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。     

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。     

贝那普利对扩张型心肌病中层心肌细胞动作电位时程的影响

目的探讨贝那普利对扩张型心肌病（DCM）中层心肌细胞动作电位时程的影响及其抑制莹性心律失常。方法制作DCM家兔模型，并给予贝那普利干预，然后测定其室颤阈值（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DCM治疗组（DCM＋贝那普利）与DCM对照组相比，治疗组VFT阈值升高，三层心肌APD90均缩短，以中层心肌APD90缩短更为明显，TDR减小。结论贝那普利能抑制DCM室性心律失常的发生，间接地减小三层心肌跨室壁复极不均一性是重要机制。     

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。     

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。     

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。24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1.0mg/kg,3.0mg/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（TdP）的发生率亦更高。     

β受体阻滞剂对在体犬跨室壁复极离散度影响的研究

用单相动作电位记录技术 ,在应用β受体阻滞剂前、后刺激交感神经过程中 ,同步记录 18只开胸犬基础及急性缺血条件下左心室游离壁心外膜、中层心肌和心内膜心肌细胞的单相动作电位。结果表明交感神经刺激使跨室壁复极离散度 (TDR)减小。急性缺血可使 TDR增加 ,交感神经刺激使 TDR进一步由 (5 4± 7) ms增加到 (83± 13) m s (P<0 .0 1) ,而且可以在中层心肌诱发出早期后除极 (EAD)。β受体阻滞剂可完全阻断交感神经刺激的作用     

复极时程和跨室壁复极离散在尖端扭转型室性心动过速中的作用

目的:探讨复极时程和跨室壁复极离散(TDR)在尖端扭转型室性心动过速(TdP)发生的作用. 方法:32只兔随机等分为4组,低浓度索他洛尔组(10 μmol/L),高浓度索他洛尔组(100 μmol/L),低浓度奎尼丁组(1 μmol/L),高浓度奎尼丁组(10 μmol/L). 采用Langendorff技术离体兔心脏灌流,同步记录用药后三层心肌的单相动作电位(MAP)和TDR,观察早期后除极(EAD)、TdP的发生情况. 结果:索他洛尔浓度依赖性地延长三层心肌MAP时程(MAPD)和TDR,高浓度索他洛尔组诱发EAD,TdP分别为8只和6只,而低浓度组诱发EAD,TdP分别为4只和0只. 奎尼丁浓度依赖性地延长三层心肌MAPD,但逆浓度依赖性地延长TDR,高浓度奎尼丁组诱发EAD,TdP分别为7只和1只,而低浓度组诱发EAD,TdP分别为6只和4只. 结论:与TdP的发生密切相关的主要是TDR,而不是复极时程.     

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。     

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。     

普萘洛尔治疗长QT综合征的电生理机制探讨

目的：观察普萘洛尔对家兔跨左室壁不同部位心肌细胞电生理特性的影响，探讨普萘罗尔治疗长QT综合征（LQTS）的电生理机制。方法：采用标准玻璃微电极记录技术，记录心外膜心肌（epicardium，Epi）、中层心肌（mid—myocardium，Mid）和心内膜心肌（endocardium,Endo）的跨膜动作电位（transmembrance action potential，TAP）。用基础周长（basic cycle length，BCL）为2000m刺激心肌标本，观察不同浓度的普萘洛尔对三种心肌TAP的影响。结果：1．普萘洛尔浓度依赖性缩短d—sotalol灌流的三层心肌的APD90，与Epi和Endo相比，Mid的APD90缩短更明显，使TDR降低，且随着剂量的增加这种作用更为显著。2．普萘洛尔浓度依赖性地抑制d—sotalol诱导的早期后除极（Early afterdepolarization，EAD）。结论：普萘洛尔降低三层心肌间的复极离散度和抑制早期后除极是普萘洛尔治疗LQTS的电生理机制。     

Experimental Study of the Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization under Acute Myocardial Ischemia in Vivo

The electrophysiologic heterogeneity of the ven-tricular myocardium is an important factor of devel-oping ventricular arrhythmia.Under the pathologiccondition,thedistribution and thefunction of the au-tonomic nerves,especially the sympathetic nerve,can produce the heterogeneity in the myocardium,which can accelerate the electrophysiologic hetero-geneity of the ventricular myocardium.Acute my-ocardial ischemia can induce the dysfunction of theautonomic nerve endings,resulting in the hetero-gene…     

Experimental study of the effect of autonomic nervous system on the transmural dispersion of ventricular repolarization under acute myocardial ischemiain vivo

Summary The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD₉₀ and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55±8 ms to 86±15 ms during sympathetic stimulation (P<0.01). The TDR (53±9 ms) during parasympathetic stimulation was not significantly different from that of the control (55±8 ms) (P>0.05). The EAD was elicited in the Mid of 2 dogs (16%) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58%) during sympathetic stimulation (P<0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolarization and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia. Zhang Cuntai, male, born in 1963, Associate Professor     

Effect of Autonomic Nervous System on the Transmurai Dispersion of Ventricular Repolarization in Intact Canine

Summary: The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid)and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall in 12 open-chest dogs. MAPD90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD90 of Epi, Mid and Endo before autonomic nervous stimulation were 278±11 ms,316± 16 ms and 270± 12 ms respectively, the MAPD90of Mid was significantly longer than that of Epi or Endo (P＜0.01). MAPD90 of Epi, Mid and Endo were shortened by 19±4 ms, 45±6 ms,18± 3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44 ± 4 ms to 15±3 ms (P＜0. 01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41 0%)during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.     

Na+/Ca2+交换体电流在兔左心室壁分布的异质性

目的探讨Na+/Ca2+交换体电流(INa+/Ca2+)在左室肌不同部位的分布特征及其与跨壁复极异质性的关系.方法采用全细胞膜片钳技术,分别记录兔左心室肌内膜下、中层及外膜下细胞的动作电位(AP)、INa+/Ca2+及IK.结果中层细胞AP时程明显长于外膜下细胞(P<0.01);在+40 mV时,外向INa+/Ca2+密度在中层细胞明显大于外膜下及内膜下细胞(P分别＜0.01,0.05);在-100 mV时,内向INa+/Ca2+密度在中层细胞明显大于外膜下(P<0.05);在测试电压为+50mV时,中层细胞的IKs尾电流密度明显小于外膜下细胞(P<0.05), 内膜下、中层及外膜下细胞的IKr尾电流密度无明显区别(P>0.05).结论 INa+/Ca2+与IKs在兔左室肌的分布具有异质性,并导致了跨壁复极异质性的形成.     

Effect of autonomic nervous system on the transmural dispersion of ventricular repolarization in intact canine

Therecentstudieshavefoundasub populationofcells ,namedmidmyocardiumcells(Mcell) ,withuniqueelectrophysiological propertiesinthedeepsubepicardiumoftheventricleofhuman ,canineandotheranimals .TheresearcherssuggestedthattheMcellsnotonlyformthecellularbasisof…     

Electrical heterogeneity of canine right ventricular transient outward potassium currents

Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (Ito1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent Ito1. Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the Ito1 values of the three cell types. Results At 37℃ and using 0.2 Hz and +70 mV depolarizing test potentials, the average peak Ito1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with Ito1 in Epi cells and M cells, the average peak Ito1 in Endo cells was very low, averaged (470±130) pA. Conclusions These results suggest that there are evident differences and potent gradients in Ito1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.     

伊文思兰对兔左室心肌灌注范围显示效果及跨膜动作电位的影响

目的　探讨伊文思兰对于经冠脉灌注的兔左室心肌组织块灌注范围显示效果及跨膜动作电位的影响。方法　制做兔左心室游离壁楔形组织块 ,经回旋支持续灌注台式液。采用浮置的玻璃微电极同步记录内、中、外层心肌细胞跨膜动作电位并记录跨壁心电图。分析伊文思兰灌注前、灌注 30 min后组织块显色情况及不同频率刺激下内、中、外层跨膜动作电位时程和跨壁复极离散度的变化。结果　伊文思兰可清晰显示灌注范围 ,且 30 m in后颜色仍保持不变 ;在 5 0 0～ 4 0 0 0 ms刺激作用下 ,伊文思兰灌注前与灌注 30 m in后动作电位时程、跨壁复极离散度无显著变化 (P>0 .0 5 ) ,灌注过程中组织块无室性心律失常发生。结论　伊文思兰可以作为组织块灌注范围的显示剂     

模拟缺血缺氧对左心室心肌细胞钠电流跨壁异质性的影响

目的 :　研究左心室心肌细胞快钠通道的跨壁异质性及模拟缺血对其的影响。　方法 :采用全细胞膜片钳记录技术直接记录左心室三层心肌细胞的快钠通道电流 (INa) ,并观察模拟缺血缺氧对心肌细胞INa跨壁异质性的影响。　结果 :左心室三层心肌细胞的钠电流特性存在异质性 ,表现为中层 (M )细胞的电流密度 电压关系(I V)曲线最低 ,M细胞的峰值INa是心内膜层 (Endo)和心外膜层 (Epi)的 2倍多 ;M细胞的INa失活最快。模拟缺血后 ,三层心肌细胞的INaI V曲线呈时间依赖性下移 ,M细胞的变化最显著 ;INa稳态失活曲线呈时间依赖性左移 ,以Epi变化最显著 ;模拟缺血 30min时Endo的恢复明显慢于M和Epi。　 结论 :左心室心肌细胞的INa存在跨壁异质性 ;模拟缺血缺氧对INa的跨壁异质性有明显影响。