Changes of Monophasic Action Potential Duration and Effective Refractory Period of Three Layers Myocardium of Canine during Acute Ischemia in Vivo

Summary： The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of canine in vivo was investigated. Twelve canines were divided into two groups randomly： acute ischemia （AI） group and sham operation （SO） group. By using the monophasic action potential （MAP） technique, MAP and effective refractory period （ERP） of the three layers myocardium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization （TDR） and transmural dispersion of ERP （TDE） were analyzed. The results showed that in the AI group, MAP duration （MAPD） was shortened from 201.67±21.42 ms to 169.50±13.81 ms （P〈0.05）, but ERP prolonged to varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis.

Effect of dexmedetomidine on monophasic action potential amplitude in myocardial ischemia-reperfusion and its correlation with myocardial injury

Objective: To study the effect of dexmedetomidine on monophasic action potential amplitude (MAPA) in myocardial ischemia-reperfusion and its correlation with myocardial injury. Methods: SD rats were selected as the experimental animals and randomly divided into control group, ischemia reperfusion group (I/R group) and dexmedetomidine group (Dex group);I/R group and Dex group were made into myocardial ischemia-reperfusion injury models, and Dex group were given exmedetomidine intervention;the MAPA of myocardial tunica intima layer, tunica media layer and tunica externa layer were measured in Langendorff perfusion system;myocardial tissue was collected to determine the contents of oxidative stress molecules and the expression of apoptosis genes. Results: The MAPA levels of myocardial tunica intima layer, tunica media layer and tunica externa layer as well as Klotho and SOD contents in myocardial tissue of I/R group were significantly lower than those of control group whereas CaMKII, NOX2, NOX4 and MDA contents as well as CaSR, USP14, JNK, Bax, Fas and Caspase-3 mRNA expression in myocardial tissue were significantly higher than those of control group;the MAPA levels of myocardial tunica intima layer, tunica media layer and tunica externa layer as well as Klotho and SOD contents in myocardial tissue of Dex group were significantly higher than those of I/R group whereas CaMKII, NOX2, NOX4 and MDA contents as well as CaSR, USP14, JNK, Bax, Fas and Caspase-3 mRNA expression in myocardial tissue were significantly lower than those of I/R group;Pearson test showed that the MAPA levels of myocardial tunica intima layer, tunica media layer and tunica externa layer were negatively correlated with CaMKII, NOX2, NOX4 and MDA contents as well as CaSR, USP14, JNK, Bax, Fas and Caspase-3 mRNA expression in myocardial tissue, and positively correlated with Klotho and SOD contents. Conclusion: Dexmedetomidine can increase the MAPA in myocardial ischemia-reperfusion process, and is closely related to the inhibition of oxidative stress response and apoptosis.

Correlation between myocardial ischemia-reperfusion-induced monophasic action potential amplitude change and myocardial damage

Objective:To study the correlation between myocardial ischemia-reperfusion-induced monophasic action potential amplitude (MAPA) change and myocardial damage.Methods:New Zealand rabbits were selected as experimental animals and randomly divided into control group and ischemia-reperfusion group (I/R group), myocardial ischemia-reperfusion injury models were established, then the heart was separated and the MAPA of myocardial intima layer, media layer and outer layer were determined in Langendorff perfusion system;serum samples and myocardial tissue were collected to determine the contents of myocardial injury molecules.Results: MAPA levels of myocardial intima layer, media layer and outer layer of I/R group were significantly lower than those of control group;CK-MB, cTnI, cTnT and MDA contents in serum as well as Bax, Caspase-3 and Caspase-9 mRNA expression in myocardial tissue of I/R group were significantly higher than those of control group and negatively correlated with MAPA levels of myocardial intima layer, media layer and outer layer while SOD, GSH-Px and HO-1 contents in serum as well as Bcl-2 and Bcl-xL mRNA expression in myocardial tissue were significantly lower than those of control group and positively correlated with MAPA levels of myocardial intima layer, media layer and outer layer.Conclusion:Myocardial ischemia - reperfusion can induce the decrease of MAPA and is closely related to myocardial oxidative stress injury and apoptosis.

Construction of Energy-Optimal Smooth Monophasic Defibrillation Pulse Waveforms Using Cardiomyocyte Membrane Model

The goal is to help create smooth energy-optimal monophasic pulse waveforms for defibrillation using the Luo-Rudy cardiomyocyte membrane computer model. The waveforms were described with the help of the piecewise linear function. Each line segment provides a transition from one present level of the transmembrane potential to the next with a minimal energy value. The duration of the last segment was defined as a minimum duration at which an action potential occurs. Monophasic waveforms of segments 3, 10 and 29 were built using different increments of the transmembrane potential. The pulse energy efficiency was evaluated according to their threshold energy ratios in mA2·ms/cm4. There was virtually no difference between the threshold energy ratios of the three waveforms constructed and those of the previously studied energy-optimal half- sine waveform: 241 - 242 and 243 mA2·ms/cm4. The pulse waveform constructed is characterized by a low rise and fall as the duration of the rise is ~1.5 times longer than that of the fall. Conclusion: Energy-optimal smooth monophasic pulse waveforms have the same threshold energy ratio as the optimal half-sine one which was studied before. The latter is equivalent to the first phase of biphasic quasisinusoidal Gurvich-Venin pulse which has been used in Russia since 1972. Thus, the use of the Luo-Rudy cardiomyocyte membrane model appears to offer no possibilities for a substantial increase in the energy efficiency (threshold energy ratio reduction) of the classical monophasic defibrillation pulse waveforms.

Variability in local action potential durations, dispersion of repolarization and wavelength restitution in aged wild-type and Scn5a^＋/- mouse hearts modeling human Brugada syndrome

Brugada syndrome is a primary arrhythmia syndrome characterized by loss-of-function mutations in the SCN5A gene, which encodes for the cardiac Na^＋ channel. In affected individuals, the risk of developing malignant ventricular arrhythmias and sudden cardiac death are increased.

阿魏酸钠抗肾上腺素实验性心律失常作用

目的 :探讨阿魏酸钠在整体水平下的抗肾上腺素心律失常作用及可能机制。方法 :2 4只家兔随机分为对照组、阿魏酸钠组及胺碘酮组 ,各组同步记录体表心电图 (ECG)及右室心内膜单相动作电位 (MAP) ,比较各组按 75 μg·kg-1静脉注射 0 .1%肾上腺素前后ECG及相应MAP变化。结果 :快速静脉注射肾上腺素可引起动作电位时程 (MAPD)缩短 ,并可由自律性增高致室性心律失常。阿魏酸钠作用与胺碘酮相似 ,二者均可拮抗肾上腺素所致MAPD缩短 ,降低室性心律失常发生率 ,延长潜伏期 ,缩短持续时间。且心电图ST段改变的发生率及持续时间亦缩短。结论 :阿魏酸钠可能是一种复合阻滞β受体的钾通道阻滞剂。

单相动作电位同步记录电极的建立和应用

目的 设计跨心室壁三层单相动作电位(MAP)同步记录电极,为跨心室壁复极异质性的在体研究提供有效途径。方法 以改造的 12 号不锈钢针头为外鞘,按先后顺序将彼此绝缘的外、中、内膜电极依次与外鞘组装,经过绝缘性、电导通性检测后,分别在体记录了兔、犬跨左心室壁内、中、外膜心肌的单相动作电位和心电图。结果 ①兔左心室前壁内、中、外三层单相动作电位形态各不相同,中、外膜层 MAP复极起始部分具有典型的“峰和圆顶”特征,内膜层MAP复极过程中不存在明显切迹;在心率为272 次/min时,兔左心室内、中、外层心肌动作电位时程分别为 140、140、130 ms;动作电位幅度分别为17.5、19.31、11.51 mV。②犬中、外膜层心肌复极起始部分具有“峰和圆顶”特征,中膜层心肌1期切迹不如外膜层典型,内膜层心肌复极1期仅有小的切迹;心率为 139 次/min时,犬内、中、外层心肌动作电位时程分别为230、250、200 ms;动作电位幅度分别为46.33、66.41、43.30 mV。结论 自制单相动作电位能清晰、有效的记录在体动物跨心室壁各层的动作电位,可用于跨心室壁复极异质性的在体实验研究。

不同血钾水平时索他洛尔对在体跨室壁心肌复极不均一性的影响

为了观察正常血钾和低血钾时索他洛尔对在体跨室壁心肌复极不均一性的影响 ,探讨索他洛尔致室性心律失常的机制。 2 4只兔随机分为两组 ,正常血钾组 (12只 )和低血钾组 (12只 ) ,分别静注索他洛尔 1.0 m g/ kg,3.0 mg/kg;同步记录兔左室心外膜心肌 (Epi)、中层心肌 (Mid)和心内膜心肌 (Endo)的单相动作电位 (MAP) ,研究发现低钾时与血钾正常时相比 ,索他洛尔增加跨室壁心肌复极离散度 (TDR)的作用更明显 ;更易引起 Mid发生早期后除极 (EAD) ;低血钾组尖端扭转性室速 (Td P)

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（ P＜0.05）。与C组和RA组比较，R组HR减慢时，MAPD90延长，TDR增大（P＜0.05）。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。

阿魏酸钠对家兔心室肌单相动作电位的影响

目的 探讨阿魏酸钠对心肌细胞单相动作电位的影响。方法 健康家兔 2 0只 ,随机平均分为两组 :对照组 (苄基四氢巴马汀组 )和实验组。按传统心内膜MAP记录方法经右颈外静脉插入四极接触电极导管至家兔右心室内膜记录MAP信号并同时记录Ⅱ导联心电图。对照组经耳缘静脉给予苄基四氢巴马汀 ( 5mg·kg-1) ,实验组给予阿魏酸钠( 0 6g·kg-1) ,给药前、后观察MAPA、MAPD5 0、MAPD90及ERP。结果 对照组用药前MAPA及MAPD2 0分别为( 2 7 0 1± 0 67)mV及 ( 79 0 5± 7 0 4 )ms,用药后分别为( 2 6 87± 0 73 )mV及 ( 77 5± 7 170 )mV(P >0 0 5 ) ;用药2 0 0 1 0 2 15收稿 ,2 0 0 1 0 4 13修回1 贵州省人民医院心内科 ,贵阳 5 5 0 0 0 22 包头钢铁职工医院 ,包头 0 14 0 0 0作者简介 :李 屏 ,女 ,36岁 ,医学硕士 ,副主任医师。Tel:0 85 1 5 934 319,E mail:lipingb @hotmail.com ;曾秋棠 ,男 ,36岁 ,医学博士 ,副教授 ,硕士生导师前MAPD5 0、MAPD90、ERP分别为 ( 97 5± 6 770 )ms、( 12 3 5± 5 80 )ms、( 111± 13 5 0 )ms,用药后分别为 ( 12 4 5± 8 96)ms、( 15 3± 7 5 3 )ms、( 14 2± 13 3 7)ms (P <0 0 1) ;实验组用药前MAPA及MAPD2 0分别为 ( 2 6 5 8±1 0 3 )mV及 ( 75± 5 77)ms。

别隐品碱抗心律失常作用及其单相动作电位的作用

目的观察别隐品碱(ALL)的抗动物心律失常作用。方法以氯仿诱发小鼠室颤、以CaCl2-ACh混合液诱发小鼠心房纤颤、肾上腺素致豚鼠心律失常,以乌头碱诱发的豚鼠左室乳头肌收缩节律改变,选择大鼠结扎冠状动脉前降支,观察ALL抗心律失常的效应。记录豚鼠和大鼠心脏的动作电位和单相动作电位。结果 ALL能明显降低氯仿诱发小鼠室颤率,应用30,100 mg／kg的ALL后,CaCl2-ACh混合液诱发小鼠心房纤颤或扑动的发生率从 100％降低到53．3％和33．3％。ALL使肾上腺素致豚鼠心律失常的持续时间降低,并对乌头碱诱发的大鼠心室乳头肌收缩节律失常有明显拮抗效应。ALL可明显延长其心脏的动作电位时程和不应期,这可能是其抗心律失常效应的电生理基础。结论 ALL呈现出多种抗实验性心律失常的作用。

生脉注射液抗家兔缺血性心律失常的作用

目的研究生脉注射液抗家兔心肌缺血所致心律失常的作用。方法用同步记录家兔闭胸体表心电图、心内膜和心外膜单相动作电位的技术,研究生脉注射液抗心肌缺血所致心律失常的作用。结果在室性快速性心律失常发生的过程中,家免的心内膜和心外膜单相动作电位振幅降低,0期去极化速率减慢,电位呈三角样变化。结论生脉注射液使家兔的单相动作电位振幅增高,0期去极化速率加快,垂体后叶素所致心肌缺血后的电生理改变程度减轻;随给药时间的延长,心内膜和心外膜心肌兴奋的传导性和活动的同步作用增强,心脏的电稳定性增高,进而阻止在心肌缺血基础上的折返运动形成,避免心律失常的发生。

川芎嗪对兔室性心律失常心外膜单相动作电位的影响

目的探讨川芎嗪(TMP)对兔缺血性室性心律失常时心外膜单相动作电位(MAP)的影响。方法 20只家兔,随机分为单纯缺血组(n=10)和TMP组(n=10),采用闭胸记录心外膜MAP和心电图的改变,观察心肌缺血背景下致心律失常前后MAP参数的变化。结果在单纯缺血组室性快速性心律失常发生过程中,与缺血前相比,心外膜MAP振幅(MAPA)降低(P<0.01),0相最大上升速率(Vmax)减慢(P<0.01),MAP复极化50%和90%的时程(MAPD50和MAPD90)缩短(P<0.01);而在TMP组,用TMP预处理后,与缺血前相比,心外膜MAPA、Vmax、MAPD50和MAPD90均无明显变化;与单纯缺血组相比,室性心律失常发生率降低(P<0.05),心外膜MAPA和Vmax增加(P<0.05),MAPD50和MAPD90延长(P<0.01)。结论 TMP能减轻缺血后MAP改变程度,具有抗缺血性室性心律失常作用,其机制可能与其抑制折返形成有关。

苄基四氢巴马汀对缺血—复灌与单相动作电位的影响

苄基四氢巴马汀(benzyltetrahydropalmatin,BTHP)是四氢巴马汀的衍生物,剂量1～10mg/kg有抗多种实验性心律失常的作用,对大鼠心缺血—复灌所致心律失常也有效。本文观察BTHP对在位猫心缺血—复灌时单相动作电位(MAP)变化的影响。

索他洛尔诱导尖端扭转型室性心动过速发生机制的实验研究

目的 :探讨索他洛尔诱导在体心脏尖端扭转型室性心动过速 (Td P)的发生机制。 方法 :同步记录 12只开胸兔左心室心外膜心肌、中层心肌、心内膜心肌的单相动作电位 ,静脉注射索他洛尔后 ,探讨Td P的发生机制。 结果 :12只兔共诱发了 19次 Td P,Td P的第 1个室性激动均起自单相动作电位上早期后除极 (EAD)的峰值 ,其中10次 Td P其后的室性激动均由前一个室性激动的 EAD引起 ,最后一个室性激动复极电位降至阈下后 Td P终止 ;其余 9次 Td P第 1个室性激动之后的室性激动在与之相应的各层心肌的单相动作电位上均无 EAD。 结论 :EAD是 Td P发生的始动因素 ,EAD产生的触发活动和三层心肌间复极离散度的明显增加在 Td P的维持中起重要作用。

蟾蜍高钾血症动物模型实验方法的研究

目的利用在体蟾蜍心脏建立模拟高钾血症(hyperkalemia)动物模型,观察高血钾对蟾蜍Ⅱ导联心电图(electrocardio-graph,ECGⅡ)及心室肌单向动作电位(monophasic action potential,MAP)的影响。方法本实验经咽淋巴囊注射10%氯化钾(KCl)使蟾蜍心肌细胞外液中钾含量急剧升高,同步记录MAP和ECGⅡ。结果注射10%KCl10min后MAP的二相(坪)动作电位时程延长,心率减慢,ECG显示P-R间期延长,QRS波群增宽变低,T波明显高尖,部分动物T波变低或消失。与给药前相比各记录指标差异显著(P<0.05)。结论咽淋巴囊注射10%KCl可致蟾蜍急性高钾血症且ECG改变与哺乳动物高钾血症有相似之处。

心电图U波与左心室中层心肌关系的实验研究

利用单相动作电位记录技术 ,同步记录 16只兔子左心室心外膜下、中层和心内膜下心肌的单相动作电位 ,以索他洛尔作为工具药 ,研究心电图 U波的起源。结果发现 :1应用索他洛尔 1.5 mg/ kg后心电图上出现 U波 ,随着索他洛尔剂量的增加 ,U波更加明显。 2索他洛尔明显延长中层心肌的复极时程 ,心外膜下心肌的复极时程与体表心电图 T波的顶点相一致 ,而中层心肌的复极时程与 U波的终点相一致。提示 U波的产生可能是由于中层心肌复极延迟所致。

静脉注射索他洛尔的临床心脏电生理作用及安全性

目的：研究静脉注射索他洛尔（ｓｏｔａｌｏｌ）对非器质性心脏病患者的心脏电生理作用及安全性。 方法：受试者１０例，１５分钟内静脉注射盐酸索他洛尔０．８ ｍ ｇ／ｋｇ，继以０．６ ｍ ｇ／（ｋｇ·ｈ）匀速静脉泵入。于用药前和静脉泵入１５ 分钟时分别行心脏电生理检查并记录右心室单向动作电位。 结果：用药后窦性周长、窦房结恢复时间和校正的窦房结恢复时间延长（Ｐ＜ ０．０５），窦房传导时间不变。ＡＨ间期及房室结顺传文氏周期延长（Ｐ＜ ０．０１）。心电图ＰＲ、ＱＴ、校正ＱＴ及ＪＴ间期均延长（Ｐ＜ ０．０５），ＱＲＳ间期不变。心房、房室结及心室相对不应期、功能不应期及有效不应期（ＥＲＰ）延长。右心室单向动作电位时间（ＭＡＰＤ９０ ）延长（Ｐ＜ ０．０１），而ＥＲＰ／ＭＡＰＤ９０不变。未发现明显不良反应。 结论：静脉索他洛尔兼有Ⅱ类及Ⅲ类抗心律失常作用，国人对０．８ ｍ ｇ／ｋｇ 耐受性良好。

右美托咪定对家兔离体心脏缺血-再灌注时心肌单相动作电位及跨室壁复极离散度的影响

目的观察右美托咪定对家兔离体心脏缺血-再灌注心肌动作电位及跨室壁复极离散度的影响,探讨其对缺血-再灌注心肌电生理特性的作用。方法健康成年家兔18只,体重（2.0±0.5）kg,成功制备Langendorff离体心脏灌注模型,K-H液平衡灌注15min后,随机分为三组,每组6只：空白对照组（C组）：持续平衡灌注37℃K-H液150min;缺血-再灌注组（IR组）：K-H液继续灌注15min后停止,注射Thomas液（4℃,10 ml/kg）使心脏停搏60 min,心脏周围用低温（4℃）Thomas液保护,30min半量复灌Thomas液（4℃,5ml/kg）,60min时复灌K-H液;右美托咪定组（DEX组）：于K-H液及Thomas液中加入右美托咪定（25ng/ml）,余同IR组。记录平衡灌注15min（T0）、继续灌注15min/平衡30min（T1）、复灌30min/平衡120min（T2）、复灌60min/平衡150min（T3）的HR及三层心肌[内膜（Endo）、中膜（Mid）、外膜（Epi）]单相动作电位振幅（monophonic action potential amplitude,MAPA）,0相最大上升速率（Vmax）,90%单相动作电位时程（monophonic action potential duration,MAPD90）并计算跨室壁复极离散度（transmural dispersion of repolarization,TDR）,观察心脏复灌时心律失常、复跳时间,均不使用药物恢复心律。结果 DEX组心脏复跳时间（16.67±3.78）s明显短于IR组（46.33±7.29）s（P〈0.05）;心脏复跳时IR组有6例发生心律失常,2min内有2例恢复正常节律;DEX组有2例发生心律失常,2min内有1例恢复正常节律。与T0时比较,T2、T3时IR组,T1-T3时DEX组HR明显减慢（P〈0.05）;与T1时比较,T2、T3时DEX组HR明显减慢（P〈0.05）;与T2时和C组比较,T3时DEX组HR明显减慢（P〈0.05）;T1-T3时DEX组HR明显慢于IR组（P〈0.05）。与T0时比较,T1时DEX组Mid部位,T2、T3时DEX组Epi、Mid、Endo部位的MAPD90明显延长（P〈0.05）。与T1时比较,T3时DEX组Epi、Mid、Endo部位的MAPD90明显延长（P〈0.05）;T3时DEX组Mid部位的MAPD90明显长于C组（P〈0.05）;T2、T3时DEX组Epi、Mid、Endo部位的MAPD90明显长于IR组（P〈0.05）。与T0时和C组比较,T2、T3时IR组,T1-T3时DEX组TDR明显增大（P〈0.05）;T2、T3时DEX组TDR明显小于IR组（P〈0.05）。结论右美托咪定能够延长MAPD、抑制缺血-再灌注损伤后心肌复极不均一性,具有稳定缺血-再灌注心肌电生理特性的作用。

粉防己碱抗氯化铯诱发家兔在体心脏早后除极及心律失常的作用

目的 :研究粉防己碱 (Tet)抗氯化铯 (CsCl)诱发触发活动及触发性心律失常作用。方法 :14只家兔分对照组和Tet组 ,Tet组给予Tet 0 5mg kg min共 10min ,对照组给予生理盐水 ,然后给予CsCl1 5mmol kg静注 ,给药前后记录心电图和右室心内膜MAP。结果 :Tet组和对照组均诱发EAD ,但Tet组EAD幅度低于对照组 ,室性心律失常发生率低于对照组。结论 :Tet有抗CsCl诱发EAD及室性心律失常作用。其机制可能是Tet抑制慢钙通道 ,减少内向电流。