迷走神经介导性心房颤动和六小时快速起搏介导性心房颤动的回复性质研究

目的 在迷走神经介导性心房颤动(房颤)和6h快速起搏介导的房颤模型中研究心房动作电位时限(APD)的回复性质.方法 18只犬随机分为迷走神经介导性房颤组(A组,n=8)和6h快速起搏介导性房颤组(B组,n=10).两组犬麻醉后开胸,暴露心脏,分别在多个肺静脉及心房部位记录单相APD.以APD复极90％(APD90)的时间为纵坐标、以其前的舒张间期为横坐标构建不同部位的APD回复曲线.结果 在A组,迷走神经刺激显著缩短每一部位的APD90、使回复曲线变平坦(斜率＜1)并抑制APD交替的发生,但同时迷走神经刺激增加房颤的诱发性和持续时间[(13±3)s对(5±1)s,P＜0.05].在B组,6h快速起搏缩短APD、使回复曲线变陡峭(斜率＞1)并促进APD交替的发生,同时房颤的发生率和持续时间增加[(10±3)s对(5±1)s,P＜0.05].结论 迷走神经介导性房颤和6h快速起搏介导的房颤具有不同的回复性质,提示不同机制的房颤具有不同的心房回复性质.     

迷走神经和肺静脉刺激对心房肌动作电位和乙酰胆碱激活钾电流的影响

目的研究迷走神经和肺静脉快速刺激对心房肌动作电位和乙酰胆碱激活钾电流的影响。方法24只犬随机分为3组,每组8只犬。对照组：采用20Hz频率和0．2ms波宽刺激迷走神经,观察诱发心房颤动（房颤）情况。左上肺静脉（LSPV）刺激组：快速刺激LSPV4h,观察刺激前后左有心房和LSPV动作电位时限（APD）的变化,随后行迷走神经刺激,观察诱发房颤情况。迷走神经干预组：先采用5Hz频率、0．2ms波宽和5～10V电压刺激迷走神经30min,然后快速刺激LSPV4h,观察刺激前后APD的变化,冉迷走神经刺激观察诱发房颤情况。所有犬在电生理检测后开胸取心脏,分离LSPV和左右心房肌细胞,采用膜片钳技术观察乙酰胆碱激活钾电流（IK,ACh）变化。结果LSPV刺激组,APD。明显缩短,动作电位时限高散度（dAPD90）明显增加[（5±3）msVS（14±5）ms,P〈0．05]。迷走神经干预组,APD。无明显变化,但APD90-d明显增加[（6±3）mvs vs（12±5）ms,P〈0．05]。与对照组相比,LSPV刺激组细胞Ik、ACh明显增加,但对照组与迷走神经干预组相比,IK．ACh差异无统计学意义。结论APD缩短是胆碱能房颤诱发的基础,肺静脉快速刺激可增加IK．ACh密度,快速刺激前行迷走神经能阻止电重构的发生。     

消融犬右肺静脉脂肪垫对心房及右上肺静脉电生理特性及房颤诱发的影响

目的探讨消融右肺静脉脂肪垫对心房及右上肺静脉电生理特性及房颤诱发的影响。方法犬18只分别在颈部迷走神经未刺激和刺激的情况下,观察射频消融肺静脉脂肪垫前后心房不同部位及右上肺静脉有效不应期、房颤诱发率及房颤诱发窗口的变化。结果在刺激迷走神经的情况下,与消融前相比,消融后高位右心房有效不应期延长（P<0.05）,其余部位有效不应期无显著差异,消融后高位右心房房颤诱发率降低（P<0.01）,房颤诱发窗口变窄（P<0.05）,左心房（P<0.01）及右上肺静脉（P<0.01）房颤诱发率升高,诱发窗口增宽。同时,心房有效不应期离散度增加（P<0.01）。结论消融右肺静脉脂肪垫使高位右心房房颤诱发率降低及房颤诱发窗口变窄,却使左房、右上肺静脉房颤诱发率升高及房颤诱发窗口增宽。     

迷走神经刺激对心房颤动影响的双重作用

迷走神经刺激（VNS）可通过缩短心房有效不应期（AERP）和动作电位时程（APD）、增加AERP和APD离散度、促进心房电重构等机制诱发和维持心房颤动（简称房颤）,但最近有实验表明VNS除了致房颤作用外,在一定条件下具有治疗作用,低强度VNS可以抑制房颤的诱发,选择性房室结VNS可以控制房颤时快速心室率,但VNS治疗房颤的作用还面临着一些问题,仍需进一步研究。     

自主神经系统与心房颤动关系及心脏神经丛消融疗效再认识

①刺激迷走神经或心脏神经丛(GP)可引起心房或肺静脉不应期缩短并诱发心房颤动(简称房颤);消融GP可消除心房或肺静脉诱发房颤的能力;刺激犬GP或在犬GP内注射乙酰胆碱可诱发复杂碎裂心房电图(CFAE),消融犬或房颤病人GP或使用自主神经阻断剂可使CFAE消失或减弱,提示自主神经与房颤关系密切。②单独或附加消融GP治疗房颤的成功率约40%~90%。入选病例、消融方法、GP定位、去神经程度、成功标准、随访方案、术者经验等均可能是形成疗效差异的因素,但高频电刺激定位GP的敏感性欠高可能是一个重要的影响因素,故解剖定位GP可能会得到更多关注。③GP消融后神经组织是否再生尚无定论,但部分消融GP所致的不平衡神经重构可能是房颤再发的重要因素之一。     

稳心颗粒对心房神经节消融后心房颤动的影响机制

目的 探讨口服稳心颗粒对犬心房神经节（GP）消融后心房颤动（房颤）诱发的影响.方法 19只犬随机分为假手术组、GP消融组和稳心颗粒组.所有犬左侧第4肋间开胸,右心房短阵快速起搏观察房颤诱发情况.假手术组电生理监测后关胸,GP消融组和稳心颗粒组开胸后消融心房左、右GP,所有犬喂养8周,其中稳心颗粒组给予稳心颗粒0.25g·kg-1 ·d-1.8周后再次观察房颤诱发和心房基质变化.结果 与假手术组和稳心颗粒组相比,GP消融组8周后房颤诱发率明显升高.GP消融组犬血浆脑钠钛（BNP）明显增高[（142.2±21.4）pg/ml对（259.3±34.5）pg/ml,P＜0.01],而稳心颗粒组的BNP水平在消融8周后降低,但差异无统计学意义;3组犬在开胸前和喂养8周后血肿瘤坏死因子（TNF-α）和白细胞介素6（IL-6）无明显变化;与假手术组相比,GP消融组8周后左右心房肌组织中的BNP,TNF-α和IL-6水平明显增加,左心房组织的BNP,TNF-α和IL-6水平分别为[（117.1±15.2） pg/mg对（121.3±14.9）pg/mg,P＞0.05; （91.3±35） pg/mg对（180.3±72） pg/mg,P=0.02; （125.3±42） pg/mg对（273.3±83）pg/mg,P＜0.01];右心房组织的BNP,TNF-α和IL-6水平分别为[（143.6±33.7） pg/mg对（206.2±41.4） pg/mg,P=0.02;（75.3 12.1）pg/mg对（141.3±64） pg/mg,P=0.03;（175.1±42.5）pg/mg对（351.7±101）pg/mg,P＜0.01].假手术组和稳心颗粒组心房肌组织中的BNP,TNF-α和IL-6水平差异无统计学意义.结论 长期口服稳心颗粒可抑制心房GP消融后基质重构和房颤的诱发.     

低强度神经节丛刺激对正常心室电生理性质和急性心肌缺血室性心律失常发生的影响

目的 研究低强度神经节丛(GP)刺激对正常心室电生理性质和急性心肌缺血室性心律失常发生的影响.方法 体重18～25kg的正常成年杂种犬39只随机分为正常心脏组(n=12)和急性心肌缺血组(n=27,其中对照组12只,低强度GP刺激组15只),以2根多极电生理导管记录左、右心室局部电图,以自制Ag-AgC1电极记录左、右心室单相动作电位.在正常犬,分别在6h低强度GP刺激前和刺激后测量心室各部位有效不应期(ERP)、动作电位时限(APD),APD回复性质和APD交替以及血清乙酰胆碱和去甲肾上腺素浓度;在急性心肌缺血犬,比较室性心律失常的发生情况.结果 在正常犬,6h低强度GP刺激显著延长心室各部位ERP及APD(P＜0.05),但未改变其空间离散度;6h低强度GP刺激促进APD交替发生但不改变APD回复曲线斜率及其空间离散度;6h低强度GP刺激后血清去甲肾上腺素和乙酰胆碱水平均显著增加(P＜0.05).在急性心肌缺血犬,低强度GP刺激组室性心律失常的发生率显著低于对照组(P＜0.05).结论 低强度GP刺激不增加正常心脏室性心律失常的风险且有助于抑制急性心肌缺血心脏室性心律失常的发生.     

自主神经与心房颤动发生的研究状况

心脏受迷走神经和交感神经的双重自主神经支配,其在心房颤动(简称房颤)的发生和发展过程中有不同作用。迷走神经刺激有缩短心房有效不应期、缩短动作电位时程以及增加动作电位时程离散度的效应,增加房颤的可诱发性。乙酰胆碱存在时,快速刺激易诱发房颤。交感神经主要通过增加心房、肺静脉、Marshall韧带等部位的异位电活动增加房颤可诱发性。心交感神经和心迷走神经平时都有一定程度的冲动发放,两者相互影响、相互抑制,在心脏的神经调节中共同发挥作用,并且也是房性心律失常常见的触发因素。     

电刺激犬心室神经节丛对自主神经介导房颤的影响

目的 本研究探讨低频电刺激心室主动脉根部神经节丛（ganglionated plexi,GP）对肺静脉源性房颤(AF)诱发率的影响。方法 20只犬分别测量基础状态下,高频和低频电刺激主动脉根部GP时的心房有效不应期和肺静脉有效不应期。分别在基础状态下,高频和低频电刺激主动脉根部GP时,自肺静脉远端以程序刺激诱发AF和AF诱发率的变化。结果 高频电刺激主动脉根部GP 明显缩短心房的肺静脉的有效不应期,增加AF的诱发率。而低频电刺激使心房及肺静脉有效不应期呈延长趋势,并降低AF诱发率。结论 低频电刺激主动脉根部GP降低自主神经介导的AF诱发率。     

心房神经节消融后心房结构重构与心房颤动诱发的关系

目的研究心房心外膜神经节丛（GP）消融后心房基质的变化,探讨其与心房颤动（房颤）诱发的关系。方法10只犬随机分为假手术组和GP消融组。所有犬均行超声心动图后无菌下右侧开胸,观察右心房短阵快速电刺激诱发房颤情况。之后GP消融组分别消融心房右前和右下GP,消融后即刻观察右心房短阵快速电刺激诱发房颤情况。所有犬喂养8周后,同样方法再观察房颤诱发情况。取出心脏分离左、右心房肌组织,采用放射免疫法检测脑钠肽（BNP）水平及免疫组化法检测神经密度;同样方法检测犬开胸前和开胸后8周血浆BNP水平和超声心动图。结果假手术组和GP消融后即刻右心房刺激未能诱发出房颤,但房颤在GP消融后8周易诱发;血浆和右心房组织BNP水平在GP消融后8周明显升高[（119．5±22．6）pg／mlV8（167．7±26．4）pg／ml,（213．2±34．9）pg／gVS（287．6±36．4）pg／g,P〈0．05],但左心房BNP水平无明显变化;两组犬术前和术后左右心房大小均无明显变化;GP消融8周后右心房GAP43、TH和ChAT阳性纤维的密度低于假手术组,差异有统计学意义[（791±714）permm2vs（2540±863）permm2,（448±582）permm。VS（1855±623）permm2,（580±726）permm2vs（2833±851）permm2,P〈0．05],但左心房无明显变化。结论心房心外膜GP消融后,心房基质发生重构,可能是GP消融后房颤易诱发的原因。     

The effects of atrial ganglionated plexi stimulation on ventricular electrophysiology in a normal canine heart

Aims

Atrial ganglionated plexi (GP) have been shown to modulate atrial electrophysiology and play an important role in atrial fibrillation initiation and maintenance. The purpose of this study was to investigate the effects of atrial GP stimulation (GPS) on ventricular refractoriness, restitution properties and electrical alternans.

Methods

In 12 anesthetized dogs, two multiple electrode catheters were sutured at left and right ventricular free walls for recording. Monophasic action potentials were recorded from six epicardial ventricular sites. Ventricular effective refractory period (ERP), action potential duration (APD) restitution properties and APD alternans were measured at baseline and during GPS.

Results

Compared with baseline, GPS significantly prolonged ventricular ERP and APD at all sites and decreased their spatial dispersions (P?<?0.05 for all). GPS also significantly flattened ventricular restitution curves and decreased the maximal slope of restitution curves at each site (P?<?0.05 for all). APD alternans occurred at shorter pacing cycle length at each site during GPS when compared with baseline (P?<?0.05 for all).

Conclusions

GPS prolonged ventricular ERP, decreased the slope of restitution curves and delayed APD alternans, indicating that GPS may exert a protective role for ventricular arrhythmias.     

Inducibility of Atrial Fibrillation After GP Ablations and “Autonomic Blockade”: Evidence for the Pathophysiological Role of the Nonadrenergic and Noncholinergic Neurotransmitters

Autonomic Blockade and Atrial Fibrillation . Background: Recent clinical reports that used cholinergic and adrenergic blockade (CAB) as an alternative to ganglionated plexi (GP) ablation to terminate atrial fibrillation (AF) showed mixed results. We investigated the role of other neurotransmitters in AF inducibility. Methods: In 23 pentobarbital anesthetized dogs, a left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins and atrial appendages (AA). Programmed stimulation was used to determine the effective refractory periods (ERP) and AF inducibility, measured by the window of vulnerability (WOV). AF duration in response to acetylcholine (Ach; 100 mM) applied to the AA was measured before and after GP ablation + CAB and with vagus nerve stimulation (VNS). After GP ablation + CAB, Ach induced AF duration was determined in response to vasoactive intestinal peptide (VIP) and its specific antagonist ([Ac‐Tyr1,D‐phe2]‐VIP). Results: GP ablation + CAB significantly prolonged ERP, eliminated WOV, and suppressed the duration of Ach induced AF (P ≤ 0.01 for all). Also slowing of the heart rate by VNS was essentially blocked; however, with Ach 100 mM applied to the AA, VNS, and VIP applied to the AA markedly prolonged AF duration. This effect was blocked by the VIP antagonist. Conclusions: Neither GP ablation nor CAB can fully suppress AF inducibility arising from the atrial neural network. Our findings suggest that other neurotransmitters, such as VIP released during VNS, can promote sustained AF despite GP ablation and “autonomic blockade,” which may further define the substrate for AF outside the pulmonary vein‐atrial junctions. (J Cardiovasc Electrophysiol, Vol. 24, pp. 188‐195, February 2013)     

神经节丛消融对心室不应期和室性心律失常发生的影响

目的 研究心脏神经节丛(GP)消融对心室不应期和室性心律失常发生的影响.方法 24只杂种犬随机分为GP消融组(n=12)和对照组(n=12).在左、右心室表面分别缝一10极冠状静脉窦电极导管记录心底部至心尖部4个不同部位电图,分别测量各个部位GP消融前和消融后伴或不伴迷走神经刺激时的有效不应期(ERP),测量ERP的空...     

序列消融犬窦房结脂肪垫和房室结脂肪垫对迷走神经介导心房颤动诱发的影响

目的 研究旨在探索序列消融窭房结脂肪垫(sinus atrial node fat pad,SANFP)和房室结脂肪垫(atrialventricular node fat pad,AVNFP)对迷走神经介导的心房颤动(房颤)诱发的影响.方法 18只健康成年家犬分为二组,每组9只.A组优先消融SANFP,再联合消融SANFP+ AVNFP;B组优先消融AVNFP,再联合消融SANFP+ AVNFP.高频电刺激左、右侧迷走神经干制作迷走神经介导的房颤模型,测定消融前、后的房颤诱发率及心房和肺静脉不同部位有效不应期(effective refractory period,ERP).结果 (1)迷走神经干刺激可显著增加房颤的诱发率,且右侧迷走神经干刺激下的房颤诱发率高于左侧迷走神经干[(60.0±0.0)％比(18.4±22.1)％].(2)优先消融SANFP可显著降低左侧迷走神经干或右侧迷走神经干刺激下房颤的诱发率(分别降低了67.0％和72.0％),联合消融SANFP+ AVNFP可进一步降低2V电压的左侧迷走神经干或右侧迷走神经干刺激下房颤的诱发率(分别较消融前降低了100％和95.5％).而优先消融AVNFP也可显著降低2V电压的左侧迷走神经干或右侧迷走神经干刺激下房颤的诱发率(分别降低了95.7％和96.3％),但联合消融SANFP+ AVNFP并不进一步显著降低左侧迷走神经干或右侧迷走神经干刺激下的房颤诱发率(分别较消融前降低了98.0％和100％).(3)优先消融SANFP或AVNFP均可显著抑制迷走神经干刺激引起的右房、左房及右上肺静脉部位的ERP缩短效应.与单独消融SANFP相比,联合消融SANFP+AVNFP可进一步抑制迷走神经干刺激引起右房ERP的缩短效应,而联合消融AVNFP+ SANFP对迷 走神经干刺激引起左、右心房及肺静脉ERP的缩短效应的抑制作用与单独消融AVNFP比较差异无统计学意义.结论 心外膜脂肪垫消融可改变迷走神经干刺激对房颤诱发及心房肌、肺静脉ERP的影响,其中AVNFP是迷走神经干支配心房的汇聚点和主控区,因此AVNFP可能是房颤神经消融更有效的靶点.     

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.     

Evaluation of catheter ablation of periatrial ganglionic plexi in patients with atrial fibrillation

Recent data suggests that the cardiac autonomic nervous system has an important role in the initiation and maintenance of atrial fibrillation (AF). This study investigated (1) the feasibility of identifying and targeting these autonomic ganglia using endocardial radiofrequency stimulation and ablation, respectively; (2) the efficacy of endocardial ablation to completely eliminate the vagal response elicited from epicardial stimulation; and (3) the effect of autonomic ablation on the acute inducibility of AF. The study included 18 patients referred for catheter ablation of suspected vagal-mediated AF. The endocardial left atrial surface was stimulated at high frequency (20 to 50 Hz) to elicit a vagal response. In selected patients (n = 5), pericardial access was obtained using a subxyphoid puncture to permit epicardial stimulation. Catheter ablation of the putative autonomic ganglionic sites was performed from the left atrial endocardium using irrigated radiofrequency energy. After ablation of all identifiable autonomic ganglia, high-frequency pacing was repeated to induce AF. In all patients, stimulation at certain endocardial sites elicited a vagal response. Endocardial ablation abrogated this vagal responsiveness. Furthermore, for sites accessible from the pericardium, the vagal response elicited using epicardial stimulation was also eliminated. Despite successful ablation of these ganglia, AF was still inducible in 17 of 18 patients. In conclusion, successful ablation of autonomic ganglia from an endocardial approach can be reliably achieved using an irrigated catheter. In addition, ablation of these structures in patients with vagal-mediated AF is insufficient to prevent its acute reinduction with high-frequency atrial stimulation.     

Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation.

OBJECTIVES: This study sought to systematically investigate the interactions between the extrinsic and intrinsic cardiac autonomic nervous system (ANS) in modulating electrophysiological properties and atrial fibrillation (AF) initiation. BACKGROUND: Systematic ganglionated plexi (GP) ablation to evaluate the extrinsic and intrinsic cardiac ANS relationship has not been detailed. METHODS: The following GP were exposed in 28 dogs: anterior right GP (ARGP) near the sinoatrial node, inferior right ganglionated plexi (IRGP) at the junction of the inferior vena cava and atria, and superior left ganglionated plexi (SLGP) near the junction of left superior pulmonary vein and left pulmonary artery. With unilateral vagosympathetic trunk stimulation (0.6 to 8.0 V, 20 Hz, 0.1 ms in duration), sinus rate (SR), and ventricular rate (VR) during AF were compared before and after sequential ablation of SLGP, ARGP, and IRGP. RESULTS: The SLGP ablation significantly attenuated the SR and VR slowing responses with right or left vagosympathetic trunk stimulation. Subsequent ARGP ablation produced additional effects on SR slowing but not VR slowing. After SLGP + ARGP ablation, IRGP ablation eliminated VR slowing but did not further attenuate SR slowing with vagosympathetic trunk stimulation. Unilateral right and left vagosympathetic trunk stimulation shortened the effective refractory period and increased AF inducibility of atrium and pulmonary vein near the ARGP and SLGP, respectively. The ARGP ablation eliminated ERP shortening and AF inducibility with right vagosympathetic trunk stimulation, whereas SLGP ablation eliminated ERP shortening but not AF inducibility with left vagosympathetic trunk stimulation. CONCLUSIONS: The GP function as the "integration centers" that modulate the autonomic interactions between the extrinsic and intrinsic cardiac ANS. This interaction is substantially more intricate than previously thought.     

消融犬Marshall韧带对刺激心房左后脂肪垫所致心房颤动的影响及机制

目的探讨消融犬Marshall韧带对刺激心房左后脂肪垫所致心房颤动(简称房颤)的影响及机制。方法成年杂种犬14条,随机分为实验组8条,对照组6条。实验组首先测量左肺静脉和左心耳的有效不应期,继而刺激心房左后脂肪垫诱发房颤。消融Marshall韧带上段后和下段后重复上述步骤。对照组除不干预Marshall韧带外,其它电刺激方案与实验组相同,同时对该组犬的心脏进行迷走神经染色。结果①实验组消融Marshall韧带后,左肺静脉和左心耳的有效不应期均显著延长(P0.05)。②和消融前比较,实验组消融Marshall韧带上段后的房颤诱发率有下降趋势(70.8%vs87.5%,P0.05);消融Marshall韧带全程后房颤诱发率显著下降(33.3%,P0.001)。对照组三次电刺激所测得的不应期和房颤诱发率无差异。③Marshall韧带与左下肺静脉、心房左后脂肪垫、左心耳之间存在迷走神经的直接联系。结论消融犬Marshall韧带可显著降低刺激心房左后脂肪垫所致房颤的诱发率。     

低强度自主神经节刺激对心房电生理特性的影响

目的研究6h低强度自主神经节（GP）刺激对犬心房电生理性质的影响。方法22只成年杂种犬开胸暴露心脏,在左右心房、左右心耳及肺静脉缝置多极电极导管用以记录和刺激。实验组16只犬同时在左上GP及右前GP予以6h低强度高频刺激（0．1—1．0V）,使心率下降10％。对照组6只犬在心房远离GP处给于同样6h低强度刺激（无心房激动）。刺激前、刺激开始时及6h刺激后测定各部位有效不应期（ERP）及心房颤动（房颤）易颤窗口（WOV）。结果在实验组犬中,GP刺激开始时ERP及WOV较刺激前差异均无统计学意义,GP刺激6h后各部位ERP均显著缩短,总WOV显著增加（127＋35对0对0,P〈O．05）。对照组中,刺激前、刺激开始时及刺激6h后ERP及WOV（3±2对0对0,P〉0．05）差异均无统计学意义。结论6h低强度GP刺激可致心房电生理性质显著改变,并有利于房颤发生,提示长期低强度自主神经系统激活可形成有利于房颤发生的电生理基质。