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。     

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。     

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。     

射频消融心外膜脂肪垫治疗犬肺静脉左房交界处起源的心房颤动

目的探讨射频消融心外膜脂肪垫对左房-肺静脉交界触发的局灶性心房颤动(简称房颤)治疗的有效性。方法成年杂种犬10只,心外膜脂肪垫注射氯化乙酰胆碱(Ach)+左房短阵快速电刺激诱发犬左房-肺静脉交界触发的局灶性房颤模型。4极电极分别缝置于左房、右房、左肺静脉与左房交界处,记录最快激动部位。直视下射频消融心外膜脂肪垫。于房颤模型建立前后,及消融脂肪垫后测量左、右房有效不应期(ERP),肺静脉-左房交界处ERP、计算房颤诱发率。术毕处死实验犬行组织学检查。结果所有犬均能通过脂肪垫注射氯化Ach+左房短阵快速电刺激诱发出左房-肺静脉交界触发的局灶性房颤,建模后左房、右房、肺静脉-左房交界处的ERP均较建模前显著缩短(分别为94±33 ms vs 139±9 ms,104±17 ms vs 137±9 ms,104±17 ms vs 137±9 ms;P均<0.01)。脂肪垫消融后房颤诱发率与消融前比较显著降低(45%±16%vs 86%±4%,P均<0.01);左房、右房ERP无变化,肺静脉-左房交界处不应期显著延长(137±8 ms vs 104±17 ms,P<0.01)。组织学未发现除脂肪垫外的其它消融损伤灶。结论射频消融心外膜脂肪垫对肺静脉-左房交界触发的局灶性房颤治疗有效。     

心脏脂肪垫在肺静脉引发房颤中的作用

目的探讨窦房结-心房脂肪垫(SAFP)在右上肺静脉灶性放电引发阵发性房颤(PAF)中的作用。方法12条新疆家养犬,苯巴比妥钠麻醉,经右侧开胸暴露右侧肺静脉。将1根8极标测电极导管固定在右上肺静脉,给予S1S1600bpm起搏刺激,另将1根8极(1.5×1.5cm)电极板固定在心外膜窦房结-心房脂肪垫上。术中监测II和aVR导联、血压和体温。以1～4V电压、1000bpm频率刺激窦房结-心房脂肪垫30～60s。结果12条家养犬在给予S1S11000ppm窦房结-心房脂肪垫刺激,随着电压从1增加到4V,心率从142±20bpm减少到75±30bpm(p<0.05),同时出现房性早搏、房性心动过速(房速)和房颤,同时予以右上肺静脉S1S1600ppm刺激,诱发房颤的房性早搏数随着刺激电压1～4V的增加从7个减少到2个,并以S1S1300ms,S1S2稍长于右上肺静脉不应期的早搏右上肺静脉刺激。S1S1600ppm刺激下房颤诱发率从基础状态的49.86%提高到70.59%,S1S2早搏刺激下从3.78%提高到16.6%(p<0.05)。7条狗在4%利多卡因4ml注射到窦房结-心房脂肪垫局部阻滞神经后,6条狗在同样右上肺静脉刺激诱发房颤电压的条件下不能诱发房颤,其中3条狗在电压增加大于9V时诱发房颤。房颤诱发的有效刺激部位在窦房结-心房脂肪垫2～3mm的范围内。结论有效部位窦房结-心房脂肪垫刺激,能够诱发慢频率依赖性阵发性房颤,刺激窦房结-心房脂肪垫增加右上肺静脉阵发性房颤的诱发率,局部神经阻滞降低或消除阵发性房颤的诱发.提示:增强窦房结-心房脂肪垫的自发神经放电,可能是临床右上肺静脉灶性放电转变成房颤的基础,消融窦房结-心房脂肪垫可能预防阵发性房颤的诱发。     

心外膜脂肪垫网络迷走神经干对窦房结和房室结功能的影响

目的 探讨心外膜窦房结脂肪垫(SAN-FP)和房室结脂肪垫(AVN-FP)网络迷走神经干调控心脏活动的主控区.方法 杂种犬18只,分为A组和B组,以不同电压分别刺激左右迷走神经干、SAN-FP和AVN-FP,测定窦性心率(SR)和AH间期,A组先消融SAN-FP,在刺激迷走神经干的情况下测定SR和AH间期,再联合消融SAN-FP和AVN-FP,B组则先消融AVN-FP,再联合消融AVN-FP和SAN-FP.结果 ①右侧迷走神经干刺激产生的迷走效应强于左侧(SR减慢75％对41％),SAN-FP刺激引起SR减慢的最大幅度为13％;②优先消融SAN-FP后刺激迷走引起SR减慢的效应显著减弱,AH间期显著延长,联合消融后刺激迷走对SR的影响与消融前差异无统计学意义,但AH间期较消融前和单独消融时均显著延长;③优先消融AVN-FP刺激迷走引起SR减慢效应较消融前差异无统计学意义,AH间期较消融前明显延长,联合消融后刺激迷走对SR和AH间期的影响较单独消融时差异无统计学意义.结论 迷走神经干刺激的迷走效应右侧大于左侧,右侧迷走神经干主要通过AVN-FP调控窦房结功能.心外膜脂肪垫是迷走神经干调控窦房结和房室结功能的重要环节,AVN-FP是主控区,SAN-FP为辅助区.     

心脏脂肪垫在肺静脉灶性放电引发心房颤动中的作用

探讨心脏脂肪垫在肺静脉灶性放电与心房颤动 (简称房颤 )中的作用。 14条狗麻醉后经右侧开胸暴露右侧肺静脉。将 8极电极标测导管缝在右上肺静脉用于起搏。另放一 8极电极导管固定在临近右肺静脉和左房交接处脂肪垫。术中监测ECG的II和aVR导联、血压和体温。以 0 .1ms刺激间期 ,2 0Hz刺激频率的直方波刺激脂肪垫的迷走神经丛 30～ 5 0s,随着电压从 1～ 4 .5V ,心率逐渐减少 (P <0 .0 5 ) ,同时出现房性早搏、房性心动过速和房颤。在刺激迷走神经丛的同时 ,以 2 0 0～ 80 0次 /分的频率刺激肺静脉 (对照组没有迷走神经丛刺激 )均能诱发房颤。在迷走神经丛刺激下 ,以S1S1330ms,S1S2 稍长于肺静脉不应期的配对间期刺激肺静脉诱发房颤。与对照组比较 ,在迷走神经刺激下 ,肺静脉刺激诱发房颤的房性早搏数 ,随着刺激电压从 0 .6到 3V的增加 ,从 7个减少到 2个 (P <0 .0 5 )。 7条狗局部去神经后 ,6条狗在同样肺静脉刺激诱发房颤的电压条件下不能诱发房颤 ,其中有 3条在电压大于 9V时诱发房颤。结论 :在临近右肺静脉和左房交接处脂肪垫刺激可以将肺静脉灶性放电转变成房颤。因此 ,临床上自发的迷走神经丛的张力增高是肺静脉灶性放电转变成房颤的基础。     

肺静脉隔离对迷走神经功能及心房颤动易感性的影响

目的研究肺静脉隔离(PVI)对犬的心房迷走神经功能及心房颤动(简称房颤)易感性的影响。方法9条成年杂种犬,全麻下行颈交感-迷走神经干剥离术。静脉应用美托洛尔阻断交感神经活性。分别于肺静脉消融前后在基础状态及迷走神经刺激时测量窦性周长(SCL)、右心耳(RAA)、左心耳(LAA)、冠状静脉窦近端(CSp)和冠状静脉窦远端(CSd)的不应期(ERP)及心房易感窗口(VW)。结果①PVI前迷走神经刺激能明显降低SCL(P<0.001),PVI后迷走神经刺激对SCL影响较小(P>0.05)。②PVI前,迷走神经刺激能明显缩短心房各部位ERP(P均<0.05)。PVI后,迷走神经刺激对心房ERP的影响较小(P均>0.05)。③PVI前后基础状态下测得的VW无变化。PVI后迷走神经介导的房颤诱发率明显下降(P均<0.05)。结论PVI能导致迷走神经介导的窦房结抑制、心房不应期缩短能力及房颤易感窗口增加能力明显下降。     

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。     

心脏自主神经系统在心房颤动发生和维持中的作用

心脏自主神经系统(ANS)包括外在ANS与内在ANS,均同时含有肾上腺素能与胆碱能神经纤维。刺激实验动物(犬)的颈部迷走交感干或位于心房表面的神经丛可使其心房有效不应期(ERP)缩短,ERP离散度增加,心房颤动(简称房颤)的诱发性增加;不论有无器质性心脏病,某些房颤患者在房颤发作前表现出ANS张力的显著变化。针对实验动物(犬)的去神经措施,可以不同程度地消除心脏ANS刺激所介导的心房ERP缩短及其离散度增加,并使房颤的诱发率降低;针对房颤患者直接或间接、单独或辅助的心房神经丛消融治疗,可使部分患者房颤治愈,或显著提高肺静脉电隔离或环肺静脉消融治疗房颤的成功率。上述现象则可能与位于肺静脉及心房、特别是左心房的心脏自主神经纤维通过多种机制参与了房颤的发生与维持有关。     

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.     

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.     

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。     

Partial vagal denervation increases vulnerability to vagally induced atrial fibrillation

INTRODUCTION: Cervical vagal stimulation shortens the atrial effective refractory period (ERP) primarily in the high right atrium (HRA) and facilitates induction of atrial fibrillation (AF) by single premature HRA extrastimuli. We hypothesized that vagal denervation of the HRA prevents both ERP shortening in the HRA and AF induction during vagal stimulation. METHODS AND RESULTS: Vagal denervation of the HRA was achieved using radiofrequency catheter ablation (RFA) of the fat pad at the right pulmonary vein-atrial junction (RPV fat pad). Programmed stimulation was performed at each of four atrial sites to measure ERP and inducibility of AF during vagal stimulation. RPV fat pad RFA increased only the HRA ERP during vagal stimulation (70 +/- 8.7 vs 117 +/-14.8, P < 0.05). RPV fat pad RFA increased measures of dispersion of refractoriness, the standard deviation of ERP (24 +/- 2.1 vs 33 +/- 2.0, P < 0.01), and the standard deviation of AF cycle length (11 +/- 0.8 vs 22 +/- 1.7, P < 0.001) during vagal stimulation. RPV fat pad RFA increased the incidence of AF (15/28 vs 24/28, P < 0.05) and the vulnerability (22 +/- 4.7 vs 39 +/- 5.6, P < 0.01) to AF induction during vagal stimulation, particularly from left atrial premature beats. After RPV fat pad RFA, premature beats induced AF by causing conduction block primarily in the HRA and macroreentrant activation around the block. CONCLUSION: Partial right atrial vagal denervation facilitated rather than prevented initiation of vagally mediated AF.     

Pulmonary vein encircling ablation alters the atrial electrophysiologic response to autonomic stimulation

Objective Pulmonary vein encircling ablation is often effective in the treatment of atrial fibrillation (AF). The success of the procedure does not depend upon creation of continuous lines of block. Thus mechanisms by which pulmonary vein encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary vein encircling alters atrial autonomic function and that these alterations account in part for prevention of AF recurrences following ablation. Methods Atrial effective refractory periods (ERP) and AF inducibility were quantified in ten dogs before and during central autonomic nerve stimulation. Pulmonary vein encircling ablation was then performed and electrophysiologic testing repeated. In two dogs subjected to sham procedures measurements were repeated without performance of ablation. Hearts were examined histologically. Results Autonomic nerve stimulation led to decreased atrial refractoriness and increased AF inducibility and duration. Each of these effects were attenuated following pulmonary vein encircling (e.g., mean ERP decreased before (−23.7 ± 1.8, p < 0.001) but not after ablation (−2.3 ± 1.9, p = 0.25); AF inducibility increased by 26% before vs. 5% after ablation). No attenuation was seen in the sham operated animals. Histologic analysis following pulmonary vein encircling demonstrated destruction of some but not all autonomic ganglia. Conclusion Autonomic stimulation shortens atrial refractory periods and potentiates AF. Pulmonary vein encircling ablation partially destroys atrial autonomic inputs, attenuates the refractory period shortening effect of autonomic stimulation and decreases AF inducibility. Destruction of autonomic ganglia may contribute to the anti-fibrillatory effects of pulmonary vein encircling and warrants further investigation. Potential conflict of interest: PSS is a consultant to and receives grant support from Biosense Webster Research Support. This study was supported by a research alliance with Medtronic Inc., Minneapolis, MN.     

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.