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。     

Vagal denervation and atrial fibrillation inducibility: Epicardial fat pad ablation does not have long-term effects

BACKGROUND: Major epicardial fat pads contain cardiac ganglionated plexi of the autonomic, predominantly vagal nerves. Vagal denervation may improve the success rate of atrial fibrillation (AF) treatment. OBJECTIVES: The purpose of this study was to elucidate the long-term effects of fat pad ablation on the electrophysiologic characteristics of the atrium and AF inducibility. METHODS: Six mongrel dogs were studied. Cervical vagal stimulation was applied to determine effects on the sinus node, AV node, atrial effective refractory period (AERP), and AF inducibility. AERP and AF inducibility were evaluated at both the right atrial and left atrial appendages and at the right atrial and left atrial free walls. Radiofrequency energy was delivered epicardially to the entire areas of two major fat pads: right pulmonary vein fat pad and inferior vena cava-left atrium fat pad. Cervical vagal stimulation then was applied to confirm the acute effects of fat pad ablation. The same evaluation was repeated 4 weeks later. RESULTS: The effects of vagal stimulation on the sinus node, AV node, and AERP were significantly eliminated immediately after fat pad ablation. However, these denervation effects disappeared after 4 weeks. At baseline, AF inducibility was increased by vagal stimulation (right atrial appendage: 72% +/- 31% vs 4.8% +/- 12%; right atrial free wall: 75% +/- 31% vs 0.0% +/- 0.0%; left atrial appendage: 60% +/- 29% vs 0.0% +/- 0.0%; left atrial free wall: 65% +/- 42% vs 0.0% +/- 0.0%). Fat pad ablation significantly reduced this vagal stimulation effect (8.3% +/- 20%, 10% +/- 22%, 17% +/- 29%, and 25% +/- 29%, respectively). However, similar to baseline, AF inducibility was strongly augmented by vagal stimulation 4 weeks after fat pad ablation (96% +/- 10%, 100% +/- 0.0%, 100% +/- 0.0%, and 95% +/- 11%, respectively). CONCLUSION: Radiofrequency fat pad ablation may not achieve long-term suppression of AF induction in this canine model.     

Mechanism for Pituitary Adenylate Cyclase-Activating Polypeptide-Induced Atrial Fibrillation

INTRODUCTION: Pituitary adenylate cyclase-activating polypeptide (PACAP), which activates intracardiac postganglionic parasympathetic nerves, has a greater profibrillatory effect than vagal stimulation. However, the mechanism responsible for this is unclear. METHODS AND RESULTS: We examined the effective refractory period (ERP), conduction time, and incidence of atrial fibrillation (AF) induced by a single premature extrastimulus at four atrial sites as well as the AF cycle length at 65 atrial sites in 12 autonomically decentralized, open chest, anesthetized dogs. These parameters were measured in the control condition, during cervical vagal stimulation, and after PACAP administration. PACAP shortened the ERP to a similar extent at all four sites. Vagal stimulation shortened the ERP primarily at the high right atrium, but not at the other three sites. Global dispersion of ERP and variation in the AF cycle length (P < 0.01) were less after PACAP than during vagal stimulation. A premature extrastimulus induced AF more frequently after PACAP than during vagal stimulation (P < 0.001). The ERP at the pacing site was shorter when AF was induced than when it was not induced regardless of the intervention and the pacing site. Conduction time following premature beats that induced AF was shorter after PACAP than during vagal stimulation (P < 0.01). CONCLUSION: Global ERP shortening contributes to the greater profibrillatory effect of PACAP. In addition, the decreased conduction time following premature beats may be associated with AF induction in this model.     

射频消融第三脂肪垫对犬心房电生理参数及心房颤动诱发的影响

目的研究射频消融第三脂肪垫对犬心房电生理参数及心房颤动(房颤)诱发的影响。方法观察12只杂种犬在不同起搏周长下,消融第三脂肪垫前后心房不同部位有效不应期(AERP)、AERP离散度、AERP频率适应性,房颤诱发率及其诱发窗口的变化。结果与消融前相比,消融后心率变化差异无统计学意义(P>0.05)。随着起搏周长变短,AERP明显缩短,且差异具有统计学意义(均为P<0.05)。消融术后高位左心房、低位左心房、左心耳部位AERP明显缩短,高位右心房、低位右心房、右心耳部位AERP明显延长(均为P<0.05)。AERP离散度差异无统计学意义(P>0.05)。消融后不同测量部位的房颤诱发率均降低及房颤诱发窗口增宽。结论消融第三脂肪垫达到部分去迷走神经化,使左心房AERP缩短,同时使房颤诱发率降低及房颤诱发窗口增宽。     

房室结慢径区域消融对迷走神经功能及心房颤动易感性的影响

目的心房颤动（房颤）与房室结折返性心动过速有着某种程度的关联性,慢径区域消融可能影响了心房自主神经功能而导致窦性心动过速。但慢径区消融对心房自主神经功能的具体影响目前尚不清楚。本文旨在探讨慢径区消融对心房迷走神经调节功能及房颤易感性的影响。方法11条成年杂种犬,全身麻醉下行颈交感一迷走神经干剥离术。经右颈内静脉穿刺放置冠状静脉窦导管,经左股静脉穿刺放置右心室导管及右心房标测电极导管（Halo导管）,经右股静脉穿刺放置消融导管和希氏束导管。静脉应用美托洛尔阻断交感神经活性。测量慢径区域消融前后基础状态及迷走神经刺激下的窦性周长（SCL）及高位右心房（HRA）、低位右心房（IRA）、冠状静脉窦近端（CSp）和冠状静脉窦远端（CSd）的有效不应期（ERP）及心房易感窗口（VW）。结果（1）SCL的变化：消融前后迷走神经刺激导致的SCL缩短值无明显改变[（107±19）次／min对（108±8）次／min,P〉0．05],提示慢径区域消融没有明显改变迷走神经对窦房结的调节作用。（2）ERP的变化：消融前后迷走神经刺激导致的ERP缩短值在HRA分别为[（69±37）ms对（55±34）ms,P〉0．05],CSd分别为[（55±30）ms对（42±32）ms,P=0．08],IRA分别为[（66±24）ms对（19±21）ms,P〈0．001],CSp分别为[（46±24）ms对（7±18）ms,P〈0．001]。提示慢径区域消融对HRA及窦房结区域的迷走神经调节功能无明显影响,对CSd区域的迷走神经调节功能有一定的影响,而导致了IRA及CSp区域去迷走神经效应。（3）心房VW的变化：消融前后基础状态下各个部位刺激均较难诱发房颤（VW接近0）。消融后,HRA迷走神经刺激诱发房颤的能力较消融前没有明显变化[（63±31）ms对（63±25）ms,P〉0．05],CSd的VW有一定程度的降低[（35±37）ms对（57±28）ms,P     

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.     

Heart rate turbulence after atrial premature beats before spontaneous onset of atrial fibrillation

OBJECTIVES: This study was designed to assess the temporal changes in vagal responses to atrial premature beats before spontaneous onset of atrial fibrillation (AF). BACKGROUND: Enhanced vagal activity plays a major role in the onset and perpetuation of experimental AF, but the role of vagal activation in the onset of clinical AF episodes is not so well established. METHODS: We calculated heart rate turbulence after atrial premature impulses occurring 0 to 60 min before the onset of AF ("prior to AF") and compared it with the hourly means of the other hours of the 24-h electrocardiogram recordings ("non-AF hours") in 39 patients with structural heart disease and 29 patients with lone AF. Traditional heart rate variability measurements and approximate entropy (ApEn) were also analyzed. RESULTS: Turbulence onset (TO) was significantly less negative during the 1 h preceding AF than during the non-AF hours (0.71 +/- 1.76 vs. -0.35 +/- 1.46, p < 0.00001). Less negative TO before AF was observed among both the patients with structural heart disease (1.16 +/- 1.73 vs. 0.07 +/- 1.23; p < 0.0001) and those with lone AF (0.17 +/- 1.67 vs. -0.85 +/- 1.56; p < 0.0001). No significant difference was seen in the turbulence slope between the two periods, and none of the traditional frequency and time domain measurements differentiated between the periods; ApEn was significantly lower before AF than during the non-AF hours (p < 0.01). CONCLUSIONS: Altered heart rate dynamics, suggesting transient enhancement of vagal outflow after premature atrial excitation, are temporally related to spontaneous onset of clinical AF.     

选择性刺激犬心房窦房结脂肪垫的电生理观察

目的 位于右心房及右肺静脉交界处的窦房结(SAN)脂肪垫含有丰富的支配心房的副交感神经纤维节.本实验通过选择性直接刺激心脏SAN脂肪垫,观察其对SAN功能、房室传导、心房有效不应期(AERP)及心室有效不应期(VERP)、心房颤动(AF)诱发易感性等电生理参数的影响,以明确心房SAN脂肪垫的副交感神经功能分布特点及探讨AF发生机制.方法 入选杂种犬33只,右侧开胸暴露SAN脂肪垫.将标准的电生理导管置于右心房、希氏束、右心窒心尖部及右心室流出道,记录基础窦性周期长度(SCL)、AH及HV间期、房室结文氏点、AERP及VERP、AF诱发窗口(WOV)及快速右心房起搏诱发AF的RR间期.以逐级递增的能量直接刺激SAN脂肪垫直至AF诱发,测定不同能量状态下SCL及AF诱发阈值.以引起SCL较基线延长50%的固定能量再次刺激SAN脂肪垫,观察其对上述电生理参数的影响.AF诱发成功后,继续逐级增加刺激能量直至最人值10.0 mA.记录不同能量状态下诱发AF的连续10个RR间期,取其平均值.结果 100%犬在直接SAN脂肪垫刺激下诱发AF,AF诱发阈值为(4.0±1.3)mA.AF诱发前,SAN脂肪垫刺激导致窦性心率减慢[SCL:(588±77)ms对(994±293)ms,P<0.001].AF诱发后,直接刺激诱导AF RR间期进行性延长[(461±204)ms对最长(636±260)ms,P<0.001],个别犬出现高度房室阻滞.在以延艮SCL 50%的固定能量刺激SAN脂肪垫时,AERP与刺激前比较明显缩短(P<0.001)、WOV增宽(P<0.001),而AH、HV、房室结文氏点、VERP无变化(P>0.05).结论 直接SAN脂肪垫刺激延长SCL,缩短AERP,增加AF诱发易感性,而对房窒结下区传导及心室无影响.以前文献报道SAN脂肪垫只有单一调节SAN的功能,而本实验结果显示当刺激能量足够时,SAN脂肪垫还町减慢AF时房窜传导.     

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.     

单纯消融犬心外膜脂肪垫的远期心电生理效应

目的探讨系统消融犬心外膜脂肪垫（完全去迷走神经）的远期心电生理效应。方法成年雄性杂种犬16条,随机分为消融组和假手术组（各8条）。消融组犬经开胸途径消融心外膜所有可视脂肪垫,假手术组仅进行开胸手术。术后8周行心内电生理检查,测定右心房、左心房、左心室、右心室心尖部及右心室流出道等部位的不应期,并进行房性及室性快速心律失常的诱发。结果术后8周实验组基础心率（163．8±12．2）~／min显著高于假手术组对（122．7±13．0）次／min（P〈O．001）;消融组犬的右心房、左心房、左心室、右心室心尖部及右心室流出道不应期分别较假手术组显著缩短（除右心室心尖部P=0．012外,其他部位P〈O．001）,同时该组的快速房性心律失常诱发率显著增加（P=0．04）,两组间的室性快速心律失常诱发率差异无统计学意义。结论仅消融犬心外膜脂肪垫可能具有远期致心律失常作用,尤其在心房水平。     

窦房结脂肪垫对犬右上肺静脉电生理特性影响的研究

目的研究不同水平刺激窦房结脂肪垫(SANFP)对右房(RA)及右上肺静脉(RSPV)的有效不应期(ERP)及心房颤动(简称房颤)诱发率的影响,探讨SANFP对房颤发生维持的作用。方法6只犬麻醉后经右侧开胸暴露RSPV及SANFP,以0.6～2,5,8mV三种不同电压强度水平、60ms频率刺激SANFP,同时以S1S2刺激观察三种水平下RA游离壁远、中、近端及RSPV远、中、近端ERP的变化;同样方法刺激SANFP以S1S1和S1S2程序刺激诱发房颤,测定房颤的诱发率。结果以5mV电压刺激窦房结脂肪垫RSPV近端ERP较基础时明显缩短(90±24msvs109±16ms,P<0.05),其房颤诱发率50%;以5,8mV电压刺激SANFP时RA游离壁近端、中端ERP变化较基础时明显缩短(96±20msvs117±14ms,65±20msvs117±14ms,P均<0.05),其房颤诱发率100%。结论窦房结脂肪垫可能在肺静脉起源的房颤的诱发和维持中起了重要作用。     

Impact of pulmonary vein isolation on atrial vagal activity and atrial electrical remodeling

Objective Mechanisms of pulmonary vein isolation (PVI) for atrial fibrillation remain controversy.This study aimed to investigate the impact of PVI on vagal modulation to atria.Methods Eighteen adult mongrel dogs under general anesthesia were randomly divided into two groups.Bilateral cervical sympathovagal trunks were decentralized and sympathetic effects was blocked by metoprolol administration.Atrial electrical remodeling (AER) was established by rapid right atrial pacing at the rate of 600 bpm for 30 minutes.PVI was performed in group A.Atrial effective refractory period (ERP),vulnerability window (VW) of atrial fibrillation,and sinus rhythm cycle length (SCL) were measured at baseline and during vagal stimulation before and after atrial rapid pacing with and without PVI at fight atrial appendage (RAA),left atrial appendage (LAA),distal coronary sinus (CSd) and proximal coronary sinus (CSp).Results (1) Effects of PVI on vagal modulation:Shortening of SCL during vagal stimulation decreased significantly after PVI compared with that before PVI in group A (P＜0.001).Shortening of ERP during vagal stimulation decreaseed significantly after PVI compared with that before PVI (P＜0.05).VW of atrial fibrillation during vagal stimulation decreased significantly after PVI compared with that before PVI (P＜0.05).(2) Effects of PVI on AER:shortening of ERP before and after atrial rapid pacing increased significantly at baseline and vagal stimulation in group B compared with that in group A (P＜0.05).VW during vagal stimulation increased significantly after atrial rapid pacing in group B (P＜0.05).Conclusion PVI attenuates the vagal modulation to the atria,thereby decreases the susceptibility to atrial fibrillation mediated by vagal activity.PVI releases AER,which maybe contributes to the vagal denervation.Our study indicates that PVI not only can eradicate triggered foci but also modify substrates for AF.(J Geriatr Cardiol 2008;5:28-32)     

Effects of simultaneous atrioventricular pacing on atrial refractoriness and atrial fibrillation inducibility: role of atrial mechanoelectrical feedback

INTRODUCTION: The purpose of this study was to evaluate the effects of an acute increase in atrial pressure on refractoriness (mechanoelectrical feedback) and the vulnerability to atrial fibrillation (AF) and to investigate the effects of autonomic blockade and verapamil on mechanoelectrical feedback in humans. METHODS AND RESULTS: Right atrial pressure and effective refractory period (ERP) at the right atrial appendage (RAA) and high right atrial septum were measured during sinus rhythm, and during atrial and simultaneous AV pacing at a cycle length of 300 msec, either in the absence (n = 25) or presence (n = 22) of pharmacologic autonomic blockade. In another 15 patients, the protocol was performed before and after infusion of verapamil 0.15 mg/kg. In the absence of autonomic blockade, AV pacing resulted in a higher mean right atrial pressure (11.7 +/- 3.3 vs 4.3 +/- 3.0 mmHg, P < 0.001) and a shorter atrial RAA ERP (144 +/- 23 msec vs 161 +/- 21 msec; P < 0.001) compared with atrial pacing; AF was induced more often during AV pacing (87%) than during atrial pacing (20%) and was related directly to the right atrial pressure (r = 0.39, P = 0.004) and indirectly to the RAA ERP (r = -0.42, P < 0.001). The susceptibility to sustained AF was greatly enhanced by autonomic blockade. Verapamil markedly attenuated the shortening of ERP and the propensity for AF that occurred during simultaneous AV pacing. CONCLUSION: An acute increase in atrial pressure during tachycardia is associated with shortening of atrial refractoriness and a propensity for AF, i.e., atrial mechanoelectrical feedback, which may be enhanced by autonomic blockade and attenuated by calcium channel blockade.     

Atrial electrophysiological properties evaluated by right and left atrial pacing in patients with or without atrial fibrillation

Coronary sinus (CS) pacing has been shown to prevent induction of atrial fibrillation (AF) by suppression of the propensity of atrial premature beats at high right atrium (HRA) to induce local conduction delay at the posterior triangle of Koch. However, other mechanisms of CS pacing in preventing induction of AF have not been explored. This study investigated whether a differential conduction delay exists between the HRA and distal CS pacing in patients with paroxysmal AF but not in patients without AF. Nine patients with atrioventricular reentrant tachycardia utilizing a left accessory pathway undergoing catheter ablation were included in this study. Group 1 consisted of 5 patients with clinically documented paroxysmal AF and group 2 4 patients without a history of AF. The effective refractory periods (ERPs) of HRA, distal CS, and four different left atrial sites were determined. The interatrial conduction time and conduction delay between the HRA and distal CS during HRA or distal CS pacing were measured. The interatrial conduction delay (ICD) from the HRA to the distal CS during HRA pacing was significantly longer than that from the distal CS to the HRA during distal CS pacing in patients of group 1. However, the ICD from the HRA to the distal CS during HRA pacing was not significantly longer than that from the distal CS to the HRA during distal CS pacing in group 2 patients. A differential conduction delay between the HRA and the distal CS pacing is present in this specific population of patients with paroxysmal AF but not in patients without AF. The shorter conduction delay during DCS pacing may contribute to the prevention of induction of AF.     

Effects of sympathetic and parasympathetic stimulation on the induction of atrial flutter in dogs with aseptic pericarditis.

To study the effects of sympathetic stimulation (SS) and vagal stimulation (VS) on the induction of atrial flutter (AF) and its cycle length, aseptic pericarditis was produced surgically in 17 adult mongrel dogs. Programmed atrial stimulation was used to induce AF and to determine the effective refractory periods (ERP) and maximum conduction delay (maxCD) of the atrium. These tests were performed before and during stimulation of the right cervical vagus nerve and the right stellate ganglion. Results showed: (1) AF could be induced in animals with short ERP and large maxCD before SS; (2) ERP was significantly shortened, maxCD was significantly increased by VS; (3) During SS, ERP was slightly shortened, but there were no changes in maxCD and the induction rate of AF; (4) The cycle length of AF was shortened by SS, however, the cycle length of AF was shortened more notably by VS than by SS. From these findings, a shortening of the ERP and an increase in maxCD appear to be related to an increased AF induction rate by VS.     

Cellular mechanisms of vagally mediated atrial tachyarrhythmia in isolated arterially perfused canine right atria

INTRODUCTION: Increased vagal tone significantly enhances susceptibility to atrial fibrillation (AF); however, the cellular mechanisms responsible for vagally mediated AF are not completely understood. METHODS AND RESULTS: In 12 isolated arterially perfused canine right atria, high-resolution optical mapping techniques were used to measure action potentials during control conditions, during intracardiac parasympathetic nerve stimulation (IPS; 30 to 50 Hz) as a surrogate for vagal stimulation, and during acetylcholine (ACh) infusion (10 to 30 microM). During steady-state pacing, action potential duration was shorter during ACh infusion (43 +/- 9 msec) than during IPS (78 +/- 7 msec, P < 0.001) or control (129 +/- 5 msec, P < 0.001). In contrast, repolarization gradients were larger during IPS (13 +/- 3 msec/mm) than during ACh infusion (3 +/- 1 msec/mm, P < 0.01) or control (5 +/- 1 msec/mm, P < 0.01). Transmural repolarization gradients were relatively small for each intervention tested. During ACh infusion, atrial tachyarrhythmia (AT) was easily initiated with a single premature stimulus and was associated with a focal pattern of activation (84%). AT also was easily initiated by a single premature stimulus during IPS; however, when repolarization gradients were large, patterns of conduction block and incomplete macroreentry were often observed (64%). Importantly, AT initiation during IPS was associated with focal activity (36%) when repolarization gradients were small. CONCLUSION: In contrast to ACh infusion, IPS generally increased dispersion of repolarization and was often associated with patterns of conduction block and incomplete macroreentry, similar to that associated with in vivo cervical vagal stimulation. However, IPS also was associated with a focal pattern of initiation that was independent of local repolarization gradients. These results suggest that during vagal stimulation, AT initiation does not always depend on repolarization gradients.     

Electrophysiological abnormalities of the atrial muscle in patients with paroxysmal atrial fibrillation associated with hyperthyroidism

OBJECTIVE: Atrial fibrillation (AF) is common in patients with hyperthyroidism. Although the choice of an antiarrhythmic agent should be based on its electrophysiological effects and the electrophysiological properties of the arrhythmia in question, the atrial electrophysiological features of AF associated with hyperthyroidism are unknown. The purposes of this study are to clarify the atrial electrophysiological abnormalities of AF with hyperthyroidism, and to propose effective therapies for AF in patients with hyperthyroidism. SUBJECTS AND DESIGN: This study included 117 patients who underwent electrophysiological study and were evaluated for thyroid function: 29 patients without AF or hyperthyroidism (Group I), 78 patients with lone paroxysmal AF (Group II), and 10 patients with paroxysmal AF and hyperthyroidism (Group III). The following electrophysiological parameters were assessed and measured quantitatively: (1) the incidence of abnormal right atrial electrograms during sinus rhythm, indicating areas of altered anatomy and conduction where AF is likely to develop; (2) the atrial effective refractory period (ERP); and (3) the atrial conduction delay (CD), which is induced by early atrial premature beats close to the atrial ERP and is thought to facilitate the occurrence of AF. RESULTS: The incidence of abnormal right atrial electrograms during sinus rhythm was significantly higher in Group II (67.1%) than in Group I (20.0%, P < 0.001) and Group III (22.2%, P = 0.009). The atrial ERP was significantly shorter in Group III (187 +/- 7 ms) than in Group I (215 +/- 36 ms, P = 0.019) and Group II (208 +/- 28 ms, P = 0.022). The atrial CD was observed in Group III as well as in Group II. CONCLUSIONS: Our data indicate that the electrophysiological features of paroxysmal AF associated with hyperthyroidism are essentially different from those of lone paroxysmal AF. In patients with paroxysmal AF and hyperthyroidism, a shortening of the refractory period in association with a facilitation of the atrial CD could be expected to increase the propensity for AF, and a pre-existent arrhythmogenic substrate might not be essential to the genesis of AF. These findings suggest that the agents that prolong the atrial ERP are effective against AF in patients with hyperthyroidism.     

Effects of pulmonary vein ablation on regional atrial vagal innervation and vulnerability to atrial fibrillation in dogs

INTRODUCTION: Pulmonary vein (PV) isolation has proven to be an effective therapy for atrial fibrillation (AF). However, clinical evidence suggests that suppression of AF after PV isolation could not be fully attributed to the interruption of electrical conduction in and out of the PVs. Furthermore, little is known regarding the effects of ablation around the PVs on the atrial electrophysiological properties. We aimed to study the changes in atrial response to vagal stimulation (VS) after PV ablation (PVA). METHODS: We studied 11 adult mongrel dogs under general anesthesia. Bilateral cervical sympathovagal trunks were decentralized. Propranolol was given to block sympathetic effects. Multipolar catheters were placed into right atrial appendage (RAA), distal and proximal coronary sinus (CSD, CSP), and left atrial free wall (LAFW). PVA was performed via trans-septal approach. Atrial effective refractory period (AERP) and vulnerability window (VW) of AF were measured with and without VS before and after ablation to isolate the PVs. RESULTS: After ablation, AERP shortening in response to VS significantly decreased in the left atrium (43.64 +/- 21.57 vs 11.82 +/- 9.82 msec, P < 0.001 at LAFW; 50.91 +/- 26.25 vs 11.82 +/- 14.01 msec, P < 0.001 at CSP; 50 +/- 31.94 vs 17.27 +/- 20.54 msec, P < 0.005 at CSD), while the response to VS did not change significantly at RAA (58.18 +/- 28.22 vs 50.91 +/- 22.12 msec, P = 0.245). After ablation, atrial fibrillation VW during VS narrowed (20.63 +/- 11.48 vs 5.63 +/- 8.63 msec, P < 0.03 at LAFW; 26.25 +/- 12.46 vs 5.00 +/- 9.64 msec, P = 0.001 at CSP; 28.75 +/- 18.47 vs 6.88 +/- 7.53 msec, P < 0.02 at CSD, and 33.75 +/- 24.5 vs 16.25 +/- 9.91 msec, P = 0.03 at RAA). CONCLUSIONS: Ablation around the PV ostia diminishes left atrial response to VS and decreases the atrial VW. The attenuated vagal response after ablation may contribute to the suppression of AF.     

Limited benefit of septal pre-excitation in pace prevention of atrial fibrillation

BACKGROUND: Pre-excitation of the intra-atrial septum (IAS) by pacing at the ostium of the coronary sinus (CSO) can prevent atrial fibrillation (AF) in case of single atrial premature beats (APBs). We investigated whether pre-excitation of IAS, either by pacing at CSO or at the right ventricle in the presence of retrograde conduction (RV), can prevent atrial tachyarrhythmia triggered by single and multiple APBs. AF vulnerability was compared to pacing at the right atrium (RA) and sinus rhythm (SR). METHODS: Seventeen patients, age 52 +/- 21 years, who exhibited retrograde VA conduction and reproducible induction of atrial tachyarrhythmia during an electrophysiological procedure, were studied. Both during SR and pacing (S1-S1:600 ms) at RA, CSO, and right ventricle (RV), single (A1-S2:200 ms) and multiple premature stimuli (A1-S2-S3-S4:200-180-180 ms) were delivered at RA (4 x diastolic threshold). RESULTS: During pacing at RA, single and multiple APBs invariably induced runs of atrial tachyarrhythmia (mean duration 34 +/- 67 sec and 37 +/- 69 sec, range 1 sec to 20 min). During preventive pacing at CSO and RV, single APBs (A1-S2:200 ms) did not induce atrial arrhythmia (0 +/- 0 sec, 0 +/- 0 sec, P < 0.05 vs pacing at RA). In contrast, when multiple APBs were applied, pacing at CSO or RV failed to prevent initiation of AF (mean duration 36 +/- 63 sec, 38 +/- 65 sec, NS). Also during SR, single APBs did not induce AF (0 +/- 0 sec, P < 0.05 vs pacing at RA) whereas multiple APBs invariably induced AF (39 +/- 74 sec, NS). CONCLUSIONS: Compared to pacing at RA, pre-excitation of IAS either by pacing at CSO or at RV with retrograde conduction can prevent initiation of paroxysms of atrial tachyarrhythmia triggered by single but not by multiple right APBs. These findings imply that the potential benefit of choosing an optimal pacing site in patients requiring atrial-based pacing is limited. Moreover, in the absence of bradycardia, no specific pacing site offers incremental benefit over the natural "protective" effect of sinus rhythm.     

Electrophysiologic characteristics of the atrium in sinus node dysfunction: atrial refractoriness and conduction

INTRODUCTION: Clinical electrophysiology (EP) has focused attention on the EP properties of atrial muscle in patients with atrial fibrillation (AF). Patients with sinus node dysfunction (SND) sometimes are included in these studies, but the characteristics of these patients with SND alone appear less well investigated. METHODS AND RESULTS: We reviewed EP data of 46 patients (mean age 70 +/- 8 years) with SND, who underwent EP study for evaluation of the atrial substrate. In 16 patients, a history of paroxysmal AF was documented, but not in the remaining 30 patients who had SND alone. We considered as control a group of 25 subjects (mean age 63 +/- 14 years), who were referred to our EP laboratory for unexplained syncope or AV conduction disturbances. Following pharmacologic washout and at a drive cycle of 600 msec, effective (ERP) and functional refractory periods (FRP), S1-A1 and S2-A2 latency, A1 and A2 width, latent vulnerability index (ERP/A2), and P wave duration on the surface ECG were measured. Intra-atrial conduction times were measured from the stimulus artifact by pacing the high right atrium (HRA), to the corresponding atriograms at the AV node (HRA-AVN), low lateral atrium (HRA-LLA), and low interatrial septum close to the coronary sinus ostium (HRA-CSO). Compared with the control group, SND patients did not show differences in ERP (238 +/- 26 msec vs 250 +/- 29 msec), FRP (274 +/- 25 msec vs 280 +/- 32 msec), S1-A1 (38 +/- 15 msec vs 33 +/- 11 msec) and S2-A2 latency (67 +/- 24 msec vs 63 +/- 25 msec), or HRA-AVN (81 +/- 24 msec vs 65 +/- 19 msec), HRA-LLA (36 +/- 30 msec vs 40 +/- 27 msec), and HRA-CSO (77 +/- 17 msec vs 80 +/- 15 msec) conduction times. In contrast, we observed strong differences in atriogram durations A1 (59 +/- 19 msec vs 39 +/- 13 msec; P < 0.001) and A2 (92 +/- 28 msec vs 57 +/- 18 msec; P < 0.001), as well as in the latent vulnerability index ERP/A2 (2.8 +/- 1.2 msec vs 4.8 +/- 1.7; P < 0.001). Also, the P wave was slightly longer (104 +/- 18 msec vs 94 +/- 45 msec; P < 0.05). No significant statistical difference in EP parameters was found between SND patients with or without documented AF. CONCLUSION: In patients with SND, atrial refractoriness appears similar to that of control subjects. The most important EP abnormality appears to be local conduction slowing disturbances, with prolonged basal and postextrastimuli atriograms, responsible for a lower vulnerability index. This could explain, at least in part, the tendency of patients with SND to develop AF during their natural history. Normality of atrial refractoriness, in contrast to atrial conduction disorders, might explain why atrial pacing shows a preventative effect on the development of AF and why antiarrhythmic drugs often are ineffective.