31.25±20.83) ms,P<0.05]。结论：心力衰竭犬跨室壁复极离散增大、不应期离散减小;维拉帕米减小心力衰竭犬跨室壁复极与不应期离散;左心室心外膜参与的起搏方式对心肌不应期无明显影响,但增大跨室壁复极离散,且这一效应不能被维拉帕米矫正。     

瑞芬太尼对兔心肌动作电位及跨室壁复极离散度的影响

目的:观察瑞芬太尼对兔心肌动作电位及跨室壁复极离散度的影响。方法:成年家兔18只,体重2.0~2.5 kg,制备Langendorff离体心脏灌注模型,K-H液平衡灌注15 min后随机分为3组(n=6):正常对照组(C组)继续灌注37℃K-H液60 min;瑞芬太尼组(R组)灌注含12μg/L瑞芬太尼的K-H液60 min;瑞芬太尼+氨茶碱组(RA组)灌注含12μg/L瑞芬太尼+30 mg/L氨茶碱的K-H液60 min。记录平衡灌注15 min(T0)、继续灌注15 min(T1)、30 min(T2)和60 min(T3)时心率(HR)和左心室前壁3层心肌单相动作电位(MAP),计算单相动作电位复极90%的时程(MAPD90)和跨室壁复极离散度(TDR)。记录早期后除极、延迟后除极及心律失常的发生情况。结果:与T0比较,R组T1~T3时HR减慢,MAPD90延长,TDR增大(P0.05)。与C组和RA组比较,R组HR减慢时,MAPD90延长,TDR增大(P0.05)。结论:瑞芬太尼减慢HR时,MAPD90延长,TDR增大,折返激动易于发生;氨茶碱增快HR,缩短MAPD90,从而使TDR减小。     

Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias

Ischemic preconditioning has been acknowledged as a powerful method of decreasing ischemic injury. However, the antiarrhythmic mechanism of ischemic preconditioning during ischemia is unclear. We studied the effects of ischemic preconditioning on arrhythmias and cardiac electrophysiology during ischemia in Langendorff rat hearts (n = 44). In the non-preconditioned group (PC(-); n = 24), the hearts underwent 5-min zero-flow global ischemia without any prior ischemic preconditioning. In the preconditioned group (PC(+); n = 20), the hearts were preconditioned by three cycles of 3-min zero-flow global ischemia and 5-min reperfusion before undergoing 5-min global ischemia. Ischemic preconditioning reduced the incidence of ischemia-induced arrhythmias (PC(-); 38.9%, PC(+): 8.3%, p < 0.05), shortened monophasic action potential duration (MAPD, P < 0.05), attenuated conduction delay (conduction time; PC(-): 234.2%, PC(+): 173.4%, P < 0.05) and increased the ventricular fibrillation threshold. Although the shortening of MAPD in PC(-) hearts was not influenced by the presence or absence of arrhythmias, conduction time prolongation at 3-min was more obvious in PC(-) hearts with arrhythmia than in PC(-) hearts without arrhythmia (PC(-) with arrhythmia: 220.2%, PC(-) without arrhythmia: 190.7%, P < 0.05). We concluded that ischemic preconditioning could protect the rat hearts from ischemia-induced arrhythmias and postulated that attenuation of conduction delay during ischemia might be an important factor in the antiarrhythmic action of ischemic preconditioning.     

Electrophysiological effect of rotigaptide in rabbits with heart failure

Introduction

Rotigaptide is a new anti-arrhythmic peptide, which has recently been found to increase junctional conductance and prevent ischemia-induced ventricular tachycardia. In this study, we attempted to investigate the effects and mechanisms of rotigaptide on the vulnerability to ventricular arrhythmias in rabbits with heart failure (HF).

Material and methods

Chronic volume-pressure overload was used to induce HF. After rotigaptide infusion, an electrophysiological study was performed to record monophasic action potential (MAP), determine the effective refractory period (ERP) and ventricular fibrillation threshold (VFT), and assess the susceptibility to ventricular arrhythmia. Finally, real-time PCR was used to detect the changes of connexin 43 (Cx43) mRNA expression.

Results

HF rabbits exhibited significant down-regulation of Cx43 mRNA, increase of effective refractory period (ERP) and decrease of VFT (p < 0.05, respectively). These changes resulted in an increase of vulnerability to ventricular tachyarrhythmias (VT/VF). Rotigaptide administration shortened ERP (113.3 ±8.6 ms vs. 131.7 ±12.5 ms, p < 0.05), restored VFT (15.0 ±2.0 V vs. 6.3 ±1.4 V, p < 0.05), and decreased the vulnerability to VT/VF. However, short-term rotigaptide treatment had no significant effect on MAP duration (MAP duration at 90% repolarization: 169.3 ±6.0 ms vs. 172.7 ±6.2 ms, p > 0.05) or connexin 43 mRNA expression (p > 0.05).

Conclusions

Rotigaptide decreases the ERP, elevates VFT, and reduces the vulnerability to ventricular arrhythmias without changing Cx43 expression in rabbits with HF. It may be a promising antiarrhythmic drug for preventing ventricular arrhythmia in HF.     

溶血磷脂酰胆硷在离体绵羊心肌缺血引起的心律失常中的作用

用台氏液加溶血磷脂酰胆硷灌流离体绵羊心室小梁肌，其０期去极化最大速率、静息电位（ＲＰ）、动作电位幅值（ＡＰＡ）、动作电位复极达ＡＰＡ５０％和９０％的时程ＡＰＤ５０、ＡＰＤ９０分别下降３９．８％、１０．４％、１４．５％、２１．３％和１４８％；用“模拟缺血溶液”加ＬＰＣ，其Ｖｍａｘ、Ｘｐ、ＡＰＡ、ＡＰＤ５０、ＡＰＤ９０分别下降７８％、２２．７％、２６％、３５．４％和２１％，对“模拟缺血溶液”中各种成分     

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.     

Vulnerability to ventricular arrhythmias [corrected] and heterogeneity of action potential duration in normal rats

In normal rats, we analysed the arrhythmogenic role of intrinsic action potential duration (APD) heterogeneity. In each animal, ventricular arrhythmic events (VAEs) occurring spontaneously and during the exposure to an acute social challenge were telemetrically recorded. Action potentials were recorded from isolated left ventricular myocytes, at a pacing rate of 5 Hz (patch clamp: current-clamp mode). APDs were measured at -20 mV, -30 mV, -40 mV, -50 mV and -60 mV. The difference between the shortest and the longest APD was also computed, as an index of individual APD heterogeneity. Animals predisposed to stress-induced arrhythmias showed higher values of APD and APD heterogeneity as compared with the remaining rats. We concluded that, in the normal heart, a large intrinsic APD heterogeneity resulting from specific electrophysiological properties of ventricular myocytes is not in itself arrhythmogenic, but can predispose towards arrhythmia development under certain conditions, such as autonomic activation.