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。     

短期房颤对兔肺静脉心肌细胞有效不应期及L型钙电流的影响

目的研究在短期快速肺静脉起搏下,易诱发房颤（AF）的兔肺静脉心肌细胞有无急性电重构改变。方法建立兔肺静脉源性AF的动物模型,应用程序刺激的方法测定和计算肺静脉远、近两端的有效不应期之差（ΔERP）;并通过全细胞膜片钳技术记录钙离子流变化。结果在同样刺激条件下,不是所有实验动物均可诱发出AF。快速肺静脉起搏和AF时均引起肺静脉远、近两端心肌细胞ERP之差值（ΔERP）减小,同时在AF持续过程中还可引起钙电流减小。结论通过短期快速肺静脉刺激,发现易触发AF的肺静脉在AF发生和持续时,其肺静脉心肌细胞有急性电重构的存在,L型钙电流减小可能是短期AF导致肺静脉心肌细胞发生急性电重构的离子基础之一。     

快速刺激及药物对犬肺静脉电重构的影响研究

目的研究快速刺激及药物（维拉帕米、阿托品）刺激对犬肺静脉电重构的影响,探讨肺静脉对心房颤动（房颤）的发生及维持的作用。方法测量快速刺激及药物（维拉帕米、阿托品）刺激犬肺静脉时肺静脉有效不应期、有效不应期频率适应性、房颤诱发率和持续时间。结果①与刺激前比较．快速刺激时肺静脉有效不应期及有效不应期频率适应性在刺激后即刻、5min有显著性差异．刺激后10min时无明显差异;刺激前、后肺静脉的房颤诱发率及房颤持续时间有显著性差异。②维拉帕米、阿托品使肺静脉有效不应期缩短及有效不应期频率适应性下降。结论快速刺激犬肺静脉可以导致肺静脉发生急性电重构．但可在短时间内恢复。在犬的试验中维拉帕米、阿托品可改变肺静脉发生电重构的程度,并加快肺静脉有效不应期频率适应性恢复速度。     

快速刺激及药物对犬肺静脉电重构的影响研究

目的 研究快速刺激及药物(维拉帕米、阿托品)刺激对犬肺静脉电重构的影响,探讨肺静脉对心房颤动(房颤)的发生及维持的作用.方法 测量快速刺激及药物(维拉帕米、阿托品)刺激犬肺静脉时肺静脉有效不应期、有效不应期频率适应性、房颤诱发率和持续时间.结果 ①与刺激前比较,快速刺激时肺静脉有效不应期及有效不应期频率适应性在刺激后即刻、5 min有显著性差异,刺激后10 min时无明显差异;刺激前、后肺静脉的房颤诱发率及房颤持续时间有显著性差异.②维拉帕米、阿托品使肺静脉有效不应期缩短及有效不应期频率适应性下降.结论 快速刺激犬肺静脉可以导致肺静脉发生急性电重构,但可在短时间内恢复.在犬的试验中维拉帕米、阿托品可改变肺静脉发生电重构的程度.并加快肺静脉有效不应期频率适应性恢复速度.     

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。     

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。     

快速心房电刺激对人心房不应期的影响及卡托普利的干预作用

探讨快速心房电刺激对人心房有效不应期 (AERP)的影响及卡托普利的干预作用。选择本院行射频消融术的 38例成年患者为研究对象 ,随机分为卡托普利组 (14例 )、维拉帕米组 (12例 )及生理盐水对照组 (12例 )。分别在阻断心脏自主神经后 ,观察各组用药前、后及快速心房刺激后AERP的变化及AF诱发情况。结果 :①快速心房刺激可使 5 7.9%成人正常心脏诱发AF ;②诱发AF后AERP明显缩短 ,而未诱发AF者的AERP无明显变化 ;③卡托普利及维拉帕米均能显著延长诱发AF患者的AERP ;④卡托普利能减少AF诱发率 ,并缩短AF持续时间 ;而维拉帕米则使AF诱发率增加、持续时间延长。结论 :①快速心房刺激可使部分患者AERP缩短 ,并诱发这类患者发生AF ;②卡托普利可显著延长诱发AF患者的AERP ,并使AF诱发率降低、持续时间缩短     

外源性与内源性自主神经刺激对心房颤动诱发性的影响

目的探讨心脏外源性与内源性自主神经刺激对心房颤动(房颤)诱发性的影响。方法16只成年犬静脉麻醉后,分离右颈迷走神经干(VST);再行右侧开胸手术,暴露靠近右上肺静脉的心脏脂肪垫(内含心脏自主神经丛,即GP),将1根电极导管固定贴靠于右上肺静脉,使其头端电极贴靠右上肺静脉与左房交界处,进行程序期前刺激,采用2倍、4倍、10倍阈值的刺激强度进行基础程序期前刺激(control),并测量相应的心房不应期(ARP)及房颤诱发窗宽(WOV);再分别加用VST刺激或GP刺激,测量在相应刺激条件下程序期前刺激所获得的ARP及WOV。结果平均基础心率(HR)为153±22次/min,VST刺激下HR为79±44次/min,GP刺激下HR为87±99次/min(后二者比较,P>0·05)。最短的ARP在control状态下为101±20ms、VST刺激下为90±17ms、GP刺激下为91±13ms,VST刺激下及GP刺激下均较control明显缩短(P<0·05),VST刺激下与GP刺激下的差异无统计学意义(P>0·05)。三者的累计WOV分别为control22±34ms、VST刺激下44±45ms、GP刺激下99±75ms,三者间每两者的差异均有统计学意义(P<0·05)。结论在降低心率相近的情况下,电刺激心脏内源性自主神经丛与电刺激心脏外源性自主神经引起的不应期缩短相近,但前者更容易诱发房颤。     

不同部位刺激诱发心房颤动时碎裂电位的出现与分布

目的 探讨在心房和肺静脉不同部位行电刺激诱发心房颤动（简称房颤）时碎裂电位（CFAEs）的出现与分布。方法 22只成年健康杂种犬,常规麻醉,气管插管,切断双侧颈迷走神经干,破坏颈交感神经节,建立动物的去自主神经模型。双侧开胸,分别在右心耳、左心耳和四支肺静脉的近、中、远段行电刺激诱发房颤,观察在基础刺激、双侧强迷走刺激两种诱发条件下,房颤发作时CFAEs的分布情况。结果 刺激诱发房颤的部位与CFAEs出现的部位并不完全一致。双侧心房（心耳）及肺静脉口附近是房颤时CFAEs出现的高频部位。当伴有迷走神经刺激时,房颤的诱发率提高,CFAEs的出现频率也随之明显增加。结论 房颤时CFAEs的分布并不局限于心房或肺静脉的某一局部区域,而是在多个部位可同时标测到。迷走刺激条件下标测到CFAEs的频率增加。     

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.     

自主神经干预对心房恢复性质的影响

目的 研究心脏自主神经干预对心房恢复性质的影响.方法 正常成年杂种犬10只,开胸后将多极电生理导管缝置于肺静脉、左右心耳和左右心房处,应用Ag-AgCl电极记录标测部位单相动作电位,在基础状态和颈部迷走神经刺激条件下构建标测部位恢复曲线,分别对标测部位进行快速电刺激,记录心房颤动（房颤）诱发时的起搏周长和持续时间.心脏自主神经节（GP）消融后重复上述步骤.结果 GP消融前迷走神经刺激同基础状态相比显著缩短动作电位时限（APD）,降低恢复曲线最大斜率（Smax）,抑制APD电交替,但房颤容易发生（P＜0.05）.GP消融后,APD较消融前显著延长,恢复曲线Smax增大,APD电交替提前,但房颤不易诱发（P＜0.05）;GP消融后迷走神经刺激效应明显减弱.GP消融前迷走神经刺激能显著增加APD恢复曲线Smax离散度（0.5±0.2对0.3±0.1,P＜0.05）,而GP消融能显著降低APD恢复曲线Smax离散度（0.2±0.1对0.3±0.1,P＜0.05）.结论 恢复曲线的斜率并不能完全解释房颤的诱发和维持,心房APD电交替可能对房颤的诱发并无预测作用,恢复性质的离散可能是诱发房颤的重要因素.     

Acute electrophysiological modulation of the atria and pulmonary veins: effects of sympathetic and parasympathetic interaction on atrial fibrillation inducibility

Atrial fibrillation (AF) is a complex disease with multiple mechanisms, involving the interaction between the autonomic nervous system (ANS), electrophysiological properties of the atria and pulmonary veins (PVs), and vulnerability for AF.AimWe assessed the effects of acute vagal (vagus_stim) and sympathetic stimulation (symp_stim) on atrial conduction, atrial and PV refractoriness and inducibility of AF in an in vivo rabbit model with preserved autonomic innervation.MethodsAn open-epicardial approach was used in 17 anesthetized and artificially ventilated New Zealand white rabbits. The ECG was recorded with bipolar subcutaneous electrodes placed in the four limbs. Electrograms were obtained with four monopolar electrodes placed epicardially along the atria, and a circular electrode adapted to the proximal PVs. The cervical vagus nerve and thoracic sympathetic trunk were stimulated with bipolar electrodes. Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs) and conduction times from the high-lateral right atrium (RA) to the high-lateral left atrium (LA) and PVs were quantified at baseline and during vagus_stim, symp_stim, or combined vagal and sympathetic stimulation (dual_stim). Burst pacing (50 Hz, 10 s), alone or combined with vagus_stim, symp_stim or dual_stim, was performed in the right (RAA) and left atrial appendage (LAA) and PVs to test for AF inducibility.ResultsAt baseline, ERPs were higher in the LAA and there was a delay in the conduction time from RA to PV, compared to the mean activation time from RA to LA. During vagus_stim or dual_stim, ERP decreased significantly at all sites, and baseline interatrial activation times changed from 20 ± 4 ms to 30 ± 10 ms and 31 ± 11 ms, respectively (p<0.05). Symp_stim resulted in a significant decrease in ERPs only in the LAA, and a reduction of the interatrial interval to 16 ± 11 ms (p<0.05 vs baseline). AF inducibility ranged from 35% to 53% with baseline 50 Hz pacing, 65% to 76% during vagus_stim or symp_stim, and 75% to 100% with dual_stim (p<0.05). AF duration increased significantly during ANS stimulation. In two-thirds of the animals with longer inducible AF, the arrhythmia ceased immediately after cessation of vagus_stim.ConclusionsIn the fully innervated rabbit heart in vivo, acute ANS stimulation shortens atrial and PV refractoriness, and significantly changes atrial conduction times, promoting AF induction and prolonging the arrhythmia. This underscores the importance of acute variations in ANS tone and its interactions in the pathophysiology of AF.     

Focal atrial fibrillation: experimental evidence for a pathophysiologic role of the autonomic nervous system

INTRODUCTION: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. METHODS AND RESULTS: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing high-frequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13+/-8 V and AT/AF at 15+/-9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19+/-6 V and AT/AF at 26+/-6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89+/-35 msec to 60+/-22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolar-izations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. CONCLUSION: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation.     

Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia

Intrinsic Cardiac Ganglia Activity Inhibited by Low‐Level Vagal Stimulation . Introduction: We hypothesized that low‐level vagosympathetic stimulation (LL‐VNS) can suppress atrial fibrillation (AF) by inhibiting the activity of the intrinsic cardiac autonomic nervous system (ICANS). Methods and Results: Wire electrodes inserted into both vagosympathetic trunks allowed LL‐VNS at 10% or 50% below the voltage required to slow the sinus rate or atrioventricular conduction. Multielectrode catheters were attached to atria, atrial appendages and all pulmonary veins. Electrical stimulation at the anterior right and superior left ganglionated plexi (ARGP, SLGP) was used to simulate a hyperactive state of the ICANS. Effective refractory period (ERP) and window of vulnerability (WOV) for AF were determined at baseline and during ARGP+SLGP stimulation in the presence or absence of LL‐VNS. Neural activity was recorded from the ARGP or SLGP. ARGP+SLGP stimulation induced shortening of ERP, increase of ERP dispersion and increase of AF inducibility (WOV), all of which were suppressed by LL‐VNS (10% or 50% below threshold) at all tested sites. Sham LL‐VNS failed to induce these changes. The effects of LL‐VNS were mediated by inhibition of the ICANS, as evidenced by (1) LL‐VNS suppression of the ability of the ARGP stimulation to slow the sinus rate, (2) the frequency and amplitude of the neural activity recorded from the ARGP or SLGP was markedly suppressed by LL‐VNS, and (3) the spatial gradient of the ERP and WOV from the PV‐atrial junction toward the atrial appendage was eliminated by LL‐VNS. Conclusions: LL‐VNS suppressed AF inducibility by inhibiting the neural activity of major GP within the ICANS. (J Cardiovasc Electrophysiol, Vol. 22, pp. 455‐463)     

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.     

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。     

Unique autonomic profile of the pulmonary veins and posterior left atrium.

OBJECTIVES: The purpose of this study was to investigate the electrophysiologic profile of the pulmonary veins (PVs) and left atrium (LA) in response to autonomic manipulation. BACKGROUND: The parasympathetic innervation of the PVs and posterior left atrium (PLA) is thought to contribute to focal atrial fibrillation (AF). We hypothesized that autonomic effects would be more prominent in these regions. METHODS: In 14 dogs, epicardial mapping was performed in the PVs, PLA, and left atrial appendage (LAA) under the following conditions: baseline, 20-Hz cervical vagal stimulation (VS), propranolol (P), P + VS, and P + atropine. Effective refractory periods (ERPs) were measured, and conduction vectors were computed at multiple sites. Western blotting and immunostaining were performed for IKAch (Kir3.1/3.4). RESULTS: The VS and P + VS caused more ERP shortening in the PV and PLA than in the LAA. The P + atropine caused greatest ERP prolongation in the LAA. Cumulative ERP change (ERP difference between P + VS and P + atropine) was greatest in the LAA and corresponded with expression of Kir3.1/3.4 (LAA > PLA > or = PV). The ERP change in response to vagal manipulation was most heterogeneous in the PLA; this corresponded with a pronounced heterogeneity of Kir3.1 distribution in the PLA. With VS and/or P, there was evidence of regional conduction delay in the PVs with a significant change in activation direction. Similar activation changes were not seen in the PLA and LAA. CONCLUSIONS: The PVs and PLA demonstrate unique activation and repolarization characteristics in response to autonomic manipulation. The heterogeneity of vagal responses correlates with the pattern of IKAch distribution in the LA. The peculiar autonomic characteristics of the PVs and PLA might create substrate for re-entry and AF.     

Autonomically induced conversion of pulmonary vein focal firing into atrial fibrillation

OBJECTIVES: This study was designed to determine the mechanism(s) whereby focal firing from pulmonary veins (PVs) is converted into atrial fibrillation (AF). BACKGROUND: The mechanism(s) whereby PV focal firing or even a single PV depolarization is converted into AF is unknown. METHODS: In 14 anesthetized dogs a right thoracotomy was performed to expose the right superior pulmonary vein (RSPV). An octapolar electrode catheter was sutured alongside the RSPV so that the distal electrode pair was adjacent to the fat pad containing autonomic ganglia (AG) at the veno-left atrial (LA) junction. An acrylic plaque electrode on the fat pad allowed AG stimulation at voltages ranging from 0.6 to 4.0 V. Multi-electrode catheters were sutured to the atria with their distal electrode pairs at the fat pad-atrial junctions. Right superior pulmonary vein focal firing consisted of S(1)-S(1) = 330 ms followed by as many as 11 atrial premature depolarizations (APDs) (A(2)-A(12)) whose coupling interval just exceeded RSPV refractoriness. RESULTS: Autonomic ganglia stimulation, without atrial excitation, caused a reduction in heart rate (HR): control 142 +/- 15/min, 4.0 V; 75 +/- 30/min, p /=9.3 V. CONCLUSIONS: The effects of AG stimulation at the base of the RSPV can provide a substrate for the conversion of PV firing into AF.