严重烫伤延长大鼠心室肌细胞动作电位时程的机制

严重烫伤引起心肌细胞动作电位时程（action potential duration,APD）延长,通过加重烫伤心肌细胞钙紊乱和诱发室性心律失常,促进烫伤心功能障碍的发生,但APD延长的机制尚不清楚。通过制作约40％体表面积（total body surface area,TBSA）Ⅲ度烫伤大鼠模型,在伤后12h大鼠心功能明显减弱时分离其心肌细胞,采用膜片钳技术观察心肌细胞APD以及动作电位复极化相关的重要离子通道电流,包括瞬间外向钾电流（transient outward K^＋ current,Ito）,L-型钙电流（L-type Ca^2＋ current,ICa-L）和内向整流钾电流（inward rectifier K^＋ current,IK1）。结果显示,烫伤后12h单个心肌细胞APD明显延长,APD50和APD90在烫伤组分别为（46．02±3．78）ms、（123．24±12．48）ms（n=19）,明显长于对照组的（23．28±4．85）ms、（72．12±3．57）ms（n=17）（P〈0．01）。烫伤引起,Ito电流密度降低,＋60 mV下烫伤组的电流密度（20．39±1．98）pA／pF（n=25）明显低于对照组的（34．15±3．78）pA／pF（n=20,P〈0．01）;烫伤组在-120至-80mV电压刺激下所产生的IK1电流密度显著低于对照组：而两组之间ICa-L电流密度、电压依赖性的激活和失活无显著性差异。结果提示,烫伤引起心肌细胞APD延长的机制与瞬间外向钾通道和内向整流钾通道功能下调有关。     

Calcineurin在心衰小鼠左心室跨壁电压依赖性钾电流下调中的作用

本文旨在探讨钙调神经磷酸酶(calcineurin,Ca N)在心衰心脏左室跨壁电压依赖性钾电流下调中的作用及意义。主动脉弓部分结扎法制备小鼠压力超负荷心衰模型,采用全细胞膜片钳技术,记录应用Ca N抑制剂环孢素A(cyclosporine A,Cs A)后,假手术或心衰小鼠心室肌内膜下(subendocardial,Endo)、外膜下(subepicardial,Epi)心肌细胞电压依赖性钾电流各种成分及动作电位(action potential,AP)的变化。结果显示:各组小鼠左室游离壁心肌细胞的Ca N活性存在明显区域性差异,Endo细胞Ca N活性均高于Epi。心衰时Endo、Epi细胞Ca N活性明显升高,而使用Cs A后Ca N活性降低。在心衰模型小鼠上,Cs A可部分逆转Ito密度的下调,完全逆转Endo和Epi细胞IK,slow密度的下调,完全逆转Endo细胞Iss密度的下调。Cs A可部分逆转心衰小鼠心室肌细胞动作电位时程(action potential duration,APD)的延长,使得增高了的AP跨壁复极离散度(transmural dispersion of repolarization,TDR)明显降低,Endo、Epi细胞APD90的比值由心衰时的4.8:1恢复到2.6:1。以上结果提示,心衰时Endo、Epi细胞Ca N不同程度的激活是电压依赖性钾电流非同步下调,AP的TDR增大的重要原因,抑制Ca N可望成为防治心衰心律失常和猝死的新策略。     

腺苷抗豚鼠室性心律失常的电生理研究

实验用全细胞膜片钳技术在单个豚鼠心室肌细胞上研究了腺苷 (Ado)对正常及异丙肾上腺素 (Iso)致豚鼠心室肌细胞动作电位、迟后除极 (DAD)、L 型钙电流 (ICa.L)和短暂内向电流 (Iti)的作用。结果表明 :(1)Ado在2 0～ 10 0 μmol/L时对豚鼠心室肌细胞动作电位和ICa .L无明显直接作用 ,但却可明显降低Iso所致的动作电位时程(APD)延长和ICa .L峰值增大 ,Iso (10nmol/L)使细胞APD50 从 3 40± 2 1ms延长到 486± 2 8ms (P <0 0 1) ,APD90从 3 61± 17ms延长至 5 0 1± 2 9ms (P <0 0 1) ;ICa .L峰值从 - 6 5 3± 1 4pA/pF增大到 - 18 2 8± 2 4pA/pF (P <0 0 1) ,电流电压曲线明显左移和下移 ;Ado (5 0 μmol/L)使APD50 和APD90 降至 40 3± 19ms和 419± 2 6ms ,但并不影响动作电位其它参数 ,使ICa.L峰值降低至 - 10 2± 1 5pA/pF (P <0 0 1)。 (2 )Iso (3 0nmol/L)可诱发心室肌细胞产生DADs,其发生率为 10 0 % ;Ado (5 0 μmol/L)可完全抑制Iso引发DADs;细胞经 - 40～ +2 0mV、时程 2s的除极电压 ,Iso (3 0nmol/L)诱导出Iti,其发生率为 10 0 % ;Ado (5 0 μmol/L)可明显抑制Iso致Iti的发生 ,其发生率降为 14 3 %。研究结果提示 ,Ado对豚鼠心室肌细胞动作电位和ICa.L无明显直接作用 ,但却可显著降低Is     

孕酮对豚鼠心室肌细胞动作电位的影响

目的：观察孕酮(pfogesterone)对心室肌细胞动作电位的影响。方法：采用玻璃微电极技术,引导离体豚鼠心室乳头肌细胞动作电位,观察孕酮不同浓度及作用时间对心室肌细胞动作电位及有效不应期的影响。结果：①较高浓度的孕酮使心室肌细胞动作电位零期最大除极速率(Vmax)和动作电位幅度(APA)降低,使心室肌细胞有效不应期(ERP)延长;②较高浓度孕酮使心室肌细胞动作电位时程APD20缩短;使动作电位时程APD90、APD延长。结论：孕酮具有抑制心室肌细胞Na^ 通道、K^ 通道和Ca^2 通道的作用。     

镉对大鼠心室肌细胞动作及L-型钙电流的影响

目的:探讨镉(Cd)对大鼠心室肌细胞动作电位(AP)及L-型钙电流(ICa-L)影响。方法:用常规微电极和全细胞膜片钳技术记录心肌细胞动作电位和ICa-L。结果:①不同浓度的CdCl2可降低大鼠心肌细胞动作电位幅值(APA),缩短复极化时程(APD)。②不同浓度的CdCl2明显抑制大鼠心室肌细胞钙通道电流。结论:CdCl2抑制大鼠心室肌细胞动作电位和ICa-L,可能是Cd对心肌毒性的重要机制之一。     

银杏苦内酯B对缺血豚鼠心室肌动作电位、L-型钙电流和延迟整流钾电流的作用

目的:研究银杏苦内酯B对正常和缺血心室肌细胞动作电位(action potential,AP),L-型钙电流(L-type calcium current,ICa-L)、延迟整流钾电流(Delayed Rectifier Currennt,IK)的影响.方法:用常规细胞内微电极方法记录豚鼠心室肌细胞动作电位,用全细胞膜片钳技术记录游离心室肌细胞离子流.结果:①在生理条件下,银杏苦内酯B可缩短心室肌细胞动作电位时程 (action potential duration,APD),但对AP其他参数无影响,银杏苦内酯B可增大IK,呈浓度依赖性,但对ICa-L无显著作用;②在缺血条件下,APD50、APD90明显缩短,RP、APA减小,Vmax减慢,而银杏苦内酯B则可延缓和减轻缺血所引起上述参数的变化;3.在缺血条件下,IK和ICa-L均受到抑制,但加入银杏苦内酯B后可逆转缺血所造成这两种离子流的减小.结论:银杏苦内酯B可对抗心肌缺血所引起的心肌电生理的变化,提示银杏苦内酯B可预防心律失常的发生.     

虎杖中白藜芦醇对豚鼠左心室流出道自律组织电活动的影响

目的:研究主要应用细胞内微电极技术研究白藜芦醇对豚鼠左心室流出道自律组织的电生理效应。方法:选取体重250～300g豚鼠,应用玻璃微电极技术记录动作电位并观察给药前后动作电位的变化。观察指标:最大舒张电位(MDP)、动作电位幅值(APA)、0相最大除极速度(Vmax)、4相自动除极速度(VDD)、复极至90%时间(APD90)和自发放电频率(RPF)。结果:白藜芦醇可抑制豚鼠左心室流出道自律细胞的电活动,显著降低左心室流出道自律细胞的APA、Vmax、VDD、RPF(P0.01);而对MDP和APD50及APD90无明显作用(30、60μmol/L)。结论:白藜芦醇可抑制左心室流出道自律细胞的电活动。     

抗心律失常药对豚鼠左心室流出道自律细胞电活动的影响

目的:研究抗心律失常药对豚鼠左心室流出道自律细胞电活动的影响。方法:采用标准玻璃微电极细胞内记录技术,记录并分析了四类抗心律失常药及腺苷对离体豚鼠左心室流出道自发慢反应电位的效应。结果:ⅠA类抗心律失常药1μmol/L奎尼丁可使左心室流出道自发慢反应电位的放电频率(RPF)和4相自动去极速度(VDD)减慢(P0.05),动作电位幅度(APA)降低(P0.05),0相最大去极速度(Vmax)减慢(P0.05),复极50%(APD50)和90%时间(APD90)延长(P0.05);ⅠB类抗心律失常药1μmol/L利多卡因灌流标本后,RPF和VDD减慢(P0.05),最大复极电位(MDP)绝对值和APA减小(P0.05),Vmax减慢(P0.05),APD50和APD90缩短(P0.05);ⅠC类抗心律失常药0.5μmol/L普罗帕酮可使RPF(P0.01)和VDD(P0.05)减慢,APA降低(P0.05),Vmax减慢(P0.01),APD50(P0.01)和APD90(P0.05)延长;Ⅱ类抗心律失常药5μmol/L普萘洛尔可使RPF和VDD减慢(P0.01),MDP绝对值和APA减小(P0.01),Vmax减慢(P0.05),APD50和APD90延长(P0.01);Ⅲ类抗心律失常药1μmol/L胺碘酮可使RPF和VDD减慢(P0.01),APA降低(P0.01),Vmax减慢(P0.05),APD50(P0.01)和APD90(P0.05)延长;Ⅳ类抗心律失常药1μmol/L维拉帕米可使RPF和VDD减慢(P0.01),MDP绝对值和APA减小(P0.05),Vmax减慢(P0.05),APD50和APD90延长(P0.05);50μmol/L腺苷可使RPF和VDD减慢(P0.05),APA降低(P0.05),Vmax减慢(P0.01),APD50和APD90缩短(P0.05)。结论:抗心律失常药均可显著降低左心室流出道组织的自律性,通过改变APD50和APD90影响有效不应期而起到抗心律失常作用。     

组胺致豚鼠心室乳头肌早发后去极化和触发活动的研究

采用微电极细胞内记录和电子计算机实时采样技术,研究了组胺致豚鼠心室乳头肌早发后去极化和触发活动。组胺(6.0μmol/L)可使动作电位APD_(50)、APD_(90)明显缩短(数据取自无异常自律性和振荡电位的细胞)。组胺可诱发早发后去极化(发生率57％),振荡电位和触发活动。早发后电位在低频驱动(0.2～1.0Hz)时易于发生且常常伴有动作电位时程的延长。触发活动可表现为快速自发性动作电位(发生率14％)。结果提示,组胺诱发的早发后去极化和触发活动可能和心性过敏反应等疾病发生的快速自律型心律失常有关。     

小剂量辣椒素对豚鼠心室肌细胞L-型钙电流的影响

应用全细胞膜片钳技术研究低浓度辣椒素(capsaicin,CAP)对单个豚鼠心室肌细胞L-型钙电流的影响及其作用机制.CAP(1～25 nmol/L)可浓度依赖性增加电压依赖性的ICa-L的峰值并下移I-V曲线.CAPl,10,25 nmol/L使ICa-L最大峰值分别由-9.67±0.7pA/pF增至-10.21±0.8pA/pF(P＞0.05),-11.37±0.8pA/pF和-12.84±0.9pA/pF(P＜0.05).CAP25nmol/L可明显使稳态激活曲线左移,激活中点电压(V0.5)由-20.76±2.0mV变至-26.71±3.0mV(P＜0.05),表明低浓度CAP改变了钙通道激活的电压依赖性.CAP25nmol/L对电压依赖性稳态失活曲线和ICa-L从失活状态下复活过程无明显影响.辣椒素受体(VR1)阻断剂钌红(RR,10μmol/L)可阻断低浓度辣椒素的效应.以上结果表明,低浓度辣椒素使钙通道稳态激活曲线左移,增加ICa-L,这一效应可能由VRl介导.     

Altered spatial calcium regulation enhances electrical heterogeneity in the failing canine left ventricle: implications for electrical instability

Myocytes across the left ventricular (LV) wall of the mammalian heart are known to exhibit heterogeneity of electrophysiological properties; however, the transmural variation of cellular electrophysiology and Ca(2+) homeostasis in the failing LV is incompletely understood. We studied action potentials (APs), the L-type calcium (Ca(2+)) current (I(Ca,L)), and intracellular Ca(2+) transients ([Ca(2+)](i)) of subendocardial (Endo), midmyocardial (Mid), and subepicardial (Epi) tissue layers in the canine normal and tachycardia pacing-induced failing left ventricles. Heart failure (HF) was associated with significant prolongation of the AP duration in Mid myocytes. There were no differences in I(Ca,L) density in normal Endo, Mid, and Epi myocytes, whereas in the failing heart, I(Ca,L) density was downregulated by 45% and 26% (at +10 mV) in Endo and Mid myocytes, respectively. The rates of sarcoplasmic reticulum (SR) Ca(2+) release and decay of the [Ca(2+)](i) were slowed, and the amplitude of the [Ca(2+)](i) was depressed in Endo and Epi myocytes isolated from failing, compared with normal, hearts. Experiments in sodium (Na(+))-free solutions showed that Epi and Mid myocytes of the failing ventricle exhibit a greater reliance on the Na(+)-Ca(2+) exchanger to remove cytosolic Ca(2+) than myocytes isolated from normal hearts. Simulation studies in Endo, Mid, and Epi canine myocytes demonstrate the importance of L-type current density and SR Ca(2+) uptake in modulating the potentially arrhythmogenic repolarization in HF. In conclusion, these results demonstrate that spatially heterogeneous decreases in I(Ca,L) and defective cytosolic Ca(2+) removal contribute to the altered [Ca(2+)](i) and AP profiles across the canine failing LV. These distinct electrophysiological features in myocytes from a failing heart contribute to a characteristic electrogram arising from increased dispersion of refractoriness across the LV, which may result in significant arrhythmogenic sequellae.     

Altered connexin43 expression produces arrhythmia substrate in heart failure

Recently, we found that repolarization heterogeneities between subepicardial and midmyocardial cells can form a substrate for reentrant ventricular arrhythmias in failing myocardium. We hypothesized that the mechanism responsible for maintaining transmural action potential duration heterogeneities in heart failure is related to intercellular uncoupling from downregulation of cardiac gap junction protein connexin43 (Cx43). With the use of the canine model of pacing-induced heart failure, left ventricles were sectioned to expose the transmural surface (n = 5). To determine whether heterogeneous Cx43 expression influenced electrophysiological function, high-resolution transmural optical mapping of the arterially perfused canine wedge preparation was used to measure conduction velocity (theta(TM)), effective transmural space constant (lambda(TM)), and transmural gradients of action potential duration (APD). Absolute Cx43 expression in failing myocardium, quantified by confocal immunofluorescence, was uniformly reduced (by 40 +/- 3%, P < 0.01) compared with control. Relative Cx43 expression was heterogeneously distributed and lower (by 32 +/- 18%, P < 0.05) in the subepicardium compared with deeper layers. Reduced Cx43 expression in heart failure was associated with significant reductions in intercellular coupling between transmural muscle layers, as evidenced by reduced theta(TM) (by 18.9 +/- 4.9%) and lambda(TM) (by 17.2 +/- 1.4%; P < 0.01) compared with control. Heterogeneous transmural distribution of Cx43 in failing myocardium was associated with lower subepicardial theta(TM) (by 12 +/- 10%) and lambda(TM) (by 13 +/- 7%), compared with deeper transmural layers (P < 0.05). APD dispersion was greatest in failing myocardium, and the largest transmural APD gradients were consistently found in regions exhibiting lowest relative Cx43 expression. These data demonstrate that reduced Cx43 expression produces uncoupling between transmural muscle layers leading to slowed conduction and marked dispersion of repolarization between epicardial and deeper myocardial layers. Therefore, Cx43 expression patterns can potentially contribute to an arrhythmic substrate in failing myocardium.     

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I(to) K(+) currents,and [Ca(2+)](i) transients

Transient outward K(+) current density (I(to)) has been shown to vary between different regions of the normal myocardium and to be reduced in heart disease. In this study, we measured regional changes in action potential duration (APD), I(to), and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients of ventricular myocytes derived from the right ventricular free wall (RVW) and interventricular septum (SEP) 8 wk after myocardial infarction (MI). At +40 mV, I(to) density in sham-operated hearts was significantly higher (P < 0.01) in the RVW (15.0 +/- 0.8 pA/pF, n = 47) compared with the SEP (7.0 +/- 1.1 pA/pF, n = 18). After MI, I(to) density was not reduced in SEP myocytes but was reduced (P < 0.01) in RVW myocytes (8.7 +/- 1.0 pA/pF, n = 26) to levels indistinguishable from post-MI SEP myocytes. These changes in I(to) density correlated with Kv4.2 (but not Kv4.3) protein expression. By contrast, Kv1.4 expression was significantly higher in the RVW compared with the SEP and increased significantly after MI in RVW. APD measured at 50% or 90% repolarization was prolonged, whereas peak [Ca(2+)](i) transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [Ca(2+)](i) transients were eliminated by MI. Our results demonstrate that the significant regional differences in I(to) density, APD, and [Ca(2+)](i) between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI.     

兔心室肌细胞电生理异质性研究--缺血对动作电位和钾流的影响

实验用全细胞膜片箝技术,观察正常及缺血条件下,兔心内膜下心室肌细胞与心外膜下心室肌细胞的动作电位和稳态外向钾流及其变化。结果显示：（１）正常条件下,心外膜下心室肌细胞与心内膜下心室肌细胞动作电位形态有差异,心外膜下心室肌细胞动作电位时程（ＡＰＤ）较短,复极１期后有明显的初迹,动作电位形态是“锋和圆顶”,而心内膜下心室肌细胞ＡＰＤ较长,并且没有上述动作电位形态特征。这两类细胞静息电位无差异。（２）在     

Ca2+/calmodulin-dependent protein kinase II-dependent remodeling of Ca2+ current in pressure overload heart failure

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity is increased in heart failure (HF), a syndrome characterized by markedly increased risk of arrhythmia. Activation of CaMKII increases peak L-type Ca(2+) current (I(Ca)) and slows I(Ca) inactivation. Whether these events are linked mechanistically is unknown. I(Ca) was recorded in acutely dissociated subepicardial and subendocardial murine left ventricular (LV) myocytes using the whole cell patch clamp method. Pressure overload heart failure was induced by surgical constriction of the thoracic aorta. I(Ca) density was significantly larger in subepicardial myocytes than in subendocardial/myocytes. Similar patterns were observed in the cell surface expression of alpha1c, the channel pore-forming subunit. In failing LV, I(Ca) density was increased proportionately in both cell types, and the time course of I(Ca) inactivation was slowed. This typical pattern of changes suggested a role of CaMKII. Consistent with this, measurements of CaMKII activity revealed a 2-3-fold increase (p < 0.05) in failing LV. To test for a causal link, we measured frequency-dependent I(Ca) facilitation. In HF myocytes, this CaMKII-dependent process could not be induced, suggesting already maximal activation. Internal application of active CaMKII in failing myocytes did not elicit changes in I(Ca). Finally, CaMKII inhibition by internal diffusion of a specific peptide inhibitor reduced I(Ca) density and inactivation time course to similar levels in control and HF myocytes. I(Ca) density manifests a significant transmural gradient, and this gradient is preserved in heart failure. Activation of CaMKII, a known pro-arrhythmic molecule, is a major contributor to I(Ca) remodeling in load-induced heart failure.     

Action potential characterization in intact mouse heart: steady-state cycle length dependence and electrical restitution

Transgenic mice have been increasingly utilized to investigate the molecular mechanisms of cardiac arrhythmias, yet the rate dependence of the murine action potential duration and the electrical restitution curve (ERC) remain undefined. In the present study, 21 isolated, Langendorff-perfused, and atrioventricular node-ablated mouse hearts were studied. Left ventricular and left atrial action potentials were recorded using a validated miniaturized monophasic action potential probe. Murine action potentials (AP) were measured at 30, 50, 70, and 90% repolarization (APD(30)-APD(90)) during steady-state pacing and varied coupling intervals to determine ERCs. Murine APD showed rate adaptation as well as restitution properties. The ERC time course differed dramatically between early and late repolarization: APD(30) shortened with increasing S1-S2 intervals, whereas APD(90) was prolonged. When fitted with a monoexponential function, APD(30) reached plateau values significantly faster than APD(90) (tau = 29 +/- 2 vs. 78 +/- 6 ms, P < 0.01, n = 12). The slope of early APD(90) restitution was significantly <1 (0.16 +/- 0.02). Atrial myocardium had shorter final repolarization and significantly faster ERCs that were shifted leftward compared with ventricular myocardium. Recovery kinetics of intracellular Ca(2+) transients recorded from isolated ventricular myocytes at 37 degrees C (tau = 93 +/- 4 ms, n = 18) resembled the APD(90) ERC kinetics. We conclude that mouse myocardium shows AP cycle length dependence and electrical restitution properties that are surprisingly similar to those of larger mammals and humans.     

Modeling ventricular repolarization: effects of transmural and apex-to-base heterogeneities in action potential durations

Heterogeneities in the densities of membrane ionic currents of myocytes cause regional variations in action potential duration (APD) at various intramural depths and along the apico-basal and circumferential directions in the left ventricle. This work extends our previous study of cartesian slabs to ventricular walls shaped as an ellipsoidal volume and including both transmural and apex-to-base APD heterogeneities. Our 3D simulation study investigates the combined effect on repolarization sequences and APD distributions of: (a) the intrinsic APD heterogeneity across the wall and along the apex-to-base direction, and (b) the electrotonic currents that modulate the APDs when myocytes are embedded in a ventricular wall with fiber rotation and orthotropic anisotropy. Our findings show that: (i) the transmural and apex-to-base heterogeneities have only a weak influence on the repolarization patterns on myocardial layers parallel to the epicardium; (ii) the patterns of APD distribution on the epicardial surface are mostly affected by the apex-to-base heterogeneities and do not reveal the APD transmural heterogeneity; (iii) the transmural heterogeneity is clearly discernible in both repolarization and APD patterns only on transmural sections; (iv) the apex-to-base heterogeneity is clearly discernible only in APD patterns on layers parallel to the epicardium. Thus, in our orthotropic ellipsoidal wall, the complex 3D electrotonic modulation of APDs does not fully mix the effects of the transmural and apex-to-base heterogeneity. The intrinsic spatial heterogeneity of the APDs is unmasked in the modulated APD patterns only in the appropriate transmural or intramural sections. These findings are independent of the stimulus location (epicardial, endocardial) and of Purkinje involvement.     

Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents

Gap junction redistribution and reduced expression, a phenomenon termed gap junction remodeling (GJR), is often seen in diseased hearts and may predispose toward arrhythmias. We have recently shown that short-term pacing in the mouse is associated with changes in connexin43 (Cx43) expression and localization but not with increased inducibility into sustained arrhythmias. We hypothesized that short-term pacing, if imposed on murine hearts with decreased Cx43 abundance, could serve as a model for evaluating the electrophysiological effects of GJR. We paced wild-type (normal Cx43 abundance) and heterozygous Cx43 knockout (Cx43+/-; 66% mean reduction in Cx43) mice for 6 h at 10-15% above their average sinus rate. We investigated the electrophysiological effects of pacing on the whole animal using programmed electrical stimulation and in isolated ventricular myocytes with patch-clamp studies. Cx43+/- myocytes had significantly shorter action potential durations (APD) and increased steady-state (Iss) and inward rectifier (I(K1)) potassium currents compared with those of wild-type littermate cells. In Cx43+/- hearts, pacing resulted in a significant prolongation of ventricular effective refractory period and APD and significant diminution of Iss compared with unpaced Cx43+/- hearts. However, these changes were not seen in paced wild-type mice. These data suggest that Cx43 abundance plays a critical role in regulating currents involved in myocardial repolarization and their response to pacing. Our study may aid in understanding how dyssynchronous activation of diseased, Cx43-deficient myocardial tissue can lead to electrophysiological changes, which may contribute to the worsened prognosis often associated with pacing in the failing heart.     

Effects of ectopic pacing on repolarization of the chicken left ventricle

Effects of ectopic pacing on left ventricular repolarization were studied in six anesthetized open-chest chickens. In each animal, unipolar electrograms were acquired from as many as 98 sites with 14 plunge needles (seven transmural locations between epicardium and endocardium in each needle). Activation-recovery intervals (ARIs), corrected to the cycle length, were used for estimating repolarization. At baseline, the nonuniform ARI distribution in the left ventricle resulted in the apicobasal differences being greater than the transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing resulted in decreasing the transmural repolarization gradient and increasing the differences in the apex-to-base direction. The basal, but not apical transmural differences contributed to the total left ventricular transmural gradient. The total left ventricular apicobasal gradient was contributed by the apicobasal differences in mid-myocardial and subendocardial layers more than in subepicardial ones. Thus, in in situ chicken hearts, the transmural and apicobasal ARI gradients exist within the left ventricle with the shortest ARIs in the basal subepicardium and the longest ARIs in the subendocardium of the apical and middle parts of the left ventricle. Apicobasal compared to transmural heterogeneity of local repolarization properties contributes more to the total left ventricular repolarization gradient.