心房颤动患者瞬间外向钾电流重构的分子基础

目的 研究心房颤动（AF）患者瞬间外向钾电流（Itol)重构的分子基础。方法 应用RT－PCR、免疫组化和免疫电镜方法检测持续窦性心律（SR）、阵发性AF（PAF）、慢性AF小于或等于6个月（AF≤6M）和大于6个月（AF＞6M）组患者右心耳组织电压依赖kv4.3钾通道α亚基（VDkv4.3α）基因和蛋白表达，并以图像分析系统对组化抗原表达进行半定量分析。结果 PAF、AF≤6M和＞6M组kv4.3αmRNA的表达明显低于SR组。kv4.3α mRNA表达与AF分数、左心房内径及平均心房率成明显负相关，经ANOVA剔除左心房内径的影响，各组mRNA表达较SR组仍显著下降（P＜0．05）。离子通道阳性表达为棕褐色的细颗粒状，主要分布在细胞膜和胞浆内的T管系统；免疫电镜检测，VDkv4.3α特异的阳性表达为电子密度高的黑色圆形胶体金颗粒，在细胞膜呈现不连续的点状分布，在胞浆T管内呈点状散在分布。组化结果半定量分析表明，PAF、AF≤6M和AF＞6M组中kv4.3α蛋白表达较SR组均明显下降，kv4.3α蛋白的表达与临床资料进行直线回归分析，发现kv4.3α蛋白表达较SR组均明显下降，kv4.3α蛋白的表达与临床资料进行直线回归分析，发现kv4.3α的蛋白表达仅与AF分数呈明显负相关；并且5例风湿性心脏病患者左、右心耳VDkv4.3α蛋白表达差别不明显。结论 VDkv4.3α钾通道除分布在细胞膜外，广泛分布在胞浆的T管系统。慢性AF伴发VDkv4.3α基因和蛋白表达同步下调，提示心房肌细胞VDkv4.3钾通道密度下调，可能是慢性AF患者Itol下降的分子基础。     

房颤犬心房间质重塑的相关细胞因子表达

目的研究房颤与心房结构重构的关系以及心房结构重构对心脏间质细胞调控相关的TGFB1,FGFR一1,VEGF等相关细胞因子表达的影响。方法实验动物随机分为三组：房颤式起搏组、T型钙通道阻滞剂组、正常对照组,24周后取其心房组织进行免疫组化染色,然后使用图像软件测量并比较I型胶原和TGFβ,FGFR—l,VEGF的表达量;分析3组犬心房调控因子与I型胶原蛋白表达量的相关性。结果房颤式起搏组的I型胶原表达量明显高于T型钙通道阻滞剂组和正常对照组。房颤式起搏组和正常对照组的心房组织TGF131表达与I型胶原有统计学相关性,而T型钙通道阻滞剂组无统计学相关性;三组心房组织的FGFR一1、VEGF表达量与I型胶原均无统计学相关性。结论持续性房颤可能导致心房发生明显的结构重塑,TGFβ1能具有很强的致心房纤维化作用。     

胺碘酮对特发性房颤心房重构逆转作用观察

目的 :探讨胺碘酮对特发性房颤的治疗及对逆转心房心肌重构的作用。方法 :选择 1998- 0 6～ 2 0 0 0 - 0 7住院的特发性房颤患者 （除外房颤持续时间小于 6月和阵发性房颤间隔小于 1月 ,每次持续时间少于 48h者 ） 94例。随机分为胺碘酮治疗组 32例 ,普罗帕酮治疗组 32例及安慰剂组 30例。治疗前后行心电图、心脏超声、肝、肾功及甲状腺功能检查。出院后嘱患者 1,3,6 ,12月复查上述项目 1次。结果 :胺碘酮与普罗帕酮治疗组 ,均可使特发性房颤复律 ,但胺碘酮组较普罗帕酮组复律时间稍长 （约 1周 ） ,维持窦性心律的作用中 ,胺碘酮优于普罗帕酮组 ,12月后转复成功率分别为 81%和 5 6 % ,与安慰剂组自动复律 2 0 % （6 / 30 ）比较有显著差异 （P<0 .0 1）。随访 1,3,6 ,12月胺碘酮组左心房直径缩小 ,左心室舒张早期经二尖瓣血流的最高值 （E峰值 ）和左心房收缩时经二尖瓣血流的最大值 （A峰值 ）、E/ A增大。1,3,6 ,12月间比较有显著性差异 （P<0 .0 1） ,普罗帕酮组上述指标有所改善 ,但差异不显著 （P>0 .0 5 ） ,安慰剂组则无变化。结论 :胺碘酮对特发性房颤复律及对逆转心房心肌重构安全有效     

心房颤动患者心房组织延迟整流钾通道基因表达的研究

目的 探讨心房颤动（AF）患者心房组织延迟整流钾通道（Kv1、5、HERG、KvLQT1通道）基因表达的变化。方法 以窦性心律组（SR组）为对照，应用逆转录-聚合酶链反应（RT—PCR），以三磷酸甘油醛脱氢酶（GAPDH）为内参照，检测35例风湿性心脏瓣膜病患者右心耳组织Kv1．5、HERG、KvLQT1通道的mRNA表达量。结果 和SR组相比，Kv1．5钾通道mRNA表达在慢性房颤组（CAF组）下降显著，有统计学意义（P〈0．05），在阵发性房颤组（PAF组）差异无统计学意义（P〉0．05）；HERG钾通道和KvLQT1钾通道mRNA表达CAF组和PAF组差异均无统计学意义（P〉0．05）。结论 Kv1．5钾通道转录水平下调可能是相应超速延迟整流钾电流（IKur）重构的分子基础，其基因表达异常是AF电重构的重要环节；HERG钾通道和KvLQT1钾通道在基因转录水平差异无统计学意义，与AF模型快速延迟整流钾电流（IKr）和缓慢延迟整流钾电流（IKs）无变化相符。     

黏着斑激酶介导信号通路在房颤模型小鼠心房重构中的研究 张培德，李飞，芮璐，王巍

目的 观察房颤小鼠模型心房重构改变,以及探索黏着斑激酶（FAK）及其介导下游信号通路AKT/S6K在心房重构中分子改变。 方法 利用为心脏特异性表达人源肾素原受体 (pRR) 的转基因小鼠作为房颤小鼠模型,选取野生型C57BL/6J小鼠为对照组,本研究两组各选取16例8月龄小鼠作为研究对象,通过超声检测观察心房心室改变;获取心房组织,分别进行Masson病理染色和蛋白免疫印迹,观察两组纤维化程度以及FAK及其下游通路在两组小鼠心房组织中的变化。 结果 房颤模型小鼠在8月龄已经出现明显的持续性房颤,心脏超声提示房颤组小鼠心房和心室都较对照组小鼠扩大,有心房重构,病理提示房颤组小鼠心房纤维化程度较高,同时FAK及下游AKT/S6K通路蛋白的磷酸化表达均发生上调。 结论 心房重构是心房颤动引起的心肌组织结构的变化,为房颤持续和血栓形成提供基质。房颤可引起心房扩大和纤维化形成,其中FAK介导的AKT/SK通路可能是参与重构的重要分子。     

Endocannabinoids and cannabinoid analogues block human cardiac Kv4.3 channels in a receptor-independent manner

Endocannabinoids are amides and esters of long chain fatty acids that can modulate ion channels through both receptor-dependent and receptor-independent effects. Nowadays, their effects on cardiac K⁺ channels are unknown even when they can be synthesized within the heart. We have analyzed the direct effects of endocannabinoids, such as anandamide (AEA), 2-arachidonoylglycerol (2-AG), the endogenous lipid lysophosphatidylinositol, and cannabinoid analogues such as palmitoylethanolamide (PEA), and oleoylethanolamide, as well as the fatty acids from which they are endogenously synthesized, on human cardiac Kv4.3 channels, which generate the transient outward K⁺ current (I_to1). Currents were recorded in Chinese hamster ovary cells, which do not express cannabinoid receptors, by using the whole-cell patch-clamp. All these compounds inhibited I_Kv4.3 in a concentration-dependent manner, AEA and 2-AG being the most potent (IC₅₀ ∼ 0.3-0.4 µM), while PEA was the least potent. The potency of block increased as the complexity and the number of C atoms in the fatty acyl chain increased. The effects were not mediated by modifications in the lipid order and microviscosity of the membrane and were independent of the presence of MiRP2 or DPP6 subunits in the channel complex. Indeed, effects produced by AEA were reproduced in human atrial I_to1 recorded in isolated myocytes. Moreover, AEA effects were exclusively apparent when it was applied to the external surface of the cell membrane. These results indicate that at low micromolar concentrations the endocannabinoids AEA and 2-AG directly block human cardiac Kv4.3 channels, which represent a novel molecular target for these compounds.     

心房颤动患者高敏C反应蛋白的变化及与心房重构的关系

目的:探讨心房颤动(房颤)患者血清高敏C反应蛋白(hs-CRP)的变化,及与左房内径(LAD)的相关性。方法:选取房颤患者120例(持续性房颤组56例,阵发性房颤组64例),窦性心律者60例为对照组,采用超声心动图测量2组的LAD,免疫速率散射比浊法测定hs-CRP含量,并对结果进行相关分析。结果:持续性房颤组血清hs-CRP的水平显著高于阵发性房颤组和对照组,差异有统计学意义。而阵发性房颤组患者血清hs-CRP水平虽高于对照组,但差异无统计学意义。房颤组患者血清hs-CRP水平与LAD存在正相关关系。结论:持续性房颤患者hs-CRP增高,与LAD呈正相关。     

冷冻球囊消融与射频消融对阵发性心房颤动患者心房重构的影响

目的:比较冷冻球囊消融(CBA)与射频消融(RFA)对阵发性心房颤动(房颤)患者心房重构的影响.方法:本研究选取在2014年5月-2017年5月于郑州大学第一附属医院因阵发性房颤行CBA或RFA治疗的患者.所有患者均于术前、术后半年、1年、2年和3年时行12导联心电图或24 h动态心电图和超声心动图检查.左心房电重构通...     

Different patterns of atrial remodeling after catheter ablation of chronic atrial fibrillation

Atrial Substrate Remodeling After Chronic AF Ablation . Background: Multiple remodeling patterns have been observed after catheter ablation of atrial fibrillation (AF). Objective: We aimed to clarify the electrical/structural properties associated with recurrences after ablation of chronic AF. Methods: After a stepwise ablation procedure in 120 consecutive patients with persistent/long‐lasting persistent AF, 36 had a recurrence of AF (Group 1/Group 2: recurrence with paroxysmal/persistent AF, n = 16/20). Results: During the first procedure, the left atrial (LA) bipolar voltage did not differ between the 2 groups, and the LA volume was smaller in Group 1 than in Group 2 and it was the only factor predicting the recurrent types (P = 0.009, OR = 1.04). In the second procedure, the bipolar voltage of the global left atrium increased (1.33 ± 0.11 mV vs 1.76 ± 0.16 mV, P = 0.001) in Group 1 and decreased (1.31 ± 0.14 mV vs 0.90 ± 0.12 mV, P = 0.01) in Group 2, when compared with that of the first procedure. The LA low‐voltage area (<0.5 mV) decreased in Group 1, and increased in Group 2. The LA volume (90 ± 8 cm³ vs 72 ± 8 cm³, P = 0.002) decreased in the second procedure in Group 1. It remained the same in Group 2. The right atrial substrates did not change between the procedures. After a follow‐up of 27 ± 3 months, all patients in Group 1 and 14 patients in Group 2 remained in sinus rhythm (P = 0.02). Conclusion: A better outcome with reverse electrical and structural remodeling occurred after the ablation of chronic AF when the recurrence was paroxysmal AF. Progressive electrical remodeling without any structural remodeling developed in those with a recurrence involving persistent AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 385‐393)     

The effect of left atrial remodeling after cryoballoon ablation and radiofrequency ablation for paroxysmal atrial fibrillation

BackgroundCryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the most common procedures used to treat refractory atrial fibrillation (AF) and are performed through pulmonary vein isolation (PVI). Studies have shown that CBA can approximately match the therapeutic effects of RFA against AF. However, few studies have investigated the difference between CBA and RFA of the effects on left atrial remodeling for paroxysmal AF.ObjectiveAtrial remodeling is considered pivotal to the occurrence and development of AF, therefore we sought to assess the influence of atrial remodeling in patients with paroxysmal AF after CBA and RFA in this study.MethodsIn this nonrandomized retrospective observational study, we enrolled 328 consecutive patients who underwent CBA or RFA for refractory paroxysmal AF in May 2014 to May 2017 in our hospital. After propensity score matching, 96 patients were included in the CBA group, and 96 were included in the RFA group. Patients were asked to undergo a 12‐lead electrocardiogram, a 24‐h Holter monitor, and an echocardiogram and to provide their clinical history and symptoms at 6 months and 1, 2, and 3 years postprocedurally. Electrical remodeling of the left atrium was assessed by P wave dispersion (Pdis); structural remodeling was assessed by the left atrium diameter (LAD) and left atrial volume index (LAVI) during scheduled visits.ResultsAs of January 2020, compared with baseline, at 1 year, 2 years, and 3 years after ablation, the average changes in Pdis (∆Pdis), LAD (∆LAD), and LAVI (∆LAVI) were significant in both the CBA and RFA groups. Six months after ablation, ∆Pdis, ∆LAD, and ∆LAVI were greater in the CBA group than in the RFA group. There was no significant difference between the two groups in AF/flutter recurrence, but the AF/flutter‐free survival time of CBA group may be longer than RFA group after 2 years after ablation. A higher ∆Pdis, ∆LAD, or ∆LAVI at 1 year after ablation may increase AF/flutter‐free survival.ConclusionsAlthough CBA and RFA are both effective in left atrial electrical and structural reverse‐remodeling in paroxysmal AF, CBA may outperform RFA for both purposes 6 months after ablation. However, during long‐term follow‐up, there was no significant intergroup difference.     

慢性心房颤动患者消融术后左心房和左心室结构远期变化

目的观察维持窦性心律(窦律)对慢性心房颤动(房颤)射频消融术后患者左心房和左心室结构的影响。方法入选38例慢性房颤行射频消融术的患者,分别于术前、术后1年行超声心动图检查,测量的超声心动图指标为左心房前后径、左心房上下径、左心房左右径、左心房最大容积、左心室舒张末内径、左心室收缩末内径,左心室射血分数,评估房颤有无复发对左心房及左心室重构的影响。结果 31例慢性房颤患者完成随访,随访时间为(13.45±1.46)个月,将其按消融效果分为复发组(15例)和非复发组(16例)。随访结果如下:(1)消融术前复发组与非复发组超声指标的基线资料比较,差异无统计学意义(P0.05)。(2)复发组术后12个月左心房前后径、左心房上下径、左心房左右径、左心房最大容积、左心室舒张末内径、左心室收缩末内径、左心室射血分数与术前比较,差异无统计学意义(P0.05);(3)非复发组消融术后12个月左心房前后径较术前减小[(38.73±3.77)mmvs.(41.86±4.73)mm,P0.01],左心房上下径较术前减小[(58.03±4.31)mmvs.(61.70±3.80)mm,P0.01],左心房左右径较术前减小[(43.93±6.06)mmvs.(46.08±6.62)mm,P0.01],左心房最大容积较术前减小[(75.78±22.27)mLvs.(83.18±24.29)mL,P0.01],左心室舒张末内径较术前减小[(45.85±4.98)mmvs.(48.26±5.36)mm,P0.01]、左心室收缩末内径较术前减小[(28.74±4.27)mmvs.(31.44±5.32)mm,P0.01],左心室射血分数较术前增加[68.03%±4.58%vs.62.75%±7.23%,P0.01],差异有统计学意义。结论维持窦律能使射频消融术后12个月的慢性房颤患者左心房及左心室逆向重构,左心室收缩功能改善。     

心房颤动患者离子重构的分子基础

目的　研究心房颤动 (AF)患者离子重构的分子基础。方法　以先天性心脏病 (CHD)和风湿性心脏病 (RHD)持续窦性心律 (SR)患者为对照 ,应用半定量RT PCR法检测RHD伴阵发性AF(PAF)慢性AF 6个月 (AF 6M )和慢性AF >6个月 (AF >6M )患者心房肌L 型电压依赖钙通道α1c亚基 (LVDCCα1c)、电压依赖KV4 3钾通道α亚基 (VDKV4 3α)和电压依赖钠通道α亚基 (VDSCα)mRNA的表达。结果　SR组内CHD患者与RHD患者LVDCCα1c、VDKV4 3α和VDSCα的mRNA表达差别无明显性 ;与对照组相比 ,各组AF患者VDSCα的表达没有改变 ;LVDCCα1c在AF >6M患者中的表达显著下降 ,而在PAF和AF 6M患者中的表达有不同程度下调 ,但无统计学意义 ;LVDCCα1cmRNA表达与心房率、左、右心房内径成明显负相关 ,并且其表达随AF分数增高逐渐下降 ;单因素协方差分析 (ANOVA)矫正心房内径的影响 ,AF >6M患者α1cmRNA表达仍明显下降 (P <0 0 1)。KV4 3αmRNA在PAF、AF 6M和AF >6M患者中的表达均显著降低。KV4 3钾通道α亚单位mRNA表达与AF分数、左心房内径和平均心房率均成明显负相关 ,经ANOVA剔除左心房内径的影响 ,各组mRNA表达较SR组仍显著下降 (P <0 0 5 )。结论　L 型钙通道和KV4 3钾通道转录水平下调是相应ICaL和Ito1重构的分子基础 ,基因表     

Reverse dedifferentiation of atrial cardiomyocytes after restoration of sinus rhythm from atrial fibrillation in goats

Objective Chronic atrial fibrillation （AF） results in dedifferentiation of atrial cardiomyocytes that plays an important role in the perpetuation of AF. In this study, we aimed to investigate the changes oftitin and a-smooth muscle actin （α-SMA） after long time of AF reversal. Methods Twenty-four goats were randomized into four groups： （1） sinus rhythm （SR）, （2） 3 months AF （3-too AF）, （3） 3 months SR after 3 months AF （3-mo post AF）, （4） 6 months SR after 3-mo AF （6-mo post AF）, with 6 in each group. By pacing on the anterior bottom of left atria appendage （LAA）, we established a goat model of chronic AF. Atria effective refractory period （AERP） was measured with electrophysiological methods. Ultra-structure was studied with echocardiography, light and electron microscopy. Titin and α-SMA protein expressions were determined by Western blot. Results The animals underwent high rate pacing on LAA for a mean of 42.23± 21.70 days before presenting AF. Electrophysiological analysis revealed that AERP completely resumed in 3-mo post AF goats. Echocardiography displayed that the size of left atrium resumed almost in 6-too post AF goats （P〈 0.01）. Pathological and electron microscopic examination revealed the disorder of myofibrils, augmentation of intercellular space, myolysis, accumulation of glycogen, and numerous bigger mitochondria among atrial cardiomyocytes in 3-mo AF goats. They recovered mostly in 6-mo post AF goats. Western blot showed that the band density oftitin significantly reduced in 3-mo AF goats compared to SR ones [1826 ± 319 vs 5012±854, P 〈 0.01]. In 3- and 6-mo post AF goats, titin increased gradually and it reversed completely in 6-mo post AF goats （3841 ± 601 and 4523 ±833 respectively, P 〈 0.01）. Conversely, the band density ofa-SMAwas significantly higher in 3-mo AF goats （5324 ± 948） than in SR ones （1619 ±271, P 〈 0.01）. In 3- and 6-mo post-AF goats, α-SMA decreased gradually, and it recovered mostly in 6- mo post AF goats （4437 ± 792 and 2205 ± 540 respectively, P〈 0.01,）. Conclusions These data indicate that the reversal of dedifferentiation of atrial cardiomyocyts is a very slow process, and it is definitely essential for normal cardiac function .     

Effect of electrical and structural remodeling on spatiotemporal organization in acute and persistent atrial fibrillation

INTRODUCTION: Atrial fibrillation (AF) may originate from discrete sites of periodic activity. We studied the effect of structural and electrical remodeling on spatiotemporal organization in acute and persistent AF. METHODS AND RESULTS: Atrial effective refractory periods (AERPs) were recorded from five different sites at baseline and after pacing in acute AF (n = 8 dogs) and persistent AF (n = 8). Four persistent AF dogs subsequently were cardioverted to sinus rhythm to allow AERP recovery. Periodicity was quantified by calculating power spectra on left atrial electrograms obtained from a 64-electrode basket catheter. Left atrial size was measured by intracardiac echocardiography and structural changes were assessed by electron microscopy. Mean AERPs decreased after pacing in acute (128 +/- 16 msec to 108 +/- 29 msec, P < 0.001) and persistent AF (135 +/- 16 msec to 104 +/- 24 msec, P < 0.0001). AERP recovery was established after 7 days of sinus rhythm. Structural changes were mild in acute AF, severe in persistent AF, and remained severe after AERP recovery. A single dominant frequency was identified in 94% of acute AF bipoles, 57% in persistent AF, and 76% after AERP recovery. Average correlation coefficient was 0.82 among acute AF bipoles, 0.63 in persistent AF, and 0.73 after AERP recovery. CONCLUSION: Transition from acute to persistent AF is associated with loss of spatiotemporal organization. A single dominant frequency recruits the majority of the left atrium in acute AF. Persistent AF, however, is associated with structural remodeling and dominant frequency dispersion. Recovery of refractoriness only partially restores spatiotemporal organization, indicating a major role for structural remodeling in the maintenance of persistent AF.     

Progressive remodeling of the atrial substrate--a novel finding from consecutive voltage mapping in patients with recurrence of atrial fibrillation after catheter ablation

Background: Atrial substrate properties have been demonstrated to be related to atrial arrhythmias. This study investigated whether the atrial substrate exhibits progressive remodeling in patients with recurrence of atrial fibrillation (AF) after catheter ablation.
Methods and Results: Fifteen consecutive AF patients (52 ± 12 years old, 12 males) underwent the same mapping technique (NavX, St. Jude Medical, Minnetonka, MN, USA) and same ablation technique for primary AF and recurrence of AF (170 ± 66 days after the first procedure). The bipolar mean peak-to-peak voltage (PPV) of the global left atrium during sinus rhythm significantly decreased in the second procedure (2.25 ± 0.62 vs. 1.79 ± 0.60 mV, P = 0.008). Also, the percentage of the surface area of the low voltage zone (LVZ; less than 0.5 mV) in the left atrium increased from 6 ± 4% to 13 ± 6% (P = 0.001) in the second procedure. There was no significant change in the right atrial bipolar mean PPV or surface area of the LVZ in the second procedure.
Conclusion: Atrial substrate remodeling with a progressive decrease in the left atrial voltage was demonstrated in patients with recurrent AF.     

慢性心房颤动患者心房组织转化生长因子-β分子重构的研究

目的　探讨风湿性心脏瓣膜病 (风心病 )心房颤动 (房颤 )患者心房组织中转化生长因子 β(transforminggrowthfactor β ,TGF β)基因转录和蛋白质表达的改变。　 方法　 4 2例风心病接受换瓣手术者分为二组 ,其中窦性心律组 2 0例 ,慢性房颤组 2 2例 (≥ 6个月 ) ,于术中获取的右心耳组织 (约 10 0mg) ,通过半定量逆转录 聚合酶链反应 (RT PCR)技术 ,测定心房组织中TGF βmRNA的相对含量 ;运用免疫组织化学方法 ,检测心房组织中TGF β的定位和蛋白相对表达量。　 结果　与窦性心律组相比 ,慢性房颤组TGF β1 mRNA相对含量增加差异有显著性 (P <0 0 0 1) ,两组间TGF β2 mRNA水平差异无显著性 (P >0 0 5 )。TGF β1 、TGF β2 在两组患者心房组织中主要表达在心房肌细胞。与窦性心律患者相比 ,慢性房颤患者的心房组织的TGF β1 蛋白表达增加差异有显著性 (P <0 0 1) ,而TGF β2 的蛋白表达差异无显著性 (P >0 0 5 )。　结论　房颤患者心房组织中TGF β1 分子重构可能是房颤时心房纤维化发生的分子机制之一 ,与房颤的发生和维持有关。     

心房颤动犬心房肌细胞2型理阿诺受体的分布和表达

目的探讨心房颤动(房颤)时心房肌细胞2型理阿诺受体表达和分布的改变。方法杂种犬10只,分为正常对照组和单纯房颤组,每组5只。单纯房颤组用起搏器进行房颤式快速起搏,起搏频率(500±20)次/min,正常对照组不植入起搏器。24周后取出心脏,用逆转录聚合酶链反应、免疫荧光染色技术检测犬心房肌细胞2型理阿诺受体在mRNA水平的表达和蛋白水平的表达和分布。结果与正常对照组比较,单纯房颤组犬2型理阿诺受体在mRNA和蛋白水平的表达明显低于正常对照组(P<0.05);在细胞质、细胞膜2型理阿诺受体分布均显著减少。结论房颤时心房肌细胞2型理阿诺受体表达下调,2型理阿诺受体可能不是心房肌细胞主要的钙信号调控的受体。     

迷走神经干预对犬心房电生理的影响

目的心房电重构可导致心房有效不应期缩短,通过测量心房有效不应期来研究迷走神经对心房电重构的影响。方法 10只成年犬给予酒石酸美托洛尔和阿托品阻断交感神经和迷走神经。分别测量心房电重构前后基础状态及迷走神经刺激下的心房有效不应期（ERP）和房颤易感窗口（VW）。结果①阿托品应用前后基础状态下的ERP无变化。阿托品应用前后迷走神经刺激下的ERP变化明显;②心房电重构后ERP：基础状态及迷走神经刺激下,无论右心房还是冠状静脉窦远端测得的ERP与重构前（阿托品应用后）ERP相比无明显差异（p值均〉0.05）;③VW的变化：阿托品应用前,迷走神经刺激下容易诱发房颤。阿托品应用后,心房电重构前后无论基础状态或迷走神经刺激均不能诱发房颤。结论迷走神经阻滞能减轻心房电重构所导致的心房不应期缩短,从而抑制迷走神经介导的房颤诱发。     

Effects of components of ischemia on the Kv4.3 current stably expressed in Chinese hamster ovary cells

We investigated the effects of three components of ischemia: external acidosis (pH=6.0), extracellular hyperkalemia ([K(+)]=20 mmol/l), and resting membrane depolarization to -60 mV, on Kv4.3 current stably expressed in Chinese Hamster Ovary cells. We used single electrode whole cell patch clamp techniques to study changes in the current elicited. External acidosis caused a positive shift in the steady state activation curve from -13.4 +/- 2.1 mV to -3.3 +/- 1.5 mV (n=8, P=0.004) and the steady state inactivation curve from -56.5 +/- 0.4 mV to -46.7 +/- 0.5 mV (n=14, P<0.0001). Acidosis also caused an acceleration of recovery from inactivation with the t(1/2) decreasing from 306 ms (95% CI 287-327 ms) to 194 ms (95% CI 182-207 ms), (n=14, P<0.05). Hyperkalemia did not affect any of these parameters. Combined acidosis and hyperkalemia produced effects similar to those seen with acidosis. Changing the holding potential from -90 mV to -60 mV with test potentials of +5 and +85 mV decreased the peak currents by 34.1% and 32.4% respectively (n=14). However, in the presence of external acidosis the decrease in peak currents induced by changing the holding potential was less marked. In acidotic bath the peak current at -60 mV was reduced by only 13.6% at a test potential of +5 mV and 12.3% at a test potential of +85 mV (n=14). Taken together our data suggest that the membrane depolarization and changes in pH which occur under ischemic conditions would be accompanied by relative preservation of Kv4.3 currents and provide a molecular basis for the observation of preserved epicardial I(to) and epicardial action potential duration (APD) shortening in ischemia.