Autonomic mechanism for chronic atrial electrical remodeling induced by rapid atrial pacing in ambulatory danines

Objetives The mechanism for changes in the electrophysiological properties of the atria during rapid pacing induced atrial fibrillation(AF) is not well understood.We aimed to investigate the contribution of intrinsic cardiac autonomic nervous system(ICANS) in chronic atrial electrical remodeling and AF induced by rapid atrial pacing for 4 weeks. Methods Twelve adult mongrel dogs weighing 15 to 20 kg were assigned to two groups;group 1(experimental group,n= 7) and group 2(control group,n =5).All dogs were anesthetized with propofol and mechanically ventilated via endotracheal tubes.The chest was entered via bilateral mini-thoracotomy at the fourth intercostals space.Bipolar pacing electrode was sutured to the right atrial appendage.Four-electrode catheters(Biosense-Webster,Diamond Bar,CA) were secured to allow recording at the right and left atriaum.All tracings from the electrode catheters were amplified and digitally recorded using a computer-based Bard Laboratory System (CR Bard Inc,Billerica,MA).Electrograms were filtered at 50 to 500 Hz.Continuous rapid pacing(600 bpm, 2×threshold[TH]) was performed at the right atrial appendage. Ganglionated Plexi(GP) was localized by applying high frequency stimulation(HFS;20 Hz,0.1ms duration, 0.5 to 4.5 V)with a bipolar stimulation-ablation probe electrode (AtriCure,West Chester,OH).Group1 underwent ablation of bilateral GP and ligament of Marshall followed by 4-week pacing.Group 2 underwent sham operaton without ablation of GP and ligament of Marshall followed by 4-week pacing.The effective refractory period(ERP) and window of vulnerability(WOV) were measured at 2×TH before(baseline) and every week after GP ablation.WOV was defined as the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF.GP consist of the anterior right ganglionated plexi(ARGP) located in the fat pad at the right superior pulmonary vein(RSPV)-atrial junction;the inferior right ganglionated plexi(IRGP) located at the inferior vena cava/right atr     

缬沙坦对心房快速起搏犬心房电、结构和功能重构的影响

心房颤动（AF）使心房发生电、结构和功能重构，促进AF发作并持续。新近研究提示，AF时心房重构与心房肌肾素-血管紧张素系统（RAS）激活关系密切。本研究观察缬沙坦对AF犬心房重构的防治作用。     

伊贝沙坦对快速心房起搏家兔心房电重构的影响

目的观察伊贝沙坦对心房快速起搏8h家兔心房电重构及心房肌细胞超微结构改变的影响。方法将12只家兔随机分为伊贝沙坦组和对照组。经颈内静脉将电极置入右心房,以600次/min行快速心房起搏,分别测定起搏前及起搏后0.5h、1h、4h、8h及停止起搏后10min、20min、30min,S1S1为200ms、150ms时的心房有效不应期(AERP200、AERP150);取未起搏家兔及每组起搏8h后家兔右心耳组织观察超微结构。结果①心房快速起搏8h,对照组家兔AERP缩短,起搏0.5h内AERP缩短幅度最明显;AERP频率自适应性出现了下降—逆转;停止起搏后30minAERP及AERP频率自适应性基本恢复至起搏前水平(最初10min恢复迅速)。②伊贝沙坦组家兔8h心房快速起搏过程中各时间点AERP较起搏前无明显变化。③8h心房快速起搏后对照组家兔心房肌细胞超微结构可见线粒体肿胀、脊溶解、糖原聚集,伊贝沙坦组家兔心房肌细胞超微结构基本正常。结论伊贝沙坦可阻止8h心房快速起搏所致的心房电重构和心房肌细胞超微结构改变。     

Short-term rapid atrial pacing produces electrical remodeling of sinus node function in humans

INTRODUCTION: Depression of sinus node function occurs in dogs and in patients after cessation of atrial flutter and fibrillation. We tested whether transient atrial pacing might produce similar changes in humans. METHODS AND RESULTS: We studied the impact of short-term rapid atrial pacing, simulating atrial tachyarrhythmias, on sinoatrial conduction time (SACT) and corrected sinus node recovery time (CS-NRT) in 10 patients undergoing electrophysiologic study. None had recognizable structural heart disease, history of atrial fibrillation or flutter, autonomic dysfunction, or any tachycardia for at least 24 hours before study. All cardiac drugs were discontinued >5 half-lives prior to study. No patient had significant hypotension during atrial stimulation. SACT and CSNRT were measured at baseline, and sinus node reset zone was determined. Right atrial pacing was performed for 10 to 15 minutes, after which SACT and CSNRT were measured again. Both parameters increased significantly, from 423+/-208 msec to 491+/-214 msec and from 80+/-50 msec to 96+/-53 msec, respectively (P = 0.02 and P < 0.001, respectively). CONCLUSION: Rapid atrial pacing for only 10 to 15 minutes, simulating transient atrial tachyarrhythmias, alters sinus node function in humans. Additional studies are needed to evaluate the mechanism, but the clinical implication is that even transient episodes of atrial tachyarrhythmias can cause sinus node remodeling in patients.     

Modulation of vagal activity to atria electrical remodeling resulted from rapid atrial pacing

Background Atrial electrical remodeling(AER) plays an important role in the pathogenesis and maintenance of atrial fibrillation.However,little is known about modulation of vagal activity to AER.This study aimed to investigate the relationship between vagal moduation and AER.Methods Twenty four adult mongrel dogs under general anesthesia were randomized into 3 groups.Sympathetic activity was blocked by administration of metoprolol in 3 groups.The changes in vagal modulation to atria after AER were observed in 10 dogs without vagal interruption in group A.The effects ofvagal intervention on AER were investigated in 8 dogs with administration of atropine in group B.The impact of aggressively vagal activity on AER was studied in 6 dogs with bilateral cervical vag sympathetic trunks stimulation during AER in group C.Bilateral cervical vagosympathetic trunks were decentralized. Multipolar catheters were placed into high right atria (RA),coronary sinus (CS) and right ventricle (RV).AER was induced by 600 bpm pacing through RA catheter for 30 minutes.Atrial effective refractory period (ERP) and vulnerability window (VW) of atrial fibrillation were measured with and without vagal stimulation before and after AER.Results In group A,ERP decreased significantly at baseline and during vagal stimulation after AER compared with that before AER (all P<0.05).In group B,ERP remained unchanged at baseline and vagal stimulation after AER compared with that before AER (all P>0.05).In group C,ERP shortened significantly at baseline and vagal stimulation after AER compared with that before AER (all P<0.05).ERP shortening after AER in Groups A and C increased significantly than that in group B (all P<0.05).Atrial fibrillation could not be induced at baseline (VW close to 0) before and after AER in three groups.VW became widen significantly during vagal stimulation after AER compared with that before AER in Groups A and C (all P<0.05),while VW remained unchanged in group B (VW close to 0).Conclusions Short-term AER result     

Electrical remodeling of the canine superior vena cava after chronic rapid atrial pacing

Background The superior vena cava (SVC) might serve as the trigger and/or substrate for paroxysmal atrial fibrillation (AF). However, the electrophysiological properties of the SVC with chronic AF are unknown. The purposes of this study were to investigate the electrophysiological properties of the SVC and the electropharmacological effects of intravenous dl–sotalol on the canine SVC after chronic rapid atrial pacing (RAP). Methods and results In the control group, the effective refractory period (ERP), conduction velocity, and AF inducibility of the SVC were assessed in 6 normal dogs before and after an infusion of dl–sotalol. In the experimental group, the ERP, conduction velocity, and AF inducibility of the SVC were assessed before and after dl–sotalol administration in 10 dogs after 8 weeks of RAP. The SVC showed a shorter ERP, decreased slope of rate–adaptation of the ERP, increased ERP dispersion, a decreased conduction velocity, and increased inducibility and duration of AF initiated from the SVC in the RAP dogs. In the RAP dogs, intravenous dl–sotalol significantly increased the ERP, but dlsotalol did not change the slope of rate–adaptation of the ERP, dispersion of the ERP, conduction velocity, inducibility, or duration of AF initiated from the SVC. Conclusions The present study demonstrates that the canine SVC shows significant electrical remodeling and increased AF vulnerability after chronic RAP. Intravenous dl–sotalol was unable to decrease the inducibility or duration of AF initiated from the SVC.Supported in part by grants from the National Science Council (NSC 93-2314- B-341-001) and Shin Kong Wu Ho-Su Memorial Hospital (SKH-TMU-92-28, SKHTMU- NSC-93-01), Taipei, Taiwan, R.O.C.     

氯沙坦对家兔快速心房起搏心房电重构及L-型钙通道的影响

目的:通过人工心脏起搏的方法制备家兔急性心房颤动(Af)动物模型,探讨Af时心房发生电重构的机制,并观察氯沙坦对电重构的影响.方法:30只家兔,随机分为3组(每组10只):对照组、0.9%氯化钠起搏组、氯沙坦起搏组;以600次/min的频率起搏心房8 h,并分别于起搏后2、4、6、8 h测定心房有效不应期(AERP)变化及L-型钙通道的电流密度.结果:①经快速起搏8 h,0.9%氯化钠起搏组较对照组各个基础周长下的AERP均显著下降.氯沙坦起搏组较对照组AERP无明显变化.②0.9%氯化钠起搏组较对照组心房肌ICa-L降低;氯沙坦起搏组较对照组心房肌ICa-L未见显著降低;氯沙坦起搏组较0.9%氯化钠起搏组心房肌ICa-L差异无统计学意义,但ICa-L的标准差显著降低.结论:①快速心房起搏可引起AERP缩短及AERP频率适应性不良为特征的心房肌电重构,氯沙坦可以预防电重构的发生.②快速心房起搏可以导致心房肌ICa-L的降低和离散度的增高;氯沙坦可以抑制ICa-L离散度的增加从而降低Af的潜在危险.     

培哚普利联合醛固醇受体拮抗剂对心房纤颤犬心房结构重构的影响

目的:观察培哚普利和螺内酯及二者联用对长期心房快速起搏诱发心房纤颤(房颤,AF)犬心房结构和功能重构的影响。方法:实验犬24只,随机分为4组,即对照组、培哚普利组(P组)、螺内酯组(S组)和二者联用组(P+S组)。各组心房快速起搏8周,建立AF犬模型。分别于起搏前、起搏4周及8周测定血浆血管紧张素II(AngII)和醛固酮(Ald)水平;起搏前及起搏后8周,测定左心房结构和功能变化;起搏8周后停止起搏,观察各组犬AF维持的例数及AF自行持续时间;Masson染色检测各组犬心房肌胶原容积分数(CVF)改变。结果:与对照组相比,P组、S组和P+S组犬起搏4周和8周后血浆AngII及Ald水平明显降低,起搏8周后左心房左右径、上下径、收缩末期容积和舒张末期容积明显减小,左心房射血分数显著增大,停止起搏后AF维持率明显减少,AF平均持续时间明显缩短,CVF值明显降低。而3个用药组相比差异无统计学意义。结论:培哚普利和醛固酮受体拮抗剂(螺内酯)能够阻止长期心房快速起搏AF犬心房结构功能的改变及心房纤维化,减少AF发生率及持续时间,但二者联用效果并不优于单药。     

基质金属蛋白酶在心房颤动犬心房结构重构中的作用

目的 探讨基质金属蛋白酶-9（MMP-9）和组织型基质金属蛋白酶抑制因子-1（TIMP-1）在快速起搏心房颤动（房颤）动物模型心房结构重构中的作用和Ca^2＋超载对MMP-9激活的影响。方法 14只犬随机分为房颤组（n=8）和对照组（n=6），右心房快速起搏（350～450次／min）8周建立房颤动物模型。取左心房组织，采用半定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学法检测MMP-9和TIMP-1 mRNA和蛋白质表达，采用Masson染色测定心房肌组织胶原含量，采用超声心动图测量左心房内径，同时还测定心房肌组织Ca^2＋浓度。结果 与对照组比较，房颤组心房肌胶原含量、Ca^2＋浓度和左心房内径增加（P〈0．05）；房颤组左心房心肌组织MMP-9 mRNA表达升高45％（P〈0．01），蛋白质水平表达增加19．5％（P〈0．001）；TIMP-1 mRNA表达增加46．67％（P〈0．01），TIMP-1蛋白质水平表达下调8．33％（P〈0．01）；MMP-9 mRNA表达与左心房内径、Ca^2＋浓度和心肌胶原含量正相关（P〈0．05）；TIMP-1 mRNA表达与左心房内径、心肌胶原含量和MMP-9 mRNA表达正相关（P〈0．05）。结论 MMP-9／TIMP-1平衡失调可能是慢性房颤心房肌细胞外基质重构和心房扩大的重要分子机制，细胞内Ca^2＋超载可能是MMPs的重要激活途径。     

Effects of verapamil and procainamide on acute atrial electrical remodeling induced by short-term rapid atrial pacing in humans

Atrial electrical remodeling (ER) after spontaneous or pacing-induced atrial fibrillation has been previously described in humans. We investigated atrial ER induced by a 5-minute period of rapid atrial pacing and the pharmacologic effects of verapamil and procainamide on this atrial ER phenomenon. The atrial effective refractory periods (ERPs) at drive cycle lengths of 400 (ERP 400 ) and 600 (ERP 600 ) ms, at five representative atrial sites (high right atrium [HRA]; proximal, middle and distal coronary sinus; interatrial septum), were determined in 20 patients at baseline and immediately after cessation of a 5-minute period of rapid pacing from the HRA at a rate of 150 bpm. The degrees of atrial ERP 400 and ERP 600 shortening after pacing were calculated as acute atrial ER. The same protocol was repeated in another 15 patients after intravenous administration of verapamil (0.15 mg/kg) and in another 15 patients after intravenous administration of procainamide (15 mg/kg). The results demonstrated that, in the control state acute atrial ER can be significantly demonstrated at each atrial representative site ( p < 0.001). The mean ERP 400 and ERP 600 shortenings were 9 +/- 4% and 8 +/- 4%, respectively. After procainamide infusion, but not after verapamil, baseline ERP 400 and ERP 600 values were significantly prolonged at the five representative atrial sites ( p < 0.01). Acute atrial ER could still be demonstrated at each atrial site after procainamide or verapamil infusion ( p < 0.001). In conclusion, acute atrial ER can be demonstrated after only a 5-minute period of rapid atrial pacing in humans. Intravenous verapamil or procainamide does not abolish this ER process.     

Inducibility of atrial fibrillation during electrophysiologic evaluation is associated with increased dispersion of atrial refractoriness

The impact of atrial dispersion of refractoriness (Disp_A) in the inducibility and maintenance of atrial fibrillation (AF) has not been fully resolved. AIM: To study the Disp_A and the vulnerability (A_Vuln) for the induction of self-limited (<60 s) and sustained episodes of AF. METHODS AND RESULTS: Forty-seven patients with paroxysmal AF (PAF): 29 patients without structural heart disease and 18 with hypertensive heart disease. Atrial effective refractory period (ERP) was assessed at five sites--right atrial appendage and low lateral right atrium, high interatrial septum, proximal and distal coronary sinus. We compared three groups: group A - AF not inducible (n=13); group B - AF inducible, self-limited (n=18); group C - AF inducible, sustained (n=16). Age, lone AF, hypertension, left atrial and left ventricular (LV) dimensions, LV systolic function, duration of AF history, atrial flutter/tachycardia, previous antiarrhythmics, and Disp_A were analysed with logistic regression to determine association with A_Vuln for AF inducibility. The ERP at different sites showed no differences among the groups. Group A had a lower Disp_A compared to group B (47+/-20 ms vs 82+/-65 ms; p=0.002), and when compared to group C (47+/-20 ms vs 80+/-55 ms; p=0.008). There was no significant difference in Disp_A between groups B and C. By means of multivariate regression analysis, the only predictor of A_Vuln was Disp_A (p=0.04). Conclusion: In patients with PAF, increased Disp_A represents an electrophysiological marker of A_Vuln. Inducibility of both self-limited and sustained episodes of AF is associated with similar values of Disp_A. These findings suggest that the maintenance of AF is influenced by additional factors.     

Electrical remodeling in fibrillating canine atrium: action potential alternans during rapid atrial pacing and late phase 3 early afterdepolarization after cessation of rapid atrial pacing

Sustained atrial fibrillation (AF) was induced by atrial burst pacing, and monophasic action potentials (MAPs) were recorded. MAP alternans was observed at a cycle length (CL) of 167.5 ± 28.2 msec before burst pacing and 201.3 ± 40.2 msec after burst pacing. AF > 5 minutes duration was induced in 1 dog in the control condition but in all 8 dogs after burst pacing. The difference in RA MAPD(80) of the first spontaneous beat and steady-state sinus rhythm was significantly larger after atrial burst pacing than before atrial burst pacing (31.5 ± 15.9 msec versus 8.2 ± 9.0 msec) In 4 dogs, late phase 3 early after depolarization was observed after rapid atrial pacing. Rapid atrial pacing-induced electrical remodeling includes APD alternans during rapid atrial pacing and also causes an increase in the MAPD of the initial several beats and the development of late phase 3 early afterdepolarizations after a sudden increase in CL.     

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.     

快速心房起搏引起猪心房颤动时心房结构的变化及替米沙坦的预防作用

目的建立猪实验性心房颤动(atrial fibrillation,AF)模型,观察心房结构重构的变化和替米沙坦(TMST)干预的作用,测定血管紧张素转化酶2(ACE2)和胶原蛋白-Ⅰ的变化。方法将18头猪按随机数字表分为对照组(NC组)、快速心房起搏组(RAP组)、RAP+TMST组。闭胸法建立猪的持续性AF模型,超声测量实验前、后心室收缩末期左、右心房面积(LAESA、RAESA)变化;应用程序刺激检测AF的诱发率和持续时间;通过伊红(HE)染色、Masson染色和蛋白印迹法(Western blot)检测ACE2和胶原蛋白-Ⅰ的变化。结果与RAP组相比,RAP+TMST组LAESA、RAESA扩大减轻,AF诱发率降低、持续时间缩短,胶原蛋白-Ⅰ减少,而ACE2表达明显增加。RAESA与胶原蛋白-Ⅰ呈正相关关系(r1=0.956,P<0.01),RAESE与ACE2、ACE2与胶原蛋白-Ⅰ均呈负相关关系(r2=-0.966,r3=-0.948,P<0.01)。结论猪AF模型心房肌出现结构重构的病理表现,ACE2表达失衡与AF结构重构密切相关;TMST可降低AF的发生率及持续时间,明显改善心房结构重构。     

自主神经系统阻断对经肺静脉短阵快速起搏犬心房急性电重构的影响

目的探讨阻断自主神经系统对经肺静脉快速起搏造成的急性电重构的影响。方法成年杂种犬22只,随机分为对照组、阿托品组、美托洛尔组和阿+美组。首先测量起搏周长（PCL）分别为350 m s、400 m s时心房有效不应期（AERP）,以能够1∶1起搏肺静脉的最快频率刺激肺静脉10 m in,在刺激中止后即刻、5、10、15、20 m in时重复测量AERP。比较各组在起搏前后AERP和AERP频率适应性的变化。结果短阵快速肺静脉刺激可引起AERP明显缩短,AERP频率适应性下降,阻断迷走神经后明显减小电重构的程度。结论阻断迷走神经能明显减小短阵快速肺静脉刺激造成的心房电重构的程度     

Increased dispersion and shortened refractoriness caused by verapamil in chronic atrial fibrillation

OBJECTIVES: The objective was to assess the effect ofverapamil on atrial fibrillation (AF) cycle length and spatial dispersion of refractoriness in patients with chronic AF. BACKGROUND: Previous studies have suggested that verapamil prevents acute remodeling by AF. The effects of verapamil in chronic AF are unknown. METHODS: During electrophysiologic study in 15 patients with chronic AF (duration >1 year), 12 unipolar electrograms were recorded from right atrial free wall, right atrial appendage and coronary sinus, along with monophasic action potential recordings from the right atrial appendage. The mean fibrillatory interval at each atrial recording site was used as an index for local refractoriness. Dispersion of refractoriness was calculated as the standard deviation of all local mean fibrillatory intervals expressed as a percentage of the overall mean fibrillatory interval. After baseline measurements, verapamil (0.075 mg/kg intravenous in 10 min) was infused and the measurements were repeated. RESULTS: After administration ofverapamil, mean fibrillatory intervals shortened by a mean of 16.6 +/- 3.3 ms (p < 0.001) at the right free wall, 15.0 +/- 3.5 ms (p < 0.001) at the appendage and 17.1 +/- 3.2 ms (p < 0.01) in the coronary sinus. Monophasic action potential duration decreased by 15.9 +/- 4.0 ms (p < 0.01). Dispersion of refractoriness increased in all patients from 3.8 +/- 0.8 to 5.1 +/- 1.8 (p < 0.001). A strong correlation between mean fibrillatory intervals and action potential duration was found, both before and after verapamil. CONCLUSIONS: Verapamil caused shortening of refractoriness and increase in spatial dispersion of refractoriness in patients with chronic AF. This implies that verapamil is not useful in reversing the remodeling process in these patients.     

快速心房刺激对P波时限及离散度的影响

目的分析快速心房刺激对P波时限及离散度的影响.方法在74例射频消融术及82例经食管心房调搏检查中,用180ppm的S1S1刺激心房3min,在刺激前后立刻记录12导联同步心电图,通过心电图测出刺激前后的最大P波时限、最小P波时限及P波离散度,然后进行比较.结果射频消融组最大P波时限在心房刺激后比刺激前有显著性延长（p=0.002）,最小P波时限及P波离散度无显著性差异,食管心房调搏组最大P波时限及P波离散度在心房刺激后比刺激前有显著性增加（p=0.001）,最小P波时限无显著性差异.结论快速心房刺激能引起心房传导时间延长,非均质电活动的离散程度增加.最大P波时限及P波离散度是可以用来评价心房电重构的简便而无创的指标.     

兔右房快速起搏后交感神经重构的动态变化

目的:动态观察快速起搏右房后心房肌神经生长因子(NGF)和酪氨酸羟化酶(TH)的动态表达,从分子水平揭示心房颤动(房颤)交感神经动态重构的规律。方法:从快速起搏后的兔右心房和左心房取材,通过免疫组化并结合计算机图像处理技术对心肌中NGF蛋白表达及交感神经支配进行研究。结果:与假手术组比较,快速起搏后4h,NGF蛋白的表达在右心房[(412.75±7.49)μm2/mm2∶(563.87±15.53)μm2/mm2]和左心房[(275.87±16.74)μm2/mm2∶(449.75±17.58)μm2/mm2]心肌中明显增加(P0.05);TH阳性神经纤维平均密度[右心房(72.00±8.02)μm2/mm2∶(83.87±7.18)μm2/mm2,左心房(58.00±10.65)μm2/mm2∶(70.50±6.65)μm2/mm2,P0.05]均显著增加;且右心房和左心房中交感神经支配与NGF蛋白的表达呈正相关(r=0.53,P0.05)。快速起搏后12h,兔心房中NGF蛋白的表达[右心房(869.50±17.28)μm2/mm2,左心房(830.75±11.73)μm2/mm2]与TH阳性神经纤维平均密度[右心房(120.87±8.57)μm2/mm2,左心房(100.25±10.25)μm2/mm2]均明显高于假手术组及快速起搏后4h组(P0.05~0.01),且二者呈正相关(r=0.69,P0.05)。快速起搏后24h,NGF蛋白表达[右心房(1115.7±92.35)μm2/mm2,左心房(949.12±43.20)μm2/mm2]及TH阳性神经纤维平均密度[右心房(158.12±11.28)μm2/mm2,左心房(121.12±14.71)μm2/mm2]均明显高于快速起搏后4h、12h(P0.01~0.001)。结论:快速起搏后心肌中神经生长因子蛋白呈动态表达,并与交感神经支配相关,提示神经生长因子可能在心肌局部发挥神经营养作用,进而参与交感神经的重构。