Cs对兔窦房结细胞起搏离子流If和IK及自律活动的影响

运用微电极记录窦房结细胞动作电位及穿孔膜片箝技术记录酶解游离的窦房结细胞电流,研究兔心窦房结的起搏原理。实验结果显示,Ｃｓ对自律性动作电位的频率及４期自动除极速率仅有轻度抑制作用。在同一细胞、同一时间、同一测试电位范围内,Ｃｓ能基本阻断Ｉｆ及它的电导变化而对Ｉｋ电流无明显抑制作用。上述结果表明在兔心窦房结细胞的起博活动初期,Ｉｆ不是起搏的主要因素。     

N-乙酰半胱氨酸对犬心房快速起搏电重构的影响

目的：探讨N-乙酰半胱氨酸（NAC）对犬心房快速起搏电重构的影响。方法：取16只犬,随机分为对照组和NAC干预组。NAC组按照15mg／kg／d剂量给予NAC口服6周时间。在犬右房置入电极,快速起搏右心房,诱发房颤并维持2小时。在起搏前后分别测定有效不应期（AERP）。结果：房颤后对照组AERP显著缩短,AERP频率适应性下降（P〈0．05）;而NAC组房颤前后AERP和AERP频率适应性均无明显变化。结论：在心房快速起搏致房颤2h的模型中,NAC对心房电重构具有明显的保护作用。     

N-乙酰半胱氨酸对犬心房快速起搏电重构的影响

目的:探讨N-乙酰半胱氨酸(NAC)对犬心房快速起搏电重构的影响。方法:取16只犬,随机分为对照组和NAC干预组。NAC组按照15mg/kg/d剂量给予NAC口服6周时间。在犬右房置入电极,快速起搏右心房,诱发房颤并维持2小时。在起搏前后分别测定有效不应期(AERP)。结果:房颤后对照组AERP显著缩短,AERP频率适应性下降(P<0.05);而NAC组房颤前后AERP和AERP频率适应性均无明显变化。结论:在心房快速起搏致房颤2h的模型中,NAC对心房电重构具有明显的保护作用。     

肌浆网钙ATP酶过表达对心房颤动兔心房及L型钙通道alc蛋白表达的影响

目的探讨心肌肌浆网钙ATP酶2a（SERCA2a）基因过表达,对兔急性心房颤动（AF）的心房肌L型电压依赖钙通道蛋白alc亚单位（LVDCCalc）表达的影响。方法48只成年新西兰兔,随机分成为房颤组（AF组,n=12）、9一型腺相关病毒＋增强型绿色荧光蛋白组＋房颤组（rAAV9＋EGFP＋AF组,n=12）、9一型腺相关病毒＋肌浆网钙ATP酶2a＋增强型绿色荧光蛋白组＋房颤组（rAAV9＋SERCA2a＋EGFP＋AF组,n=12）,并设假手术组作为对照（Control组,,l=12）。rAAV9＋EGFP＋AF组和rAAV9＋SERCA2a4-EGFP4-AF组起搏前30d开胸心包腔内注射包含报告基因的rAAV9一EGFP和包含靶基因的rAAV9-SERCA2a—EGFP各500肛L（1×10”v．g／ptL）。转染30d后,AF组、rAAV9＋EGFP＋AF组和rAAV9＋SERCA2a＋EGFP＋AF组,以600BPM刺激频率,持续起搏兔右心房24h制作AF模型。处死各组动物,倒置荧光显微镜下观察右心房肌组织EGFP表达情况,行HE染色对右心房组织形态检查,应用免疫组化技述检测SERCA2a蛋白及LVDCCalc蛋白在心房肌中的表达情况。结果rAAV9＋EGFP＋SERCA2a4-AF组SERCA2a蛋白及LVDCCalc蛋白表达量显著高于AF组和rAAV9＋EGFP＋AF组（P〈0．05）,但与对照组比较差异无显著性。结论心房肌转SERCA2a基因,显著减少了急性房颤心房肌的LVDCCalc蛋白表达的降低,有逆转急性AF电重构的作用。     

肌浆网钙ATP酶过表达对心房颤动兔心房及L型钙通道a1c蛋白表达的影响

目的探讨心肌肌浆网钙ATP酶2a(SERCA2a)基因过表达,对兔急性心房颤动(AF)的心房肌L型电压依赖钙通道蛋白alc亚单位(LVDCCalc)表达的影响。方法 48只成年新西兰兔,随机分成为房颤组(AF组,n=12)、9-型腺相关病毒+增强型绿色荧光蛋白组+房颤组(rAAV9+EGFP+AF组,n=12)、9-型腺相关病毒+肌浆网钙ATP酶2a+增强型绿色荧光蛋白组+房颤组(rAAV9+SERCA2a+EGFP+AF组,n=12),并设假手术组作为对照(Control组,n=12)。rAAV9+EGFP+AF组和rAAV9+SERCA2a+EGFP+AF组起搏前30 d开胸心包腔内注射包含报告基因的rAAV9-EGFP和包含靶基因的rAAV9-SERCA2a-EGFP各500μL(1×1012v.g/μL)。转染30 d后,AF组、rAAV9+EGFP+AF组和rAAV9+SERCA2a+EGFP+AF组,以600 BPM刺激频率,持续起搏兔右心房24h制作AF模型。处死各组动物,倒置荧光显微镜下观察右心房肌组织EGFP表达情况,行HE染色对右心房组织形态检查,应用免疫组化技述检测SERCA2a蛋白及LVDCCalc蛋白在心房肌中的表达情况。结果 rAAV9+EGFP+SERCA2a+AF组SERCA2a蛋白及LVDCCalc蛋白表达量显著高于AF组和rAAV9+EGFP+AF组(P<0.05),但与对照组比较差异无显著性。结论心房肌转SERCA2a基因,显著减少了急性房颤心房肌的LVDCCa1c蛋白表达的降低,有逆转急性AF电重构的作用。     

乙酰胆碱对豚鼠心房肌和心室肌的动作电位和收缩力的不同作用

实验采用标准玻璃微电极细胞内记录技术记录心肌细胞动作电位（action potential,AP）、肌力换能器记录心肌收缩力（force contraction,Fc）,研究乙酰胆碱（acetylcholine,ACh）对离体豚鼠心房肌、心室肌的作用。结果表明,10μmol/L ACh可缩短心房肌、心室肌动作电位的时程（action potential duration,APD）。心房肌APD在给药前后分别为208.57±36.05ms及101.78±14.41ms（n=6,P<0.01）,心室肌APD在给药前后分别为286.73±36.11ms及265.16±30.06 ms（n=6,P<0.01）。心房肌动作电位的幅度（action potential amplitude,APA）也降低,给药前后分别为88.00±9.35 mV及62.62±20.50 mV（n=6,P<0.01）,而心室肌APA无明显变化。ACh还降低心房肌、心室肌的收缩力,心房肌、心室肌Fc的抑制率分别为100％（n=6,P<0.01）和37.57±2.58％（n=6,P<0.01）。ACh对心房肌、心室肌APD和Fc的抑制作用在一定范围内（1nmol/L～100μmol/L）随ACh浓度的增高而增强。用Scott法求出ACh对心房肌、心室肌APD缩短作用的KD值,分别为0.275和0.575μmol/L,对Fc抑制作用的KD值分别为0.135和0.676μmol/L。各浓度下ACh对心房肌效应与心室肌效应作组间t检验,从10nmol/L到0.1mmol/L均有显著的统计学差异。此外,10μmol/L阿托品及20mmol/L     

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     

α-人心房钠尿因子对离体豚鼠心肌收缩力和动作电位时程的影响

为探讨α-人心房钠尿因子(α-human atrial natriuretic factor,α-hANF)对心脏的直接作用,本工作在离体豚鼠心室肌标本上观察了。a-hANF 对乳头肌收缩力和动作电位时程(APD)的影响。结果表明,20 nmol/L 和40 nmol/L a-hANF 均可明显抑制乳头肌收缩幅度(CA)和收缩相上升速率)(dA/dt),在40 nmol/L a-hANF 作用20min 后,APD 缩短明显。提示α-hANF 对心肌收缩力和 APD 具有直接抑制作用。     

甲磺胺心定对家兔窦房结心房肌房室结与希氏束细胞动作电位的影响

在离体家兔右心房-房中隔与房室结-希氏束标本上,用微电极技术研究了β-受体阻断剂甲磺胺心定(Sot)对窦房结(SAN)、心房肌、房室结(AVN)、希氏束细胞的电生理效应。Sot(1.6×10~(-6)—1.6×10~(-4)M)对上述4种细胞的动作电位振幅和0相最大除极速度皆无影响。Sot 能显著减慢 SAN 与 AVN 的自搏频率,并延长自律恢复时间。标本被驱动时,心房SAN 逆传时间与房-室传导时间均被 Sot 延长。Sot 还能显著延长上述4种细胞的动作电位时程与有效不应期,并且是浓度依赖性的。β-受体阻断剂甲氧乙心安(Met,1.2×10~(-7)—1.2×10~(-4)(M)对这些指标无影响。说明 Sot 尚具有第三类抗心律失常药物的特性。此外在8只标本上用期前刺激诱发了动作电位的快速自动发放,这是折返性室上性心动过速的电生理基础。Met 仅对1例有效,Sot 能全部制止其余7例的 AP 自动发放。这显然是由于 Sot 延长了细胞复极化过程和不应期,阻断了折返兴奋的传播,从而显示其优于β-受体阻断剂的抗心律失常效果。     

心室不同部位起搏对正常犬和扩张型心肌病心力衰竭犬模型在体心肌跨室壁复极离散的影响

实验以正常犬和扩张型心肌病心力衰竭犬(dilated cardiomyopathy congestive heart failure,DCM-CHF)模型为对象、以心肌跨室壁复极离散的相关参数为指标,研究左心室心外膜起搏、双心室起搏(模拟临床上心室再同步治疗的方法)后的心肌电生理特性变化。实验以快速右心室起搏的方法制备DCM-CHF犬模型;正常犬和DCM-CHF犬均经射频消融希氏束制备三度房室传导阻滞模型;采用同步记录犬体表心电图和内膜下、中层、外膜下三层心肌单相动作电位(monophasic action potentials,MAP)的方法,测定不同部位起搏时的QT间期、Tpeak-Tend(Tp-Te)间期和三层心肌的单相动作电位时程(MAP duration,MAPD)、跨室壁复极离散度(transmural dispersion of repolaization,TDR)。结果显示:在正常犬,左室心外膜与双心室起搏后三层心肌的MAPD均延长,同时TDR增大(左室心外膜起搏47.16 ms、双心室起搏37.54 ms、右室心内膜起搏26.75 ms,P<0.001),体表心电图Tp-Te间期的变化与之平行;在DCM-CHF犬较正常犬已表现出中层心肌MAPD延长(276.30 ms vs 257.35 ms,P<0.0001)和TDR(33.8 ms vs 27.58 ms,P=0.002)增大的基础上,左室心外膜参与起搏后仍进一步使三层心肌的MAPD延长和TDR增大。研究结果提示,左室心外膜起搏和双心室起搏后使内膜下、中层     

Evaluation of Bachmann Bundle Pacing Versus Right Atrial Pacing in Prevention of Atrial Fibrillation After Coronary Artery Bypass Surgery

Background

In patients undergoing coronary artery bypass surgery (CABGS), occurrence of atrial fibrillation (AF) is common in the postoperative period and is associated with increased morbidity with longer intensive unit care (ICU) and hospital stay. Prevention with antiarrhythmic drugs is of limited success and associated with significant side effects. Therefore alternative approaches, such as Bachmann Bundle pacing, are required.

Methods and Results

154 consecutive patients, mean age 58±8.8 years, including 134 males and 20 females, were randomized to three groups; Group I : No pacing n= 54, Group II : RA pacing n= 52, Group III : Bachmann Bundle pacing n= 48. All the groups were well matched with regard to age, left atrial size, ejection fraction and use of beta blockers. Patients in Groups II and III were continually paced at a rate of 100 beats per minute (bpm) or at 10 bpm more than patients'' intrinsic heart rate. All the patients were monitored for 72 hours by telemetry and occurrence of AF was noted. Incidence of AF was 0% (none of 48 patients) in Group III as compared to 16.6% in Group I (9 of 54 patients) (p 0.003) and 12.5% in Group II (5 of 52 patients) (p 0.03). There was a trend towards shorter ICU stay in Group III (3.9 days) as compared to Group II (4.5 days) and Group I (4.1 days). Among the three groups, the reduction in mean P wave duration also was greater in Bachmann bundle paced group.

Conclusion

In patients undergoing CABGS, Bachmann bundle pacing is superior to right atrial / no pacing in the post operative period for preventing occurrence of AF and reducing ICU stay, commensurate with a reduction in mean P wave duration on surface ECG.     

经食道心房调搏术及食道心电图在心律失常中的应用

目的:分析经食道心房调搏术(TEAP)及食道内心电图(EECG)在心律失常中的应用价值。方法:选取2018年6月至2019年12月于我院行食道心电图及经食道调搏的患者189例,其中男80例,女109例,年龄11~83岁。结果:54例为房室结折返性心动过速(AVNRT),34例为房室折返性心动过速(AVRT),8例为房性心动过速(AT),4例为心房扑动(AF),6例为心房颤动(Af),5例为室性心过速,78例为室早或其他。共105例心律失常患者拟行食道心房调搏终止心动过速,所有AVNRT和AVRT患者及17例AT患者经食道心房调搏S1S1成功转为窦律,50例AVNRT、32例AVRT、6例AT、3例AF及2例VT患者通过射频消融术成功根治。其中1例11岁AT患者因无法耐受食道调搏,未能转为窦律,患者经静推普罗帕酮后次日转为窦律。共97例患者拟行食道心房调搏诱发,共49例诱发出心动过速,1例左后分支型室速经静滴异丙肾上腺素后诱发心动过速,且仍需静滴异丙肾上腺素后经心房食道调博终止心动过速,后经射频消融术成功根治。结论:TEAP及EECG可用于复杂心律失常的诊断及治疗,是一种相对安全、临床容易掌握的技术,值得推广。     

辣椒素对大鼠肠系膜下神经诱发动作电位的影响

目的:探讨辣椒素对肠系膜下神经诱发动作电位的影响。方法:对大鼠肠系膜下神经节施加不同浓度(分别为2.5、5、10g/L)的辣椒素或其载体(对照)后,在其中枢端给予能引起反应的方波刺激,记录节后神经外周端的动作电位。结果:虽然实验动物存在个体差异,且辣椒素对其神经作用的阈值也有所不同,但在大多数情况下,当辣椒素浓度为2.5～5g/L、作用3min后,即可使神经的敏感性降低;并表现出了较为明显的剂量相关性,即随着辣椒素浓度的升高,其对神经的脱敏作用也逐渐增强。结论:辣椒素对肠系膜下神经节内的交感和副交感神经均具有抑制作用。     

术前使用左心耳3D模型及左心耳封堵体外模拟治疗心房颤动患者的疗效

摘要 目的：探讨术前使用左心耳3D模型及左心耳封堵体外模拟治疗心房颤动患者的疗效。方法：回顾性选择2021年1月至2022年10月来我院诊治的心房颤动患者,对照组行经食管超声心动图检查、心脏CT造影检查及左心耳封堵术。观察组行经食管超声心动图检查、心脏CT造影检查、基于心脏CT造影数据打印左心耳3D模型、应用3D打印模型进行左心耳封堵体外模拟演练及左心耳封堵术,对比两组相关指标。结果：两组经食管超声心动图检查左心耳各径线对比无差异（P>0.05）。两组经CT检查左心耳各径线对比无差异（P>0.05）。两组封堵器固定大小对比有差异（P<0.05）。术后经食管超声心动图检查发现,观察组术后3个月及12个月血流通过封堵器几率高于对照组,但组间对比无差异（P>0.05）。术后3个月及12个月时,两组的左心房内径降低,且同时间点观察组较对照组（P<0.05）;两组术后3个月及12个月时左心室内径对比无差异（P>0.05）。观察组的封堵器型号匹配率较对照组高,手术操作时间、X线曝光量、造影剂使用量、封堵器术中释放次数较对照组低（P<0.05）,观察组的残余分流及手术并发症较对照组低,但组间对比无差异（P>0.05）。观察组术后3个月封堵器位置、有无残腔及不良心血管事件与对照组相比无差异（P>0.05）,术后12个月,封堵器位置良好率较对照组低（P<0.05）,其余两组间对比无差异（P>0.05）。结论：术前使用左心耳3D模型及左心耳封堵体外模拟可提高心房颤动患者的疗效。     

Cardiac expression and atrial fibrillation-associated remodeling of K2P2.1 (TREK-1) K channels in a porcine model

Aims

Effective management of atrial fibrillation (AF) often remains an unmet need. Cardiac two-pore-domain K⁺ (K_2P) channels are implicated in action potential regulation, and their inhibition has been proposed as a novel antiarrhythmic strategy. K_2P2.1 (TREK-1) channels are expressed in the human heart. This study was designed to identify and functionally express porcine K_2P2.1 channels. In addition, we sought to analyze cardiac expression and AF-associated K_2P2.1 remodeling in a clinically relevant porcine AF model.

Main methods

Three pK_2P2.1 isoforms were identified and amplified. Currents were recorded using voltage clamp electrophysiology in the Xenopus oocyte expression system. K_2P2.1 remodeling was studied by quantitative real time PCR and Western blot in domestic pigs during AF induced by atrial burst pacing.

Key findings

Human and porcine K_2P2.1 proteins share 99% identity. Residues involved in phosphorylation or glycosylation are conserved. Porcine K_2P2.1 channels carried outwardly rectifying K⁺ currents similar to their human counterparts. In pigs, K_2P2.1 was expressed ubiquitously in the heart with predominance in the atrial tissue. AF was associated with time-dependent reduction of K_2P2.1 protein in the RA by 70% (7 days of AF) and 80% (21 days of AF) compared to control animals in sinus rhythm. K_2P2.1 expression in the left atrium, AV node, and ventricles was not affected by AF.

Significance

Similarities between porcine and human K_2P2.1 channels indicate that the pig may represent a valid model for mechanistic and preclinical studies. AF-related atrial K_2P2.1 remodeling has potential implications for arrhythmia maintenance and antiarrhythmic therapy.     

Abbreviated Action Potential Kinetics in a Mouse Model of Potassium Channel Overexpression During Hippocampal Development

Loss or "gain" of function mutations in voltage-gated ion channels often results in an adverse neurological phenotype. We have examined the electrical characteristics of hippocampal pyramidal cells in a transgenic mouse model to determine how overexpression of a Shaker-type potassium channel subunit during early postnatal development might alter excitability properties of developing neurons. We found that in CA3 neurons potassium channel overexpression led to a transient shortening in duration of single action potentials during the first two postnatal weeks. There was an increase in maximal repolarization rate, without significant effect on the rate of rise. Transgenic CA3 neurons also showed a decrease of firing frequency in response to sustained depolarizing current injection. In contrast, repolarization of action potentials in CA1 neurons was not significantly altered by trangene expression. Western Blot Analysis of membrane-associated transgene protein indicated that transgene protein levels decreased during development, in agreement with functional measures of spike width. Our data indicate that the functional consequences of potassium channel transgene expression are dependent on cellular environment and developmental stage. A transient period of hypoexcitability during a critical period of development for CA3 neurons may contribute to the hyperexcitable phenotype observed in adult animals.     

左房内径、血清尿酸水平与老年心房颤动的相关性分析

目的:探讨左房内径(LAD)、血清尿酸(UA)水平与老年心房颤动的相关性。方法:选择2013年1月至2016年7月在我院住院的60岁以上的非瓣膜性房颤患者,共166例,其中持续性房颤组85例,阵发性房颤组81例,选择同期无房颤的高血压、冠心病老年患者83例作对照组。通过心脏彩超检查检测LAD、左心室舒张末期内径(LVDD)、左心室收缩末期内径(LVDS)、左心室射血分数(LVEF),以≥40 mm为左房内径增大。并采用生化分析检测患者血清UA水平。结果:(1)持续性房颤组LAD、LVEF、左心房增大发生率均显著高于阵发性房颤组和对照组,而阵发性房颤组以上指标均明显高于对照组,差异具有统计学意义(P0.05)。(2)持续性房颤组和阵发性房颤组患者血清UA水平均显著高于对照组,但持续性房颤组和阵发性房颤组之间血清UA水平比较差异无统计学意义(P0.05)。结论:左心房内径大小、血尿酸水平与老年患者心房颤动的发生密切相关。     

益气养阴活血化瘀方对心力衰竭合并房颤患者血清CRP，BNP，CK-MB及cTnI水平的影响及其疗效观察

目的:探讨益气养阴活血化瘀方治疗心力衰竭合并房颤的临床疗效。方法:收集2014年3月-2015年9月我院收治的158例充血性心力衰竭合并房颤的患者158例为研究对象,随机分为对照组和实验组,每组79例。对照组患者采取常规治疗,实验组患者采用益气养阴活血化瘀方治疗。观察并比较两组患者治疗前后超敏C反应蛋白(CRP)、脑钠素(BNP),CK-MB及肌钙蛋白(cTnI)水平的变化情况。结果:治疗后,与对照组相比,实验组LVEDD、LVESD明显低于对照组,而LVEF明显增高,差异具有统计学意义(P0.05);治疗后实验组患者的CK-MB、pro-BNP、cTnI及CRP水平明显低于对照组,差异具有统计学意义(P0.05)。实验组随访末期死亡率、非致死性心力衰竭及心源性休克发生率均低于对照组,差异具有统计学意义(P0.05);随访末期内建立侧支循环明显多于对照组,差异具有统计学意义(P0.05)。结论:益气养阴活血化瘀方可以有效抑制充血性心力衰竭合并房颤患者术后心脏重塑,改善左心室收缩功能,降低不良事件发生。