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)     

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。     

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。     

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     

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。     

Unequal Atrial Stretch in dogs Increases Dispersion of Refractoriness Conducive to developing Atrial Fibrillation

Atrial Stretch Precipitates Atrial Fibrillation. Introduction: We have shown previously that acute atrial dilation prolonged atrial refractoriness. We hypothesized that this increase in refractoriness might be heterogeneous and could create an electrophysiologic substrate leading to atrial fibrillation. The purpose of the present study was to test that hypothesis. Methods and Results: We studied 23 anesthetized open chest dogs. Bipolar plunge electrodes were placed in the medial free wall of the right atrium (thin region) and in the lower crista terminalis of the right atrium (thick region). Two bipolar plunge electrodes were also placed in the left ventricular apex to stimulate and record. Atrial effective refractory period (ERP) was measured in a group of nine dogs using the atrial extrastimulus method (A1A2) in two ways: during atrial pacing (AP) and during simultaneous atrioventricular (AV) pacing that achieved an AV interval of 0 msec (AV = 0). One liter/hour of normal saline was infused intravenously to elevate right atrial pressure and produce right atrial stretch. Atrial ERPs were measured before and after the normal saline infusion. To compare the extent of atrial stretch produced by volume overload, two pairs of sonomicrometer transducers were implanted in the thick and thin regions in a separate group of six dogs. The area encompassed by sonomicrometers was measured before and after saline infusion. The inducibility of atrial fibrillation was compared before and after saline infusion using rapid AP in another group of five dogs. Atrial pressure during sinus rhythm increased from 5.1 ± 0.96 mmHg to 6.3 ± 0.93 mmHg after normal saline infusion (P < 0.01). ERP increased in the thin free wall from 151 ± 14.3 to 172 ± 14.7 msec (AV = 0), and from 149 ± 12.0 to 170 ± 14.3 msec (AP). ERP increased in the thick crista terminalis from 134 ± 9.9 to 147 ± 10.2 msec (AV = 0), and from 133 ± 7.9 to 146 ± 9.8 msec (AP) (P < 0.01). The increase in ERP in the thin free wall exceeded that in the thick crista terminalis (P < 0.01), increasing the dispersion of atrial ERP. After 500-mL saline infusion for 30 minutes, the increase of area in the thin region was 12.8%± 3.7%, and that in the thick was 3.5%± 3.2%. The increase of the area in the thin region after 1000 mL for 1 hour was 18.8%± 6.2%. and that in the thick region was 6.3%± 5.1% (P < 0.01). Atrial fibrillation was not induced in any dog before saline infusion, hut induced in all five dogs after saline infusion. Conclusions: Atrial ERP in the thin right atrial free wall exceeds the ERP of the thick cristaterminalis, and an increase in atrial pressure produced by saline infusion exaggerates this ditterence by stretching thin segments of the atrial myocardium more than it stretches thick regions. Thus, atrial stretch, by increasing the dispersion of atrial ERP, may be conducive to the development of atrial fibrillation.     

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.     

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。     

Vagal stimulation prior to atrial rapid pacing protects the atrium from electrical remodeling in anesthetized dogs.

Atrial electrical remodeling is thought to be the cause of the maintenance of atrial fibrillation (AF). Although the initiation and maintenance of AF is partially associated with autonomic nervous tone, vagally mediated AF does not tend to become permanent. Therefore, the effects of preceding vagal stimulation (VS) on the atrial effective refractory period (ERP) under electrical remodeling conditions were investigated in anesthetized dogs. Atrial ERPs were measured at 5 sites before and after a 7-h period of atrial rapid pacing in the control group. In the VS group, the vagus nerve was stimulated for 20 min before a period of atrial rapid pacing. Atrial rapid pacing shortened the ERP at each site in the control group (electrical remodeling). On the other hand, atrial rapid pacing after VS did not shorten the ERP at any site in the VS group. Tetrodotoxin, which was administered into the fatty tissue overlying the right atrial side of the right pulmonary vein junctions, blocked the protective effect of VS against the shortening of the ERP induced by atrial rapid pacing. In contrast, atropine did not interfere with such protective effects. These results suggest that VS prior to atrial rapid pacing protects the atrium from atrial electrical remodeling.     

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.     

去自主神经条件下迷走神经刺激对肺静脉不同部位有效不应期的影响

目的探讨去自主神经条件下迷走神经刺激对肺静脉不同部位有效不应期(ERP)的影响。方法10只成年健康杂种犬,常规戊巴比妥钠麻醉,气管插管,接呼吸机,暴露并切断双侧颈迷走神经干,破坏颈交感神经节。双侧开胸,刺激电极分别与左、右心耳、左房及四支肺静脉缝合,行程序刺激,观察在基础状态、双侧强迷走刺激及阿托品作用时肺静脉不同部位ERP的变化。结果迷走神经刺激明显缩短肺静脉不同部位的ERP,而阿托品则可拮抗这种缩短。结论迷走神经刺激缩短肺静脉的ERP并参与房颤的发生。     

Ablation of Ligament of Marshall Attenuates Atrial Vulnerability to Fibrillation Induced by Inferior Left Atrial Fat Pad Stimulation in Dogs

Ligament of Marshall and Atrial Fibrillation Induction. Background: The role of ligament of Marshall (LOM) in the mechanism of “vagal” atrial fibrillation (AF) is still unknown. Objective: To investigate the impact of LOM ablation on atrial vulnerability to AF induced by inferior left atrial fat pad (ILAFP) stimulation in dogs. Methods: AF inducibility and atrial effective refractory period (ERP) were elevated before and after LOM ablation in 8 of 14 dogs (the ablation group). Same protocol but without LOM ablation was conducted in the remaining 6 dogs (the control group). The activation patterns of LOM and left pulmonary veins (LPVs) during sustained AF were analyzed. The distribution of epicardial cholinergic nerve fibers between LOM and ILAFP was investigated in the control group. Results: Ablation of LOM significantly attenuated AF inducibility (87.5% vs 33.3%, P < 0.001) and prolonged ERPs of the structures in contiguity with LOM (P < 0.05) in the ablation group. In contrast, there was no significant change in ERPs and AF inducibility in the control group. During sustained AF, fractionated atrial electrograms were more common in the LOM area than the LPVs (84% vs 18% of the analyzed episodes, P < 0.001). In 46.7% of the episodes with identifiable LOM spikes, atrial potentials, and LOM spikes were related in 2:1 or 3:2 pattern during the intermittent organized activity. Acetylcholinesterase staining revealed a close cholinergic nerved relationship between LOM and ILAFP. Conclusions: LOM plays a critical role in maintaining AF induced by stimulation of ILAFP. Ablation of LOM can markedly attenuate AF inducibility in this model. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1024‐1030, September 2010)     

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.     

Atrial natriuretic peptide has dose-dependent, autonomically mediated effects on atrial refractoriness and repolarization in anesthetized dogs

INTRODUCTION: Atrial natriuretic peptide (ANP) may alter electrophysiological properties of the heart and possibly have a role in arrhythmogenesis. However, previous studies have yielded conflicting results and have not fully considered whether ANP's cardiac electrophysiological effects are mediated via direct actions and/or indirectly via the autonomic nervous system. This study's aim was to establish whether ANP infused at pathophysiological and pharmacological doses has significant in vivo cardiac electrophysiological effects and to determine whether these effects are directly or autonomically mediated. METHODS AND RESULTS: Electrophysiologic and hemodynamic effects of ANP infusion (human ANP at 15-600 ng/kg per minute) were examined in chloralose-anesthetized dogs under conditions of varying autonomic blockade. In autonomically intact dogs (n = 12), low-dose ANP (15 ng/kg per minute) shortened atrial effective refractory period (ERP) (P < 0.001) and monophasic action potential duration (MAPD90) (P < 0.05) at 600, 500, and 400 msec atrial paced cycle lengths and reduced right atrial pressure (P < 0.05) but did not alter mean arterial pressure. After either combined vagal and beta-adrenergic blockade (vagotomy plus atropine plus propranolol, n = 7) or selective vagal blockade (n = 9), low-dose ANP no longer altered atrial ERP or MAPD90. Higher ANP doses (150 and 600 ng/kg per minute) decreased mean arterial and right atrial pressures (P < 0.001) but did not alter atrial ERP, MAPD90, or other electrophysiological parameters including atrial fibrillation threshold, ventricular ERP, and MAPD90. CONCLUSION: ANP has dose-dependent, autonomically mediated effects on atrial refractoriness and repolarization.     

房室结慢径消融对心房电生理性质的影响

目的 慢径消融降低了心房颤动(房颤)的易感性,但具体机制不明.本文旨在探讨消融后心房电生理性质的改变及其具体机制.方法 32例房室结折返性心动过速患者,测量射频消融前后窦性心率及高位右心房、低位右心房、冠状静脉窦近端和远端各部位的有效不应期和易感窗口,以及房室结快径前传不应期的变化.结果 (1)慢径消融前后下列部位的有效不应期的变化分别为:冠状静脉窦近端(21 8.1±21.8)ms,(235.3±23.6)ms,P＜0.0001;冠状静脉窦远端(230.9±21.0)ms,(244.7±25.1)ms,P＜0.01;低位右心房(198.8±26.7)ms,(219.7±28.7)ms,P＜0.005;高位右心房(214.4±35.1)ms,(213.4±37.3)ms,P=0.6.(2)在消融术后,房颤的诱发比例下降,冠状静脉窦近端的易感窗口显著降低(P=0.03),冠状静脉窦远端和低位右心房的易感窗口有所降低,高位右心房的易感窗口不变,但差异无统计学意义.(3)消融后窦性心率有一定程度的上升(72.1±5.6)次/min对(74±6.8)次/min,但差异无统计学意义(P=0.17).(4)慢径消融使快径前传不应期缩短,消融前后分别为(391±55)ms,(369±78)ms,P＜0.01.结论 慢径消融使心房多部位的电生理性质发生了改变,导致冠状静脉窦近端和远端,以及低位右心房的有效不应期延长,房颤诱发几率降低.该现象的原因可能与消融造成的迷走神经功能改变有关.     

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...     

快速右心房起搏对实验犬心房胶原纤维分布的影响

目的 实验探讨切除上腔静脉中部和主动脉根部脂肪垫(简称脂肪垫)对快速右心房(RA)起搏实验犬的心房胶原容积分数(CVF)的空间分布变化意义.方法 24只成年健康杂种犬雌雄不限,随机分为切除脂肪垫组、保留脂肪垫组和假手术组,每组8只.RA心外膜起搏6周,按左心房(LA)、RA、左心耳(LAA)、右心耳(RAA)、房间隔(AS)5个部位取材,Masson染色测算CVF,荧光定量聚合酶链反应技术检测缝隙连接蛋白(Cx)40和Cx43mRNA表达.结果 (1)假手术组和切除脂肪垫组CVF在部位分布上差异无统计学意义;保留脂肪垫组胶原增生明显,见于LAA和AS,P＜0.01.(2)假手术组Cx40mRNA含量分布在LA、RA、RAA、AS间差异无统计学意义;Cx40mRNA表达在切除脂肪垫组与保留脂肪垫组以LA、LAA增多且组间差异有统计学意义(P＜0.01).(3)假手术组Cx43mRNA含量优势表达于RA、RAA,P＜0.01;而在切除脂肪垫组LA、RA、RAA、AS其含量增多,在保留脂肪垫组的相应部位,其含量减少,P＜0.01.结论 快速RA起搏所致心房间质纤维增生具有空间各异向性,去迷走神经能抑制此效应.迷走神经效应影响起搏后Cx40mRNA与Cx43mRNA在心房与心耳间含量的表达.     

Daily oral verapamil before but not after rapid atrial excitation prevents electrical remodeling

BACKGROUND: Intravenous verapamil has been reported to prevent electrical remodeling induced by rapid atrial excitation of several minutes to several hours. However, the clinical efficacy of verapamil when taken orally and daily remains controversial. PURPOSE: We attempted to demonstrate our hypothesis that if verapamil prevents calcium (Ca) overload, its efficacy would be greater when taken before, rather than after, the onset of rapid atrial excitation. METHODS: In 24 dogs, pacing and recording electrodes were sutured onto the right atrium. After a 5-day recovery period, rapid atrial pacing at 400 ppm was started, followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After group; A). In another eight dogs, oral verapamil administration was begun 1 week before the initiation of rapid pacing (Before group; B). In the remaining eight dogs, only rapid atrial pacing was started, without oral verapamil (Control group; C). We measured the effective refractory period (ERP) and conduction velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing. RESULTS: In response to rapid atrial pacing, ERP, CV, WL decreased and progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these parameters did not change significantly and remained greater than those in A and C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05). The inducibility of AF tended to be lower, and the fibrillation cycle length was longer in B than in A and C. CONCLUSIONS: Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia.     

Experimental study of the effect of the vagus nerve on atrial electrical remodeling

Recent studies have shown that rapid atrial activation causes atrial electrical remodeling (AER), which recovers quickly following withdrawal of stimulation. The underlying mechanisms, however, are incompletely understood. The purpose of the present study, therefore, was to characterize the effect of the vagus on AER as well as define possible mechanisms of the phenomenon. Eight dogs were used in the study for 3 consecutive protocols. In the first, the dogs were subjected to atrial pacing at 800 ppm for 7 hours. Every hour, pacing was interrupted for a short time and atrial effective refractory period (AERP) was measured at 6 sites. The rapid atrial pacing was then discontinued and the electrophysiological study was repeated every hour for another 7 hours. Time-domain parameters of heart rate variability (HRV) were also computed 1 hour before pacing as well as each of 7 hours after the rapid atrial pacing protocol. The second program was performed two weeks after the first; 0.04 mg/kg of atropine was administered intravenously 30 min before pacing, and then 0.007 mg/kg was added at each hour. Parameters of HRV were not evaluated. Finally, the 8 dogs were subjected to the third protocol 2 weeks after completion of the second; 0.2 mg/kg of propranolol was given intravenously 30 min before pacing, and 0.04 mg/kg was added at each hour. The dispersion of AERP (dAERP) was calculated as, maximum AERP minus minimum AERP. There was a prompt decrease in AERP as the result of pacing (P<.05), but dAERP did not change significantly. The AERP recovered quickly, and dAERP increased from 21 +/-5.3 ms to 40 +/- 7.4 ms (P<.05) after cessation of pacing. At the same time, the parameters of HRV increased (P<.05) after cessation of pacing. The AERP increased from 128 +/- 12 ms to 135 +/- 12 ms and from 127 +/- 12 ms to 142 +/- 14 ms (P<.05) after vagal and autonomic blockade. However, AERP decreased during pacing (P<.05) with vagal or autonomic blockade, but dAERP did not change significantly during or after pacing. These results suggest that vagal and autonomic blockade can not prevent AER, but a high vagal tone is associated with a high dAERP during recovery from AER, indicating that the vagus and sympathetic have a synergistic effect on the refractory period.     

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.