充血性心力衰竭跨室壁复极不均一性的改变

目的研究充血性心力衰竭模型左心室三层心肌之间单相动作电位的改变。以探讨充血性心力衰竭易发心室颤动的基础电生理机制。方法用阿霉素制作充血性心力衰竭家兔模型，测定其室颤阈值（VFT）以及心外膜、中层心肌和心内膜心肌细胞的单相动作电位复极90％时程（APD90）、跨室壁复极离散度（TDR）。结果充血性心力衰竭VFT明显降低，三层心肌细胞APD90均明显延长，但中层心肌细胞较心外膜、心内膜下心肌细胞延长更为显著；充血性心力衰竭跨室壁TDR增加。结论中层心肌细胞APD90明显延长、跨室壁TDR增加可能是充血性心力衰竭容易发生心室颤动的重要原因。     

扩张型心肌病家兔左室壁复极异质性的改变及意义

目的：观察离体心脏左心室三层心肌的单相动作电位的改变，以探讨扩张型心肌病易发心室颤动与三层心肌跨室壁复极不均一性的关系。方法：用阿霉素制作扩张型心肌病家兔模型，测定其室颤阈值（VFT）以及心外膜、中层心肌和心内膜心肌细胞的单相动作电位复极90％时程（APD90）、跨室壁复极离散度（TDR）。结果：扩张型心肌病VFT明显降低（P＜0．001），三层心肌细胞APD90均明显延长（P＜0．001），中层心肌细胞较心外膜、心内膜下心肌细胞延长更为显著（P＜0．05）；扩张型心肌病跨室壁复极离散度增加（P＜0．01）。结论：中层心肌细胞APD90明显延长、跨室壁复极离散度增加、三层心肌复极不均一性增加可能是扩张型心肌病容易发生心室颤动的重要原因。     

低钾对扩张型心肌病跨室壁复极不均一性的影响

目的　研究低钾是否为扩张型心肌病 (DCM )发生室性心律失常的重要促发因素及其电生理机制。方法　将家兔随机分成DCM实验组及正常对照组 ,建立DCM家兔模型并进行离体心脏灌流 ,观察低钾时两组之间 3层心肌APD及跨室壁复极离散度 (TDR)的改变。结果　低K+ 灌流时DCM实验组和正常对照组中层心肌细胞单相动作电位复极 90 %时程 (APD90 )、TDR均长于正常K+ 灌流 (P <0 0 0 1) ,但以DCM实验组延长更为明显 (P <0 0 0 1)。结论　低K+ 延长中层心肌细胞APD ,增加跨室壁复极不均一性 ,可能是DCM易发室性心律失常的重要促发因素。     

Ang Ⅱ对左心室心肌跨室壁复极不均一性的影响

目的 观察AngⅡ灌流对家兔左心室心肌跨室壁复极不均一性及Cx43蛋白分布异质性的影响,探讨AngⅡ在恶性室性心律失常(MVA)发生中的作用.方法 将20只家兔随机分成正常对照组和AngⅡ灌流组,正常对照组离体心脏给予单纯改良台氏液灌流,AngⅡ灌流组则给予含1μmol AngⅡ的台氏液灌流,分别检测两组家兔的室颤阈值(VFT)及心外膜下、中层心肌和心内膜下心肌细胞的单相动作电位复极90％时程(APD90)、跨室壁复极离散度(TDR)以及三层心肌Cx43蛋白表达的差异.结果 ①正常对照组和AngⅡ灌流组的VFT分别为(13.40±2.950)V和(8.30±1.77)V,两组对比差异有统计学意义(P＜0.001).②与正常对照组比较,AngⅡ灌流组三层心肌的APD90均明显延长(P＜0.05).AngⅡ灌流组和正常对照组的△APD9分别为(34.70±9.68)ms和(23.70±5.68)ms,TDR分别为(49.30±13.52)ms和(36.10±12.44)ms,AngⅡ灌流组均明显大于正常对照组(P＜0.05),说明AngⅡ灌流组中层心肌APD90的延长较心外膜下和心内膜下心肌更为明显.③与正常对照组比较,AngⅡ灌流组三层心肌的Cx43蛋白表达均有明显下降(P＜0.05),但以中层心肌的下降最为显著.结论 AngⅡ灌流改变了正常家兔左心室心肌的跨室壁Cx43表达异质性,使左心室心肌跨室壁复极不均一性增大,VFT下降,更加容易诱发MVA.     

稳心颗粒对急性心肌缺血的左心室电生理特性的影响

目的研究步长稳心颗粒对家兔缺血心肌左心室内、外膜电生理特性的影响,探讨该药抗心律ar-rhythmia失常的机制。方法在急性缺血条件下,应用浮置玻璃微电极microelectrode记录技术,记录用药前后家兔左室游离壁free wall内、外膜心肌细胞跨膜动作电位transmembrane action potential(TAP),观察动作电位时程ac-tion potential duration(APD)、心室跨壁tanswall复极离散度repolarization dispersion(TDR)的变化。结果①左心室楔形cuneiform组织块停止灌注perfusion后,用药组内、外膜心肌细胞的动作电位时程(APD)缩短,停止灌注时间5 min,10 min,15 min时,内、外膜心肌细胞的动作电位时程逐渐缩短,外膜缩短程度大于内膜(P<0.01)。②急性缺血情况下,用药组的心室跨壁复极离散度(TDR)小于对照组,当停止灌注5 min时,对照组的TDR为(37±12)ms,步长用药组为(30±10)ms(P<0.05)。结论步长稳心颗粒具有抗心肌缺血作用,使缺血情况下左室TDR缩短。     

普伐他汀对兔急性心肌缺血室性心律失常的影响

目的观察普伐他汀对兔急性心肌缺血室性心律失常的影响并探讨其作用机制。方法将36只家兔随机分为对照组、缺血再灌组和普伐他汀组，每组各12只。制备冠脉灌流的兔左心室楔形心肌块的灌注模型，采用浮置玻璃微电极法同步记录楔形心肌块心内膜、心外膜心肌细胞跨膜动作电位和跨室壁心电图。观察各组缺血30 min和再灌注15 min时的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），同时记录各组缺血和再灌注时室性心律失常的诱发率。结果①缺血状态下缺血再灌组较对照组TDR和心律失常的诱发率显著增加（均P〈0.01），普伐他汀组和缺血再灌组与对照组相比，TDR和心律失常的诱发率显著减少（均P〈0.05），对照组、缺血再灌组和普伐他汀组室性心律失常的诱发率分别为0/12、9/12、2/12。②再灌注状态下缺血再灌组和普伐他汀组TDR和室性心律失常的发生率差异均无显著性意义（均P〉0.05）。结论普伐他汀可显著降低兔急性缺血心肌跨室壁复极离散度和室性心律失常发生率，并能够改善缺血心肌的各项异常电生理指标。     

药物致尖端扭转型室性心动过速的发生机制

目的探讨药物致尖端扭转型室性心动过速（Tdp）的发生机制。方法建立冠状动脉灌注的犬左室心肌楔形组织块模型,
同步记录左心室内膜、中层、外膜心肌细胞的动作电位及跨壁心电图,观察不同浓度D-Sotalol对动作电位时间（APD）、QT间期、
跨壁复极离散度（TDR）、早期后除极（EAD）及Tdp发生的影响。结果浓度为0~100 μmol/L的D-Sotalol呈剂量依赖性地延长
各层细胞APD,尤以中层细胞最为显著（P<0.05）,因而增加TDR;D-Sotalol在中层细胞可诱发EAD,触发室性早博并形成跨壁
折返导致Tdp。结论D-Sotalol在中层细胞诱发EAD、R on T室性早博是其致Tdp的始动因子,在TDR增加的基础上形成跨室
壁折返是Tdp得以维持的关键。
     

药物致尖端扭转型室性心动过速的发生机制

目的探讨药物致尖端扭转型室性心动过速(Tdp)的发生机制。方法建立冠状动脉灌注的犬左室心肌楔形组织块模型,同步记录左心室内膜、中层、外膜心肌细胞的动作电位及跨壁心电图,观察不同浓度D-Sotalol对动作电位时间(APD)、QT间期、跨壁复极离散度(TDR)、早期后除极(EAD)及Tdp发生的影响。结果浓度为0～100μmol/L的D-Sotalol呈剂量依赖性地延长各层细胞APD,尤以中层细胞最为显著(P<0.05),因而增加TDR;D-Sotalol在中层细胞可诱发EAD,触发室性早博并形成跨壁折返导致Tdp。结论 D-Sotalol在中层细胞诱发EAD、R on T室性早博是其致Tdp的始动因子,在TDR增加的基础上形成跨室壁折返是Tdp得以维持的关键。     

灯盏花素对家兔肥厚心肌室性心律失常的影响

目的观察口服灯盏花素对家兔肥厚心肌室性心律失常的影响,探讨灯盏花素抗心律失常的作用机制。方法 30只家兔随机分为假手术组、心肌肥厚组和灯盏花素组,每组10只。假手术组开腹但不行腹主动脉缩窄术;心肌肥厚组和灯盏花素组采用腹主动脉缩窄术制备家兔心肌肥厚模型;灯盏花素组自手术后第2天开始喂服灯盏花素,每只每日1片,喂养8周。制备兔左心室楔形心肌块,利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;测心脏质量(HW)、体质量(BW)和左心室游离壁厚度(LVT)。观察各组QT间期和内、外膜心肌细胞跨膜动作电位以及跨室壁复极离散度(TDR),程序电刺激诱发室性心律失常,记录跨膜动作电位复极90%的时程(APD90),早期后除极(EAD)和尖端扭转性室性心动过速(Tdp)的发生率。结果心肌肥厚组与灯盏花素组HW、HW/BW及LVT值与假手术组相比均明显升高(P<0.05);灯盏花素组HW、HW/BW及LVT值与心肌肥厚组相比均明显减小(P<0.05)。心肌肥厚组与灯盏花素组QT间期及内、外膜心肌APD90较假手术组明显延长(P<0.05);灯盏花素组QT间期及内、外膜心肌APD90与心肌肥厚组相比明显缩短(P<0.05)。假手术组、心肌肥厚组和灯盏花素组TDR分别为(55±17)、(99±12)和(68±11)ms,3组间比较差别有统计学意义(P<0.05)。灯盏花素组EAD和Tdp的发生率明显低于心肌肥厚组(P<0.05)。结论肥厚心肌TDR增大,心律失常的发生率显著升高。灯盏花素可减少TDR,明显降低EAD和Tdp的发生率。     

杭白菊乙酸乙酯提取物对大鼠实验性心律失常的影响及其机制

目的：研究杭白菊乙酸乙酯提取物（CME）对大鼠实验性心律失常、心肌易损性与动作电位的影响及其机制。方法：采用乌头碱诱发的整体大鼠心律失常模型研究cME对大鼠实验性心律失常的影响。采用Langendorff离体心脏灌流方法,结扎冠状动脉左前降支30min后复灌复制局部缺血／复灌模型,测定心肌缺血复灌前后的心室电生理学参数：舒张期兴奋阈（DET）、有效不应期（ERP）、室颤阈（VFT）。采用常规微电极技术记录大鼠右心室乳头肌动作电位,观测静息电位（RP）、动作电位幅度（APA）、有效不应期（ERP）、动作电位的时程（APD90）、动作电位0期最大除极速率（Vmax）。结果：与对照组相比,CME明显降低室性心动过速发生次数,缩短其持续时间,延迟室性早搏、室性心动过速出现时间,心律失常评分显著降低。与对照组相比,CME明显延长离体大鼠心脏的ERP,并对缺血／复灌所致的ERP缩短和VFT降低有明显的减弱作用。与对照组相比,CME明显延长大鼠右室乳头肌动作电位APD50和APD90,降低动作电位Vmax,对动作电位的其他参数影响不显著。结论：CME具有降低大鼠心室易颤性、抗心律失常的作用,其机制可能涉及延长心肌动作电位时程及有效不应期,提高大鼠心脏电生理稳定性。     

正常家兔左心室三层心肌Cx43表达的异质性研究

目的 观察正常家兔三层心肌间跨室壁缝隙连接蛋白43 (Cx43)分布的差异,探讨恶性室性心律失常(MVA)的发生机制.方法 检测并对比正常家兔左心室三层心肌间的单相动作电位复极90%时程(APD90)以及Cx43蛋白(Cx43-pro)和mRNA(Cx43-Cq)的表达差异.结果 (1)正常家兔三层心肌间APD90存在差别,中层心肌(233.80±19.37)组织APD90均长于心内膜(201.20±18.72)和心外膜下(202.70±19.91)心肌组织(P<0.05),说明家兔三层心肌间存在跨室壁复极的离散;(2)正常家兔三层心肌间的Cx43-pro [(0.58±0.08) vs (0.47±0.04) vs (0.57±0.07)]与Cx43-Cq [(24.61±2.82) vs (22.18±2.62) vs (24.43±3.31)]差异均有统计学意义(P<0.05),中层心肌较心内膜与心外膜下心肌组织表达减少,表明家兔三层心肌间存在跨室壁Cx43表达的异质性.结论 正常家兔中层心肌与心内外膜下心肌间存在Cx43蛋白表达不均一,这是左心室存在心肌横断面上复极离散的蛋白基础.     

胺碘酮对左室肥厚家兔跨室壁Cx43异质性的影响

目的：观察胺碘酮片剂对左室肥厚(LVH)家兔三层心肌间Cx43表达的差异,探讨LVH恶性室性心律失常(MVA)的机制及处理措施。方法将20只家兔按随机数字法分成胺碘酮治疗组和LVH对照组,每组各10只。两组家兔均采用传统的腹主动脉缩窄术后继续喂养8周以制备LVH模型。治疗组手术后给予经口喂服盐酸胺碘酮片,每日50 mg/kg,连续4周,然后继续喂养4周并进行实验;对照组喂养生理盐水8周后进行实验。分别检测两组家兔心外膜下、中层心肌和心内膜下心肌细胞的单相动作电位复极90%时程(APD90)、跨室壁复极离散度(TDR)以及左心室三层心肌Cx43蛋白表达的差异。结果(1)治疗组家兔心内、外膜下、中层心肌的APD90分别为(275.30±11.42) ms、(251.50±10.98) ms和(295.40±12.41) ms,均较LVH对照组的(236.30±16.51) ms、(217.69±14.25) ms和(265.12±20.01) ms显著延长,差异具有显著统计学意义(P<0.01),但是治疗组的TDR为(38.96±10.91),明显小于对照组的(48.56±11.23),差异有统计学意义(P<0.05)。(2)治疗组家兔三层心肌的Cx43蛋白表达分别为(0.60±0.07)、(0.48±0.05)和(0.57±0.06),均较对照组的(0.53±0.04)、(0.31±0.06)和(0.48±0.04)明显提高(P<0.05),但以中层心肌的增加更为明显,从而缩小了三层心肌间Cx43蛋白表达的差异,△Cx43减少[(0.14±0.06) vs (0.23±0.08),P<0.01]。结论胺碘酮能改善左室肥厚的跨室壁Cx43表达异质性,缩小左心室心肌跨室壁复极不均一性,这可能是其减少MVA发作的生理机制。     

Effect of Lidocaine and Amiodarone on Transmural Heterogeneityricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.     

Carvedilol suppresses ventricular arrhythmia in a pressure over-load rabbit model through relieving transmural dispersion of repolarization with long-term administration

ObjectiveTo investigate the effects of carvedilol (CVD) on transmural dispersion of repolarization (TDR) and arrhythmia in pressure over-load rabbits.MethodsLeft ventricular hypertrophied (LVH) rabbit models were established by pressure over-load; All animal models were assigned into CVD group or LVH group randomly. The action potentials of endocardium, epicardium and transmural ECG of arterially perfused left ventricular preparations were recorded concurrently. Action potential duration (APD), TDR, ventricular arrhythmia and ultrasonic parameters, ratio of LVM to body weight (LVMI) were compared correspondingly. The stable plasma concentration of carvedilol in CVD group was detected by HPLC. APD, TDR and arrhythmia of LVH models were compared just pre- or post-perfusion with stable concentration of CVD.ResultsIn Contrast with values in LVH group, LVEF of CVD group were significantly elevated while the LVMI was remarkably reduced, TDRs were significantly shortened, and ratio of ventricular arrhythmia was lowered remarkably. No significant difference of APD, TDR and ratio of arrhythmia was found preor post-perfusion at stable plasma concentration of CVD.ConclusionCVD can ameliorate the structure and function of pressure over-load ventricles; CVD contributes to the improvement of ventricular arrhythmia associated with its long-term effect on APD, TDR shortening, whereas has nothing to do with its transient function on ionic channel blockade.     

Effect of Lidocaine and Amiodarone on Transmural Heterogeneity of Ventricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

Someresultsofmeta analysesofrandomizedcontroltrialsonmyocardialinfarctionfoundthatlidocaineandamiodaronecanbeusedforthetreat mentofventriculartachyarrhythmias,butlido cainedonotreducemortalityinpatientswithven triculararrhythmiasaftermyocardialinfarctionwhileamiodaronecan[1,2].Themechanismisnotfullyunderstood.Inrecentyears,discoveryoftheMcells,andthreelayersmyocardiumtheorybeendrawed,thatmostelectrophysiologicalphenomenahadgotnewexplains[3,4].Thisexperimentthemonophasicactionpotentials(MAPs)…     

雷米普利对兔心肌梗死后心室肌电生理的影响

目的:探讨血管紧张素转化酶抑制剂雷米普利对兔心肌梗死后室性心律失常发生的影响及其可能机制.方法:24只家兔随机分为假手术组(SHAM)、心肌梗死组(MI)和雷米普利组(RAM).3组均在无菌条件下开胸,其中心肌梗死组和雷米普利组分别结扎左冠状动脉前降支.雷米普利组术后第2天给予雷米普利[1 mg/(kg·d)],3组共...     

Effects of Potassium Aspartate and Magnesium on Ventricular Arrhythmia in Ischemia-reperfusion Rabbit Heart

The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischemia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.