钾离子通道亚单位mRNA在犬左右心室中层心肌中的表达

目的研究犬左右室中层心肌短暂外向钾电流(Ito)、延迟整流钾电流缓慢激活成分(Iks)亚单位mRNA的表达情况,探讨左右室复极异质性的可能分子机制。方法应用逆转录-聚合酶链反应(RT-PCR)半定量分析犬左右室中层心肌Ito的α亚单位(Kv4.3)、β亚单位(KchIP2)、Iks的α亚单位(KvLQT1)mRNA的表达量(以β-actin为内参照)。结果Kv4.3 mRNA水平在左右室中层心肌中表达没有显著性差异(P>0.05),KchIP2 mRNA、Kv-LQT1 mRNA水平在右室中层心肌表达明显高于左室中层心肌(P<0.01或<0.05)。结论KchIP2、KvLQT1 mRNA水平在左右室中层心肌中表达上的差异可能是其离子流差异的分子基础。     

犬上腔静脉肌袖与右房心肌某些通道亚单位mRNA的表达

目的研究犬上腔静脉肌袖与右房游离壁快速激活延迟整流钾电流(IKr),L型钙电流(ICa-L),短暂外向钾电流(Ito)通道亚单位mRNA表达水平。方法8只健康杂种犬,取上腔静脉肌袖及右房游离壁,采用逆转录聚合酶链反应的方法测定IKrα亚单位ERG、ICa-Lα1亚单位CaV1.2、Itoα亚单位Kv4.3及β亚单位KChIP2mRNA表达水平并进行半定量分析。结果上腔静脉肌袖中ERG表达水平高于右房(P<0.05),而CaV1.2、Kv4.3、KChIP2的mRNA表达均低于右房(P<0.05)。结论上腔静脉肌袖与右房之间存在离子通道基因表达水平的差异。     

家兔界嵴组织电生理特征及意义

目的 研究界嵴组织电生理特征,探讨其在房性心律失常中的意义。方法 采用标准玻璃微电极技术,测量界嵴的横向和纵向传导速度。记录界嵴和梳状肌细胞跨膜动作电位(actionpotential,AP),以及异丙肾上腺素对他们的影响。结果 界嵴组织具有自发电活动。其纵向和横向传导速度分别为(58.04±5.47)、(13.26±3.07)cm/s,传导异向性(纵向/横向传导速度)为4.53±0.91。界嵴细胞AP时程较长,可见明显的平台期;梳状肌细胞平台期短,其AP形态类似三角形[APD20和APD90界嵴细胞为(28.1±3.5)、(145.3±7.1)ms,梳状肌细胞为(21.8±4.1)、(125.3±6.3)ms,P均<0.01]。正常台氏液灌流时,界嵴和梳状肌细胞无早期和晚期后除极。以4μmol/L异丙肾上腺素灌流后两者均可出现早期和晚期后除极,而且在界嵴上记录到短阵快速不规则电活动,并为0.1 mmol/L维拉帕米所终止。结论 界嵴组织具有自发电活动,在一定条件下可产生触发活动,它是心房内各向异性传导的典型。界嵴参与各种房性心律失常的发生和发展,可能与其电生理基础有关。     

阿魏酸钠对卵母细胞Kv1.2外向钾电流的影响

目的了解阿魏酸钠抗心律失常作用可能的分子机制。方法利用表达Kv1.2通道的卵母细胞为模型,以经典的Ⅲ类抗心律失常药物胺碘酮为对照,了解阿魏酸钠对Kv1.2通道的作用及其分子机制。结果阿魏酸钠和胺碘酮均能阻滞Kv1.2通道的外向钾电流,这一作用具有浓度依赖性。阿魏酸钠和胺碘酮对Kv1.2外向钾电流作用无差异(P>0.05)。结论阿魏酸钠对Kv1.2通道外向钾电流的阻滞作用可能是其抗心律失常作用的分子机制之一。     

界嵴的心内形态、电生理特性及其在心律失常中的作用

1　界嵴的形成及心内形态　　界嵴 (ｃｒｉｓｔａｔｅｒｍｉｎａｌｉｓ ,ＣＴ)位于右房侧壁 ,是自上腔静脉口前方至下腔静脉口前方的肌性隆起 ,与下腔静脉口前方的欧氏嵴 (ｅｕｓｔａｃｈｉａｎｖａｌｖｅ ,ＥＶ)相延续。　　当胚胎发育至第 6～ 8周时 ,静脉窦右角连同上、下腔静脉与原始心房融合 ,形成ＣＴ ,并将右房分成由原始静脉窦成分为主的光滑部和由原始心房部为主的小梁肌部。而处于原始起搏区域的起搏细胞也随着静脉窦移动而集中分布于右房上部及ＣＴ上部[1] 。　　ＣＴ的心内形态并非均匀一致。Ｋａｌｍａｎ等[2 ] 应用导管心内超…     

不同部位及不同方式心房起搏对心房激动的影响

目的 了解不同部位、不同方式心房起搏时P波、P－R间期以及心房激动顺序的特点，从而寻找最佳的心房单部位起搏方式。方法 对20例射频消融成功后的患者，分别放置高位右房、右心耳、Koch三角、希氏束以及冠状窦电极，若为左侧旁路则加置左心房电极，行不同部位、不同方式心房起搏。结果 Koch三角、Koch三角＋高位右房、左房、双房起膊时P波宽度、P－R间期无差异，但右心耳起搏时各导联P波增宽，P－R间期延长。从心房激动顺序分析，右心耳起搏时，激动传至希氏束区及冠状窦区的时间最长，而Koch三角、Koch三角＋高位右房及双房起搏时则较短，尤其是Koch三角、Koch三角＋高位右房起搏缩短更明显。另外，不同部位、不同方式起搏时右心房压力无差异。结论 Koch三角起搏在某种程度上可替代高位右房＋冠状窦起搏及双房起搏。     

自主神经系统对在体犬跨室壁复极不均一性影响的研究

目的　探讨自主神经系统对在体犬跨室壁复极离散度的影响。方法　用单相动作电位(MAP)记录技术 ,同步记录 12只开胸犬左心室游离壁心外膜心肌 (epicardium ,Epi)、中层心肌(midmyocardium ,Mid)和心内膜心肌 (endocardium ,Endo)的MAP。对自主神经刺激前和刺激过程中 ,三层心肌的跨室壁复极离散度和早期后除极的发生率进行比较。结果　起搏周长为 10 0 0ms时 ,在未刺激自主神经的情况下 ,Epi、Mid和Endo的单相动作电位时程 (MAPD)复极 90 %的时限 (MAPD90 )分别是 (2 78± 11)ms、(316± 16 )ms和 (2 70± 12 )ms;其中Mid的MAPD90 明显长于Epi和Endo的MAPD90 (P<0 0 1)。刺激交感神经时 ,Epi、Mid和Endo细胞的MAPD90 分别缩短 (19± 4 )ms、(45± 6 )ms、(18± 3)ms。与刺激前相比 ,跨室壁复极离散度由 (44± 4 )ms减少到 (15± 3)ms(P <0 0 1) ;但是交感神经刺激时 ,有 5只犬 (41% )的中层心肌出现了早期后除极。迷走神经刺激对三层心肌的MAPD90 值无明显影响。结论　 (1)在体犬心室肌存在跨室壁复极不均一性 ;(2 )交感神经刺激可减少跨室壁复极离散度 ,但易在Mid诱发早期后除极 ;(3)迷走神经刺激对跨室壁复极离散度无明显影响。     

天门冬氨酸对心室复极和室性心律失常的影响

目的研究腹腔注射天门冬氨酸(NMDA)对心室复极和室性心律失常诱发的影响。方法将36只成年Wistar大鼠随机分为对照组(CTL组)、NMDA组(N组)、NMDA+NMDA的受体拮抗剂MK-801组(N+M组),分别连续10d腹腔给予生理盐水、NMDA、NMDA+MK-801。记录体表心电图(II导联),并在Langerdorff灌流下行程控电刺激,记录左室前壁基底部(LAB)、前壁心尖部(LAA)、后壁基底部(LPB)和后壁心尖部(LPA)复极过程,测量单向动作电位时程(MAPD)和有效不应期(ERP),及其离散度,计算室性心律失常诱发率和频率阈值。结果与CTL组比较,N组PR间期、QT间期和QTc间期延长,心率增快;左室20%、复极三角和90%的复极时间(MAPD20、triangulation、MAPD90)延长,ERP/MAPD90较小;心室复极离散度增加[COVMAPD90:(0.153±0.017)vs(0.034±0.003),COVERP:(0.242±0.018)vs(0.078±0.009),P均0.01];室性心律失常诱发率增加(100%vs 16.7%,P均0.01)。而MK-801减弱了NMDA对心室复极和室性心律失常诱发的影响。结论慢性注射NMDA将延长心室复极时程,增加复极离散度和室性心律失常的易感性。     

犬右房最早激动点处心外膜双极电图特征研究

阐明犬右房心外膜双极电图特征,以助于局灶性心动过速射频消融时消融靶点的确定。采用自制9极梳状电极在犬右房界嵴中部三尖瓣环侧处起搏并同步记录双极心外膜电图。首先沿界嵴纵轴向上腔静脉方向放置梳状电极,记录心外膜双极电图,旋转梳状电极每隔30度记录心外膜双极电图,依次记录心外膜双极电图直到起始位置。结果:以起搏电极为圆心在4mm(M=4mm)范围内双极电图初始向量向下,呈“Q”型或“Qr”型。在距起搏电极10mm(M=10mm)处发生极性转化,呈“RS”型或“Rs”型。结论:双极电图特征可能有助于快速、精确确定局灶性心动过速的消融靶点。     

不同起搏部位对正常人体心肌复极离散的影响

目的 :观察正常人心脏不同部位或 2个部位同时起搏时的电生理及心室肌复极差异的变化。方法 :15例接受射频消融术后的患者 ,常规检查排除器质性心脏病。经冠状静脉窦将 1根标测电极送至左心室表面静脉分支 ,另 1根Pacing MAP电极送达右室心尖部 ,记录局部单向动作电位 (MAP)。分别起搏左心室心外膜、右心室心内膜及上述两部位同时起搏 ,行S1S1、S1S2 程序刺激。记录测量QRS波时限、QT间期、Tp Te 间期、MAP时程 (MAPD)等指标及心律失常事件。结果 :体表心电图上QT间期、Tp Te 间期在左室心外膜起搏 (376 .2 6ms、12 2 .5 9ms)、双心室起搏 (36 6 .4 2ms、12 4 .2 3ms)明显较右心室心内膜起搏 (349.33ms、10 4 .14ms)延长 (P <0 .0 1) ,伴有右室心尖部局部MAPD的相应变化。在相同总阵次的程序刺激中 ,左室心外膜起搏与双心室起搏时的室性心律失常多于右室心内膜起搏时 (P <0 .0 5 )。结论 :左室心外膜参与起搏后可能会增大心室肌的跨室壁复极差异 ,伴有复极时间的延长 ,从而使室性心律失常易于发生。     

Repolarization heterogeneity and rate dependency in a canine rapid pacing model of heart failure

Background

Repolarization heterogeneity and rate dependency have long been established as factors contributing to arrhythmogenic risk. However, there are conflicting observations regarding the nature and extent of ventricular repolarization heterogeneity that complicate understanding of arrhythmogenic mechanisms. To explore these disparate findings, we studied ventricular repolarization heterogeneity and rate dependency in a canine, rapid pacing model of heart failure.

Methods and Results

We studied ventricular repolarization heterogeneity and rate dependency in 10 canine hearts (5 normal and 5 after 1 month of rapid pacing at 240 beats per minute) by analyzing 64 body surface electrocardiograms, 64 epicardial, and 190 intramural plunge electrograms. We estimated mean ventricular depolarization and repolarization times from R- and T-wave peaks of the root-mean-square electrocardiogram (body surface) and local depolarization and repolarization times using activation-recovery interval (ARI) methods from recordings obtained during a range of fixed rate pacing. In addition, we estimated local epicardial and transmural gradients of ARIs to assess cardiac locations of greatest spatial repolarization heterogeneity. We compared changes in repolarization at different rates between normal and heart failure hearts. Findings documented prolongation of repolarization, repolarization rate dependency, and increased repolarization gradients in the heart failure hearts compared with control as observed from body surface, epicardial, and transmural measurements. Maximum local epicardial and intramural ARI gradients were comparable both in heart failure and control hearts. Intramural ARI distributions tended to be more irregular in the heart failure hearts compared with the systematic epicardium to endocardium ARI increase observed in control animals.

Conclusions

This study documented prolongation of repolarization, increase in both epicardial and transmural repolarization gradients, and irregularity of transmural distribution in a rapid pacing canine model of heart failure compared with control animals. The findings support previously published results of increased repolarization heterogeneity and repolarization prolongation observed in rapid pacing models of heart failure. New findings are the irregularity of transmural heterogeneity and the ability of noninvasive root-mean-square electrocardiogram R-T intervals to estimate mean ventricular repolarization duration in the setting of rapid pacing models of heart failure. These findings suggest increased arrhythmogenic risk in this model and potentially in patients with heart failure.     

风湿性心脏病慢性心房颤动患者界嵴连接蛋白40蛋白和基因转录表达

目的通过检测风湿性心脏病（风心病）慢性心房颤动（房颤）患者界嵴连接蛋白（connexin,Cx）40的蛋白表达、mRNA表达情况,探讨Cx40重构的形式与可能机制。方法选择风心病二尖瓣病变手术患者20例分为窦性心律（窦律）组10例,心房颤动（房颤）组10例,另取6例非风心病窦律患者作为对照组。换瓣术中剪取界嵴组织约200mg。采用Western blot蛋白印迹法检测Cx40蛋白表达量;实时荧光定量聚合酶链反应法检测Cx40mRNA表达水平。结果（1）风心病慢性房颤组界嵴Cx40蛋白表达水平明显较窦律组和对照组低。（2）3组患者界嵴Cx40mRNA表达量差异无统计学意义。结论风心病慢性房颤患者Cx40重构形式是Cx40表达下词;而Cx40重构的具体机制在于转录后水平。     

心房肌复极的电整复性与阵发性心房颤动发生机制的实验研究

目的 研究在体犬左、右心房肌的电整复性即动作电位时程整复性(APDR),观察其与阵发性心房颤动(房颤)发生的潜在机制.方法 使用单相动作电位技术记录14只犬左、右心房复极达90%的动作电位时程(APD_(90)),并通过S_1S_2程序刺激,观察APDR变化,即每一个舒张间期与刺激后发生心房肌复极APD_(90)的关系,并观察房颤的诱发情况.结果 APD_(90)左心房为(157.4±43.5)ms明显小于右心房(170.9±37.9)ms,P<0.05.心房肌在S_1S_2递减程序刺激下,左心房与右心房具有不同斜率的APDR曲线,左心房的APDR曲线斜率1.3±0.4大于右心房0.9±0.3,P<0.05.进行心房快速起搏S_1S_2刺激时,14只犬中共诱发出18阵房颤,其中左心房刺激发作12阵,明显多于右心房6阵(P<0.05).结论 左、右心房间具有单相动作电位时程的异质性及APDR不均一的复极特性,是诱发折返、发生和维持房颤的基质之一.     

Complete isolation of the pulmonary veins and posterior left atrium in chronic atrial fibrillation. Long-term clinical outcome

Aims: To evaluate the contribution of the posterior left atrium (LA)to chronic atrial fibrillation (AF). Methods and results: Twenty-seven patients with chronic-AF were studied. After pulmonaryvein (PV) isolation, the posterior-LA was isolated by ablationjoining the right- and left-PVs using an irrigated-tip catheter.Isolation was demonstrated by absent/dissociated posterior-LAactivity and the inability to pace the region. Ablation impactwas determined by the effect on cycle length (CL) and AF termination.Posterior-LA isolation was achieved using 35 ± 12 minof radiofrequency with total fluoroscopic and procedural durationsof 64 ± 16 and 199 ± 46 min, resulting in abolitionof electrograms (n = 21) or autonomous activity (n = 6; CL 820± 343 ms). AFCL increased from 156 ± 28 ms to162 ± 27 ms with PV-isolation and to 175 ± 32ms by posterior-LA exclusion (P < 0.0001). AF persisted inall after PV-isolation and terminated in 5 (19%) during posterior-LA-isolation.After 10 ± 6 months, 12 patients developed atrial tachycardia(four) or AF (eight); four underwent repeat posterior-LA-isolation,while the others required additional ablation/antiarrhythmics.After 21 ± 5 months, 17 (63%) were in sinus rhythm followingposterior-LA-isolation. Conclusion: This study demonstrates the feasibility of complete posterior-LAexclusion by catheter ablation. This strategy results in maintenanceof sinus rhythm in 63% at 2 years follow-up.     

Developmental evolution of the delayed rectifier current IKs in canine heart appears dependent on the β subunit minK

OBJECTIVES: We tested the hypothesis that the developmental changes occurring in I(Kr) and I(Ks) can be explained by changes in the expression of ERG encoding I(Kr), and KCNQ1, the beta subunit minK, and the recently reported subunit FHL2 encoding I(Ks). BACKGROUND: The delayed rectifier current contributes importantly to the developmental evolution of the canine myocardial action potential. Specifically, in left ventricular epicardial myocytes, I(Ks) is absent and I(Kr) is the major repolarizing current until age 4 weeks. With subsequent development, I(Ks) density increases and I(Kr) decreases, resulting in an altered voltage-time course of repolarization. METHODS: We used Western blotting and real-time polymerase chain reaction to compare the expression of ERG, KCNQ1, minK, and FHL2 in 1-week-old pups and adult dogs. RESULTS: ERG levels are high at 1 week and decrease significantly with age, consistent with developmental decrease in I(Kr). Whereas expression of KCNQ1 and FHL2 is unchanged between the two age groups, minK is minimally expressed at 1 week and increases in adults, consistent with developmental increase in I(Ks). CONCLUSIONS: A reduction in ERG explains the developmental decrease in I(Kr), whereas the accessory subunit minK appears to be the critical determinant of developmental evolution of I(Ks).     

犬冠状窦肌组织在左右心房间电传导中的作用

目的 探讨犬冠状窦肌组织在左右心房间电传导中的作用.方法 16只犬离体心脏在Langendorff灌流下通过冠状窦口电极、冠状窦远端电极和左房侧壁电极进行程控刺激,观察左右心房间电传导.结果 冠状窦口S1S1刺激可记录到冠状窦双电位,传至远端的时间为(44±21)ms,4例S1S2刺激使左房传导顺序改变.冠状窦远端S1S1刺激仅3例诱发电传导,传导时间为(41±15)ms,1例S1S2刺激使左房传导顺序改变.左房侧壁S1S1刺激电活动由冠状窦中部向两端传导.冠状窦口、冠状窦远端、左房侧壁S1S2刺激有效不应期分别为(122±19)ms、(114±12)ms(n=3)和(107±17)ms(P>0.05),进入有效不应期前左房侧壁刺激的电传导阻滞率为0,冠状窦口刺激电传导阻滞率为25%.结论 冠状窦内存在一条左右心房间的特殊的传导束,可能是一定条件下诱发并维持房性心律失常的心房间传导通路之一.     

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。