大豆异黄酮对豚鼠乳头肌动作电位和心肌细胞钠电流的影响

目的 观察大豆异黄酮(soybean isoflavone,SI)对豚鼠乳头肌动作电位的影响和培养心室肌细胞钠电流的作用.方法 采用悬浮玻璃微电极法测定乳头肌的动作电位和全细胞膜片钳方法测定心室肌细胞的钠电流.结果 SI能剂量依赖性地降低乳头肌动作电位幅值(APA),且能同时缩短复极50%及90%水平的动作电位时程(APD50、APD90);SI 0.1μg/ml和1.0μg/m1对心室肌细胞钠电流抑制率是14.39%和23.48%.结论 SI对心肌有负性肌力作用,可使心肌细胞动作电位除极参数降低,动作电位时程缩短,对钠电流的抑制是其负性肌力作用和抗心律失常作用的离子机制之一.     

牛磺酸对甲亢豚鼠心室肌细胞电生理特性的影响

目的观察牛磺酸(Taurine T)对甲状腺机能亢进(以下简称甲亢)豚鼠离体心室肌细胞动作电位的影响,探讨牛磺酸对甲亢豚鼠心室肌细胞电活动的影响及其机制.方法采用微电极技术,引导心室肌细胞动作电位,观察在甲亢状态下牛磺酸对心室肌细胞动作电位各参数的影响.结果 (1)甲亢组豚鼠心室肌细胞动作电位时程(APD20, APD50, APD90, APD)及有效不应期(ERP)显著缩短,甲亢豚鼠心室肌细胞动作电位幅度(APA),零期最大除极速率(Vmax)无显著性变化;(2)加入牛磺酸后,甲亢豚鼠心室肌细胞动作电位时程APD50, APD90, APD显著延长,而APD20及动作电位幅度(APA)无显著变化 ,零期最大除极速率(Vmax)显著降低,ERP显著延长;(3)给甲状腺功能正常组加入牛磺酸后,豚鼠心室肌细胞动作电位时程APD20, APD50, APD90显著缩短,APD亦有缩短,但无显著性差别,ERP显著延长,APA无显著性变化,Vmax显著性降低.结论 (1)较高浓度的牛磺酸可能对甲亢豚鼠的离体心室肌细胞膜的外向(主要是K )电流具有一定的抑制作用;(2)对甲状腺功能正常豚鼠的心室肌细胞,一定程度上,可能促进钾外流;(3)无论是正常组还是甲亢组,在加入牛磺酸后,Vmax均出现显著降低,提示较高浓度的牛磺酸对心室肌细胞的INa也有影响.     

二十二碳六烯酸对大鼠心室肌细胞动作电位和钠通道的影响

目的 探讨二十二碳六烯酸（DHA）对大鼠心室肌细胞动作电位（AP）及钠通道电流（INa）的影响,阐述DHA抗心律失常的机制.方法 用膜片钳技术在全细胞模式下,记录0、20、40、60、80、100和120 μmol/L的DHA对大鼠心室肌细胞AP复极25%、50%和90%时限（APD25、APD50和APD90）,对AP最大上升速率（vmax）、幅值（APA）、超射值（OS）及INa的影响.结果 （1）DHA对APD25、APD50和APD90呈浓度依赖性延长（P＜0.05,n=20）,对vmax、APA和OS的影响差异无统计学意义（P＞0.05,n=20）.（2）DHA对INa呈浓度依赖性阻滞、I-U曲线上移、稳态失活曲线左移、失活后恢复时间延长,对稳态激活曲线无影响.在指令电压-30mV,上述浓度DHA对INa阻滞分别为1.51%±1.32%、21.13%±4.62%、51.61%±5.73%、67.62%±6.52%、73.49%±7.59%和79.95%±7.62%（P＜0.05,n=20）,DHA对INa的半效作用浓度（EC50）为（47.91±1.57）μmol/L.结论 DHA对APD的延长及对钠通道的抑制作用可能是其抗心律失常机制之一.     

稳心颗粒对大鼠心室肌细胞跨膜动作电位的影响

目的观察稳心颗粒对大鼠左室壁跨膜动作电位的影响,从组织水平探讨稳心颗粒抗室性心律失常的机制。方法采用标准玻璃微电极技术,记录大鼠心室肌组织心内膜心肌细胞的跨膜动作电位(TAP)。在基础周长500ms刺激下,分别观察1,5,10,15,20g/L稳心颗粒对标准台式液灌流心肌和含哇巴因台式液灌流心肌TAP的影响。结果①不同浓度的稳心颗粒浓度依赖性的延长动作电位时程(APD)、90%复极化时间(APD90);对动作电位幅值(APA)无影响。②含哇巴因台式液灌流之后,各浓度稳心颗粒使APD、APD90延长,对APA无影响,15g/L的延长作用最显著。对于哇巴因诱发的早期后除极和心律失常,各浓度的稳心颗粒均有抑制作用。结论稳心颗粒对心室肌APD的延长和对触发活动的抑制是其抗心律失常作用的电生理基础。     

别隐品碱抗心律失常效应及其对动作电位的影响

目的研究别隐品碱(ALL)抗心律失常效应及其对心室肌动作电位的影响.方法选择大鼠和豚鼠以静脉给乌头碱、哇巴因和氯化钡造动物心律失常的模型,观察ALL对心律失常的效应,分离豚鼠乳头状肌观察ALL对动作电位的影响.结果ALL(30和100mg/kg)对乌头碱、哇巴因和氯化钡致动物实验性心律失常有良好的对抗作用,使各种试剂诱发的室早、室速、室颤及停搏的剂量增加.ALL可降低动作电位上升幅度(APA)和0相最大上升速率(Vmax).3.0～100.0 μmol/L的ALL以浓度依赖性方式使离体乳头状肌动作单位时程(APD)延长,其中30.0μmol/L的ALL使APD90延长67.5%.结论ALL具有抗实验性心律失常的效应,此效应可能与其影响心肌组织的电生理密切相关.     

长QT综合征复极化离散与早期后除极致心律失常机制的跨壁光学标测研究

目的　尖端扭转性室性心动过速 (室速 )是长QT综合征 (LQTS)的致命性心律失常 ,相关机制的细胞学水平研究还不十分清楚。本文报道对复极化离散和触发机制在尖端扭转性室速发生中的作用的研究结果。方法　动脉灌注的犬左心室楔形心肌块 ,经电压敏感性荧光染色后 ,行跨壁包括百余位点跨膜动作电位的同步光学标测研究。d 索他洛尔、海银花 (ATX Ⅱ)分别用来模拟LQT2和LQT3。对照组、LQT2组、LQT3组各 6块。结果　正常对照组的平均动作电位时限 (APD)为 (2 91± 2 7)ms,跨壁复极化的离散(DOR)为 (2 4± 6 )ms;LQT2组APD为 (35 6± 2 0 )ms,DOR为 (35± 9)ms,与对照组相比差异有显著性 (P <0 0 5 ) ;LQT3组APD为 (6 0 9± 92 )ms,DOR为 (12 1± 85 )ms,与对照组相比差异有显著性 (P <0 0 5 )。在LQT3组 ,早期后除极现象可见于所有类型的心肌细胞 ,但以心内膜和中层心肌细胞多见。触发活动常常起源于中层心肌细胞部位。结论　在LQT条件下 ,跨壁动作电位不均一地延长是导致复极化离散的重要原因 ,为心律失常的发生提供了基质。早期后除极诱导的触发活动触发了尖端扭转性室速     

高血压左室肥厚消退后心肌细胞跨膜电位变化的实验研究

目的　观察高血压左室肥厚消退后心肌细胞跨膜电位的变化。方法　 12周龄自发性高血压大鼠 (SHR) ,分别饲服尼群地平或卡托普利 14周 ,以同龄WKY及不经治疗的SHR鼠为对照。采用传统浮置式玻璃微电极记录在体心脏心室肌细胞的动作电位幅度 (APA) ,静息电位 (RMP) ,动作电位时限 (APD) ,及复极 90 %、75 %、5 0 %、2 5 %时的动作电位时限 (APD90 、APD75 、APD5 0 、APD2 5 ) ,并计算APD的离散度。结果　 (1)左室肥厚心肌细胞APD及其离散性均明显大于对照组 ;(2 )尼群地平和卡托普利治疗消退左室肥厚后 ,左心室肌细胞APD缩短及APD离散性减少。结论　伴随心肌肥厚的消退 ,心室肌细胞电生理异常好转。     

钠通道阻断剂对模拟在体犬LQT3跨室壁复极离散影响的实验研究

目的:观察心率减慢时模拟体内长QT综合征第3型(LQT3)动作电位时程(APD)和跨室壁复极离散(TDR)的变化及钠通道阻断剂美西律对这种变化的影响,为先天性LQT3室性心律失常的防治提供实验依据。方法:采用自制电极记录犬体内左心室前壁跨室壁单相动作电位,静脉注射海葵毒素(ATX-Ⅱ)模拟LQT3,消融窦房结后改变心房起搏周长(PCL)控制心室率。结果:静脉注射ATX-Ⅱ(3μg／kg)后成功模拟出LQT3模型; PCL为500 ms和1000 ms时ATX-Ⅱ使TDR均显著性增加[分别为(20±4)ms:(41±9)ms和(39±5)ms:(83 ±10)ms,均P<0．05],但PCL为1 000 ms比500 ms时TDR的增加幅度(ATDR)更为明显[(44±13);(20± 12)ms,P<0．05],伴随起源于中层心肌细胞的早期后除极和自发性室性心动过速发生;美西律(20μg／kg)能逆转ATX-Ⅱ的这种电生理作用。结论:LQT3室性心律失常的发生呈慢心室率依赖性,美西律可能对先天性 LQT3猝死的防治有一定的作用。     

低渗性肿胀对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响

观察单个豚鼠心室肌细胞动作电位和主要复极期电流延迟整流钾电流(IK)的变化,探讨急性心肌缺血再灌注室性心律失常发生的离子机制。采用全细胞膜片钳记录技术,观察低渗液(200mOsm/kg)灌流胶原酶分离的单个豚鼠心室肌细胞发生肿胀后的动作电位各参数的变化,同时记录IK及其快、慢两种激活成分(IKr及IKs)的变化。结果:低渗液灌流后心室肌细胞迅速发生肿胀,动作电位幅度(APA)、静息膜电位(RMP)及阈电位水平无明显变化;而动作电位时程(APD)在600,1000和3000ms三种基础起搏周长(BCL)刺激时均缩短(P<0.05),尤以APD复极达50%和90%时缩短更为明显。APD生理性频率适应性消失且离散度增大。低渗性肿胀状态下IK电流幅度在3000ms长去极化保持时间(主要成分为IKs)刺激时从1134.33±150.17pA增加至1621.98±234.95pA(P<0.001,n=10);而在100ms短去极化保持时间(主要成分为IKr)刺激时从693.44±96.44pA降低至294.06±71.79pA(P<0.05,n=8);并且使IK的IV曲线向上移位。结论:低渗性肿胀的心室肌细胞IK特别是IKs的增加是引起APD缩短的重要因素,是急性心肌缺血再灌注室性心律失常发生的离子机制之一。     

兔右室流出道心肌细胞动作电位及钠钙交换尾电流特性

目的研究兔右室流出道(RVOT)心肌细胞动作电位及钠钙交换尾电流(INCX,tail)相关特性,探讨源于RVOT室性心律失常的发生机制。方法采用全细胞膜片钳技术记录兔右室(RV)游离壁和RVOT心肌细胞的动作电位,在不更换细胞及电极内液情况下连续记录INCX,tail,对比分析两者动作电位和INCX,tail特性。结果兔RVOT心室肌细胞动作电位复极时程(APD)的变异程度大于RV游离壁心肌细胞。在RVOT心肌细胞记录到早期后除极及显著延长的APD。动作电位显著延长及后除极的RVOT心肌细胞所对应的INCX,tail到达峰值时程较动作电位正常的细胞延迟,并且电流强度大于RV游离壁对照组心肌细胞(P<0.05)。结论 RVOT心肌细胞APD变异程度大,而且APD显著延长的RVOT细胞INCX,tail到达峰值时程延迟及相应电流显著增大,这是RVOT部位好发触发活动的重要机制。     

胺碘酮慢性作用对兔心室肌细胞L型钙通道电流和跨壁动作电位相关性研究

目的 从单个心室肌细胞L型钙通道电流时间常数(τ)和组织块跨壁动作电位复极90%时程(APD90),探讨胺碘酮慢性作用抗心律失常的可能细胞电生理机制.方法 健康兔口服胺碘酮80 mg·kg-1·d-1共4周,记录离体兔带血管心室肌组织块跨膜心室肌细胞动作电位后分离心室肌细胞,记录单细胞L型钙通道电流τ,比较对照组、胺碘酮组及索他洛尔组干预下τ与APD90比值(τ/APD90)变化.结果 对照组τ为(98±8)ms(n=10)、APD90为(220±10)ms(n=5)、τ/APD90为0.44±0.03.与对照组相比,胺碘酮组τ明显延长[为(164±8)ms,n=8,P＜0.05],APD90亦明显延长[为(321±12)ms,n=5,P＜0.05],τ/APD90较对照组增加(分别为0.51±0.03与0.44±0.03,P＜0.05).索他洛尔(3×10-5mmoL/L)组与对照组相比,τ明显延长[为(128±7)ms,n=8,P＜0.05],但因APD90延长较著[为(405±13)ms,n=4,P＜0.01],使τ/APD90较对照组明显减少(分别为0.32±0.05与0.44±0.03,P＜0.05).索他洛尔+胺碘酮组的τ为(150±12)ms、APD90为(355±11)ms(n=4),与索他洛尔组比较,τ/APD90增加(为0.44±0.02,P＜0.05),与对照组相比,差异无统计学意义(P＞0.05).结论 心室肌细胞膜L型钙通道电流的τ/APD90大小与胺碘酮慢性作用相关,这为胺碘酮慢性作用的安全性提供了一种可能解释.     

兔界嵴细胞离子通道特性研究

目的研究生理状态下及异丙肾上腺素灌流对兔界嵴(CT)与梳状肌(PM)细胞动作电位(AP)及钠电流(INa)、短暂外向钾电流(Ito)、L型钙电流(ICa-L)、延迟整流钾电流(IK)及内向整流性钾电流(IK1)的影响,探讨CT与房性心律失常的关系。方法酶解法分离兔CT及PM细胞,利用全细胞膜片钳技术,记录生理状态下及异丙肾上腺素灌流后CT与PM细胞AP及INa、Ito、ICa-L、IK及IK1的变化。结果①生理状态下,CT细胞动作电位时程(APD)较长,可见明显的平台期;PM细胞AP形态与普通心房肌细胞相似,1期复极迅速,平台期短,类似三角形。②生理状态下,CT细胞Ito电流密度比PM细胞明显降低(7.13±0.38 pA/pF vs 10.70±0.62 pA/pF,n=9,P<0.01),而INa、Ito、ICa-L、IK及IK1则无明显差别。③异丙肾上腺素灌流时CT与PM细胞APD20、APD50、APD90均延长(n=8,P<0.01);指令电位+50 mV时,CT与PM细胞Ito电流密度均减少(n=9,P<0.01)而IK均增加(n=8,P<0.05);指令电位+10 mV时,CT与PM细胞ICa-L电流密度均增加(n=9,P<0.01);IK1在两种心肌细胞均无明显差异。结论 CT与PM细胞AP差异与Ito有关。异丙肾上腺素灌流时ICa-L与IK增强,Ito抑制使CT与PM细胞APD延长,触发机制可能是CT参与房性心律失常的机制之一。     

Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo

OBJECTIVE: Mutations in the cardiac sodium channel gene SCN5A are responsible for type-3 long QT disease (LQT3). The genesis of cardiac arrhythmias in LQT3 is multifaceted, and the aim of this study was to further explore mechanisms by which SCN5A mutations lead to arrhythmogenesis in vivo. METHODS: We engineered selective cardiac expression of a long QT syndrome (LQTS) mutation (N1325S) in human SCN5A and generated a transgenic mouse model, TGM(NS31). RESULTS: Conscious and unrestrained TGM(NS31)L12 mice demonstrated a significant prolongation of the QT-interval and a high incidence of spontaneous polymorphic ventricular tachycardia (VT) and fibrillation (VF), often resulting in sudden cardiac death (n=52:156). Arrhythmias were suppressed by mexiletine, a sodium channel blocker for the late persistent sodium current. Action potentials (APs) from TGM(NS31)L12 ventricular myocytes exhibited early afterdepolarizations and longer 90% AP durations (APD90=69 +/- 5.9 ms) than control (APD90=46.7 +/- 4.8 ms). Voltage-clamp experiments in transgenic myocytes revealed a peak inward sodium current (INa) followed by a slow recovery from inactivation. After mexiletine application, transgenic ventricular APDs were shortened, and recovery from inactivation of INa was enhanced. These suggest that the N1325S transgene is responsible for the abnormal signals present in transgenic cells as well as the genesis of lethal arrhythmias in mice. Interestingly, transgenic but not wild-type myocytes displayed longer APDs with a shortening of CLs. CONCLUSIONS: Our findings show that a new model for LQTS has been established, and we report on an arrhythmogenic mechanism that, unlike other SCN5A mutations, results in poor restitution of APD with increasing rate as a possible substrate for arrhythmogenesis.     

Reduced repolarization reserve in ventricular myocytes from female mice

OBJECTIVE: Cardiac repolarization is prolonged and repolarization reserve (RR) is diminished in female rabbits and humans, compared to males. Reduced RR is evidenced by the relatively greater increase in ventricular action potential duration (APD) in myocytes from females in response to drugs that block repolarizing K(+) currents. Mice are an increasingly important experimental model animal for cardiovascular research, but gender-dependent differences have not been reported for repolarization in murine ventricular myocytes. METHODS: APD and repolarizing K(+) currents were measured in isolated ventricular myocytes from adult littermate male and female mice. Repolarizing K(+) currents were dissected into transient (I(to)) and sustained (I(sus)) components and the selective I(sus) antagonist FK506 was used to probe for differences in RR. RESULTS: Under control conditions APD at 50% (APD(50)) and at 90% (APD(90)) repolarization was significantly longer in females (APD(50)=15 +/- 3 ms, n=6 and APD(90)=63 +/- 6 ms, n=6) compared to males (APD(50)=8 +/- 2 ms, n=7 and APD(90)=42 +/- 9 ms, n=7) at 1.0 Hz. At 0.3 Hz stimulation frequency APD(90), but not APD(50), was significantly longer in females (APD(50)=12 +/- 2 ms and APD(90)=54 +/- 5 ms, n=10) compared to males (APD(50)=11 =/- 2 ms and APD(90)=47 +/- 7 ms, n=10). FK506 treatment (25 microM) selectively and equally inhibited I(sus) in all cells, and significantly increased APD(50) and APD(90) in males and females at 0.3 and 1.0 Hz. However, increases in APD(50) and APD(90) (0.3 and 1.0 Hz) in response to FK506 were significantly greater in myocytes from females compared to males. Voltage clamp measurement of I(to) and I(sus) revealed that males had a relatively more prominent I(to) while females exhibited a more prominent I(sus). CONCLUSIONS: Ventricular action potential repolarization is prolonged in myocytes from female compared to male mice. Female mice have reduced RR that is unmasked by FK506. These findings suggest that gender is an important variable for cardiovascular studies using mice.     

The ionic mechanisms of long QT interval in diabetic rabbits

Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.     

二十二碳六烯酸对大鼠心室肌细胞钠通道和瞬时外向钾通道的影响

目的 研究二十二碳六烯酸(DHA)对大鼠心室肌细胞钠通道电流(INa)和瞬时外向钾通道电流(Ito)的动力学影响.探讨DHA抗心律失常的机制.方法 采用膜片钳技术在全细胞模式下,记录20、40、60、80、100和120μmol/L DHA对大鼠心室肌细胞INa和Ito的影响.结果 (1)DHA对INa呈浓度依赖性阻滞,使稳态失活曲线左移、失活后恢复时间延长,对稳态激活曲线无影响.在指令电压-30 mV,上述浓度DHA对INa阻滞分别为(1.51±1.32)%、(21.13±4.62)%、(51.61±5.73)%、(67.62±6.52)%、(73.49±7.59)%和(79.95±7.62)%(P<0.05,n=20),DHA对INa的半效作用浓度为(47.91±1.57)μmol/L.(2)DHA对Ito呈浓度依赖性阻滞,使稳态失活曲线左移、失活后恢复时间延长,对稳态激活曲线无影响.在指令电压+70 mV,上述浓度DHA对Ito阻滞分别为(2.61 ±0.26)%、(21.79±4.85)%、(63.11±6.57)%、(75.52 ±7.26)%、(81.82 ±7.63)%和(84.33±8.25)%(P<0.05,n=20),DHA对Ito的半效作用浓度为(49.11±2.68)μmol/L.结论 DHA对钠通道和瞬时外向钾通道的抑制作用可能是其抗心律失常机制之一.

Abstract：

Objective To investigate the effects of docosahexaenoic acid(DHA)on sodium channel current(INa)and transient outward potassium channel current(Ito)in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA.Methods INa and Ito of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature.Effects of DHA at various concentrations(0,20,40,60,80,100 and 120 μmol/L)on INa and Ito were observed.Results (1) INa was blocked in a concentration-dependent manner by DHA,stably inactivated curves were shifted to the left,and recover time from inactivation was prolonged while stably activated curves were not affected by DHA.At-30 mV,INa was blocked to(1.51 ±1.32)%,(21.13±4.62)%,(51.61 ±5.73)%,(67.62 ±6.52)%,(73.49±7.59)%and(79.95±7.62)%in the presence of above DHA concentrations(all P<0.05,n=20),and half-effect concentration(EC50)of DHA on INa was(47.91±1.57)μmol/L(2) Ito were also blocked in a concentration-dependent manner by DHA,stably inactivated curves were shifted to the left,and recover time from inactivation was prolonged with increasing concentrations of DHA,and stably activated curves were not affected by DHA.At+70 mV,Ito was blocked to(2.61 ±0.26)%,(21.79±4.85)%,(63.11 ±6.57)%,(75.52 ±7.26)%,(81.82 ±7.63)%and(84.33±8.25)%,respectively,in the presence of above DHA concentrations(all P<0.05,n=20),and the EC50 of DHA on Ito was(49.11±2.68)μmol/1.Conclusion The blocking effects of DHA on APD and Ito may serve as one of the anti-arrhythmia mechanisms of DHA.     

绝对不应期电刺激对心力衰竭豚鼠心室肌细胞动作电位时程和L型钙电流的影响

目的 探讨绝对不应期电刺激(ARPES)对健康和心力衰竭豚鼠心室肌细胞(分别简称NVM和FVM)动作电位(AP)时程(APD)和L型钙电流(ICa-L)的影响。方法 应用膜片钳技术中电流钳,首先记录基础刺激S1所诱发的AP(APS1),与S1延迟10 ms给予ARPES,记录ARPES给予后的AP(APARPES),比较APS1和APARPES的APD的值,以APD30、APD50和APD90代表动作电位复极30%、50％和90％时的APD值。分别以APS1和APARPES为测试电压,记录AP电压钳下的细胞膜ICa-L。结果(1)在NVM和FVM,ARPES应用后APD均明显延长,以APD30和APD50最为显著(P<0.01)。(2)在NVM,与APS1电压钳记录的ICa-L相比,APARPES电压钳记录的ICa-L电流强度有一过性的减弱和继发增强,但其单位膜电容下的电流强度的整合值略有降低(P<0.05)。在FVM,与APS1电压钳记录的ICa-L相比,APARPES电压钳记录的ICa-L电流强度的减弱程度明显减少,其单位膜电容下的电流强度的整合值是增加的(P<0.01)。结论 ARPES延长NVM和FVM的APD,对NVM和FVM的ICa-L具有不同的影响。     

替米沙坦对牵张刺激乳大鼠心房肌细胞短暂外向钾电流和动作电位的影响

目的探讨替米沙坦对牵张刺激乳大鼠心房肌细胞瞬时外向钾电流（Ito）和动作电位（AP）的影响。方法利用胰酶与Ⅱ型胶原酶混合酶解,并结合差速贴壁和5-溴脱氧尿嘧啶核苷处理得到纯化的乳大鼠心房肌细胞。实验分对照组、牵张组、替米沙坦（1μmol/L）组。采用全细胞膜片钳技术分别记录三组Ito和AP。结果在＋20~＋60 mV刺激电压水平,Ito电流密度（pA/pF）：牵张组低于对照组[＋20 mV和＋60 mV分别为（0.8±0.3）vs（2.1±0.8）和（1.6±0.4）vs（12.1±3.0）;P均〈0.01],替米沙坦组[＋20 mV和＋60 mV分别为（1.4±0.3）和（6.7±1.3）较牵张组增大,P均〈0.01]。牵张组AP复极50%、90%时程（APD50、APD90）较对照组明显缩短[（9.6±1.3 ms）vs（15.5±2.4）ms,（29.9±2.9）ms vs（56.3±3.6）ms,P均〈0.01,n=9],替米沙坦组[APD50、APD90分别为（11.7±2.0）和（41.4±4.6）ms]较牵张组APD延长（P均〈0.05）。结论牵张刺激可降低乳大鼠心房肌细胞Ito电流密度、缩短APD;替米沙坦干预可抑制牵张刺激的此作用。     

长期口服缬沙坦对心肌梗死后室性心律失常的影响 (英文)

目的：探讨长期口服血管紧张素 II的1型受体拮抗剂缬沙坦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只新西兰大白兔随机分为假手术对照组（n＝8）、心肌梗死组（n＝8）和缬沙坦组（n＝8）。假手术对照组只开胸不结扎左冠状动脉前降支,心肌梗死组和缬沙坦组分别结扎左冠状动脉前降支。缬沙坦组术后第二天用缬沙坦（10 mg·kg^-1·d-1）灌胃,三组共喂养12周。三组分别在心肌梗死前、梗死12周后记录左心室内、中、外层心室肌细胞单相动作电位（MAP）,并记录心肌梗死12周后诱发的恶性心律失常次数。结果：1.心肌梗死12周后,缬沙坦组室速/室颤（VT/VF）的发生次数较心肌梗死组显著减少[（3.1±0.8）次比（12.7±1.5）次,P＜0.05];2.心肌梗死组左室三层心肌细胞从MAP起始到复极完成90%的时间（APD90）较心肌梗死前明显延长[（259.2±22.1）ms,（288.0±25.8）ms,（244.6±22.6）ms 比（230.1±23.2）ms,（244.2±23.4）ms,（229.0±21.7）ms,P＜0.05或＜0.01];缬沙坦组左室三层心肌细胞APD90与心肌梗死前相比没有明显差异（P 均＞0.05）;且心肌梗死组跨壁复极离散度（TDR）较假手术对照组、缬沙坦组明显延长[（37.2±10.2）比（18.8±6.2）比（23.9±7.7）,P＜0.05或＜0.01];缬沙坦组与假手术对照组之间 TDR比较无显著性差异（P＞0.05）。结论：长期口服缬沙坦明显降低兔心肌梗死后恶性室性心律失常的发生次数,这可能与改善兔心肌梗死后跨壁复极离散度有关。