Regional differences in the recovery course of tachycardia-induced changes of atrial electrophysiological properties

BACKGROUND: Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied. METHODS AND RESULTS: In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann's bundle. CONCLUSIONS: The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.     

Long-term changes in sequence of atrial activation and refractory periods: no evidence for "atrial memory".

OBJECTIVES: The purpose of this study was to test whether the spatial distribution of the atrial refractory period (AERP) and the vulnerability to atrial fibrillation (AF) are altered by long-term changes in the sequence of atrial activation. BACKGROUND: The spatial distribution of the AERP plays an important role in AF. Changes in the activation sequence have been postulated to modulate atrial repolarization ("atrial memory"). METHODS: Six goats were chronically instrumented with epicardial atrial electrodes to determine activation time and AERP at 11 different areas of the right (RA) and left (LA) atrium and the Bachmann bundle. Activation time and AERP were measured during sinus rhythm and during prolonged RA and LA pacing (1 week RA pacing, 2 weeks LA pacing, 1 week RA pacing; 150 bpm). Inducibility of AF was determined by the number of atrial sites where single premature stimuli induced AF paroxysms >1 second. RESULTS: During sinus rhythm (106 +/- 4 bpm), AERP was longest at the Bachmann bundle and shortest at the LA free wall (185 +/- 6 ms and 141 +/- 5 ms, P < .001). In five of six goats, an inverse correlation between local activation time and AERP was found during sinus rhythm (r = -0.53 +/- 0.05; P < .05). The increase in atrial rate during RA and LA pacing caused an overall shortening of AERP from 167 +/- 6 ms to 140 +/- 6 ms (P < .001). However, a switch between long-term RA and LA pacing did not significantly change AERP at any of the 11 atrial regions and had no significant effect on AF inducibility. CONCLUSIONS: During sinus rhythm, an inverse relationship exists between the sequence of atrial activation and the local refractory period. However, long-term changes in the sequence of atrial activation do not alter the spatial distribution of AERP or the inducibility of AF.     

Inhomogeneity in the appearance of electrical remodeling during chronic rapid atrial pacing: evaluation of the dispersion of atrial effective refractoriness

In the present study, the long-term process of progression of electrical remodeling at various atrial sites, which is not well understood, was compared while monitoring continuously the electrophysiologic parameters at multirecording sites in canine atria during continuous atrial burst pacing. A rapid pacing device was implanted in 5 dogs, and continuous atrial burst pacing (400 beats/min) was delivered at the right atrial appendage (RAA). Four pairs of epicardial wire electrodes were sutured on (1) the RAA, (2) Bachmann's bundle (BB), (3) the right atrium close to the inferior vena cava (IVC), and (4) the left atrium (LA). The distal ends of those wires were exteriorized posteriorly and used for pacing and recording. The atrial effective refractory period (AERP), AERP dispersion (AERPd), atrial conduction time (CT) and inducibility of atrial fibrillation (AF) were evaluated during burst pacing for 14 days and during the subsequent 7 days' recovery. The AERP at the LA pacing site was shorter than that at the other sites on day 0. The AERP shortening was greater in the RAA and LA sites than in the BB and IVC sites. The AERPd increased during pacing and reached the maximum level on day 3, and then decreased during the recovery phase. Prolongation of CT tended to be longer between the RAAand IVC sites than that between the other sites. The incidence of AF induction became higher in accordance with the time course of the rapid pacing phase. There was another peak of AF induction on days 7-10. In a canine chronic rapid atrial stimulation model, the progression of electrical remodeling (ie, the shortening of the AERP and the prolongation of the CT) was not homogeneous in both atria, the AERPd showed a temporal increase between days 3 and 7 and matched the increase in AF inducibility at the LA pacing site, the increase in the AERPd was mainly caused by more rapid AERP shortening at the RAA or LA sites, and the LA site always showed a shorter AERP than the other atrial sites in the control state and during the rapid pacing phase, whereas AF inducibility was higher at the LA site than the other sites.     

Effect of pilsicainide on atrial electrophysiologic properties in the canine rapid atrial stimulation model.

The heterogeneous process of atrial electrical remodeling (AER) in the canine rapid atrial stimulation model has been previously reported although it has been reported that a sodium channel blocker might suppress the shortening of the atrial effective refractory period (AERP), its effect on long-term electrical remodeling is unknown. In the present study, the effect of pilsicainide on AER was evaluated. The right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. In the RAA, Bachmann's bundle (BB), the right atrium near the inferior vena cava (IVC) and in the left atrium (LA), AERP, AERP dispersion (AERPd) and the inducibility of atrial fibrillation (AF) were evaluated at several time points of the pacing phase and the recovery phase (1 week). The same protocol was performed during the administration of pilsicainide (4.5 mg/kg per day) and the parameters were compared with the controls. In the control dogs, the AERP was significantly shortened by rapid pacing at all atrial sites studied and the AERP shortening (DeltaAERP) was larger at the RAA and LA sites (p<0.03). However, pilsicainide decreased these DeltaAERPs at all 4 atrial sites. AERPd was increased during the pacing phase whereas it was decreased during the recovery phase in the control dogs. In contrast, this pacing-induced AERPd was attenuated by the administration of pilsicainide. The AF inducibility was highest at the LA site in both groups, and the inducibility was lower in the pilsicainide group than the control group at all atrial sites. During the rapid pacing phase, the ventricular heart rate was significantly lower in the pilsicainide group than the control because of intra-atrial conduction block. In a canine rapid right atrial stimulation model, pilsicainide suppressed the shortening of the AERP at all atrial sites, possibly through the improvement of the hemodynamics as well as the action of the Na - Ca exchanger.     

钙对心房肌电重构影响的实验研究

目的 用动物试验模拟快速房律,观察心房电重构的电生理变化并对其机制进行初的探讨。方法 用8只羊自身随机对照,观察不同状态下和用不同药物时心房有效不应期（AERP）的变化,和心房颤动（房颤）的诱发率。结果（1）800次／min的快速心房刺激很快引起AERP的缩短,停止刺激后AERP的恢复也很快。单用维拉帕米可防止快速刺激引起AERP的缩短,而升高血血清钙显延缓停止刺激后的AERP的恢复,而且升高血清钙可消除维拉帕米对AERP的保护作用。（2）快速心房刺激后明显增加心房反复激动和房颤的诱导率。结论 （1）7h,800次／min的快速刺激可赞成心房电重构,电重构出现较早（30min内）,停止刺激后电重构很快恢复（1h)内,（2）心房电重构后容易诱发心房反复激动和房颤;（3）维拉帕米可预防心房电重构,升高血钙可延缓电重构的恢复。     

Bepridil inhibits sub-acute phase of atrial electrical remodeling in canine rapid atrial stimulation model.

Background The effect of bepridil, a multichannel blocker, on atrial electrical remodeling was evaluated in a canine rapid atrial stimulation model. Methods and Results In 10 beagle dogs, the right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. The atrial electrophysiological parameters, including effective refractory period (AERP), were evaluated at three atrial sites: RAA, the right atrium close to the inferior vena cava (IVC) and the left atrium (LA), during the time course of rapid pacing. Five of the dogs were given bepridil (10 mg . kg (-1) . day(-1) po). In the control group, AERP was significantly shortened at all atrial sites and the AERP shortening (DeltaAERP) was larger for the RAA and LA than at the IVC site (p<0.05). In the bepridil group, DeltaAERP was smaller than that of the controls at all atrial sites, and the AERP started to return slowly to the pre-pacing level in the second week, regardless of the continuation of rapid pacing. Conclusions In a canine rapid atrial stimulation model, bepridil suppressed AERP shortening. Bepridil might have a reverse electrical remodeling effect, at least for AERP shortening, because it showed slow recovery of AERP in the subacute phase of rapid atrial pacing. (Circ J 2006; 70: 206 - 213).     

Effects of Cilazapril on atrial electrical, structural and functional remodeling in atrial fibrillation dogs

Background and purpose

The effects of angiotensin-converting enzyme inhibitor on long-term atrial electrophysiologic and structural remodeling are still unclear. The purpose of this study is to investigate the effects of Cilazapril on atrial electrical, structural, and functional remodeling in atrial fibrillation (AF) dogs induced by chronic rapid atrial pacing.

Methods

Twenty dogs were randomly divided into sham-operated group (n = 6), control group (n = 7), and Cilazapril group (n = 7). One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium. A pacemaker was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in control group and Cilazapril group were paced at 400 beats per minute for 6 weeks. The dogs in Cilazapril group received Cilazapril (0.5 mg•kg⁻¹•d⁻¹) 1 week before rapid atrial pacing until pacing stop. Before and after 6-week rapid atrial pacing, atrial effective refractory period (AERP) at 8 sites, AERP dispersion, intraatrium conduction time, inducibility, and duration of AF were measured. Transthoracic and transesophageal echocardiographic examinations included left atrium (LA) maximal volume, LA minimal volume, LA ejection fraction, left atrial appendage (LAA) maximal volume, LAA minimal volume, LAA ejection fraction, LAA maximal forward flow velocity, and LAA minimal backward flow velocity were performed. Atrial collagen volume fraction was analyzed by Masson staining.

Results

After 6-week rapid atrial pacing, although there was no significant difference in AERP shortening and AERP rate adaptation reduction between the control group and the Cilazapril group, the inducibility and duration of AF were found to be dramatically lower in the Cilazapril group than those in the control group (AF inducibility, 65.7% vs 95.7%, P < .05; AF duration, 531.5 ± 301.2 vs 1432.2 ± 526.5 s, P < .01).The post-tachycardia intraatrium conduction times after 6 weeks with Cilazapril were significantly shorter than those in the control group. Cliazapril could partially prevent AERP dispersion increase induced by chronic rapid atrial pacing. Compared with the control group, the LA and LAA volumes were significantly smaller; LA ejection fraction, LAA ejection fraction, LAA maximal forward flow velocity, and LAA minimal backward flow velocity were dramatically higher in the Cilazapril group. The Cilazapril group had a significantly lower percentage of interstitial fibrosis than the control group.

Conclusions

Cilazapril can suppress structural and functional remodeling and prevent the induction and promotion of AF in chronic rapid atrial pacing dogs.     

Inducibility of atrial fibrillation caused by acute increase of atrial pressure in rat diseased heart with chronic atrial dilation

Although acute atrial dilation facilitates the induction of atrial fibrillation (AF) in the normal heart, little is known about whether the induction of AF due to acute atrial dilation increases in the diseased heart. To clarify this, we compared the inducibility of AF by an acute increase of atrial pressure with and without chronic atrial dilation induced by volume- and pressure-overload in rats. Eight weeks after creating abdominal aortocaval shunt and aortic constriction rats (LVH rats, n = 8) or sham rats (n = 8), the hearts were perfused in Langendorff's manner. Right atrial (RA) pressure was increased from 2 cm H2O to 10 cm H2O by the height of the reservoir. Inducibility of AF was evaluated by 5 times burst pacing from the right atrium, and mean cycle length of AF (CL) and the atrial effective refractory period (AERP) were also measured. The inducibility of AF increased from 5 ± 3% at 2 cm H2O to 50 ± 5% at 10 cm H2O RA pressure in sham rats (P < 0.01), but not in LVH rats (20 ± 7% to 25 ± 6%, NS). Mean CL and AERP in LVH rats were longer than those in sham rats. In addition, the AERP decreased with an increase in RA pressure from 2 cm H2O to 10 cm H2O in sham rats, but not in LVH rats. The inducibility of AF caused by an acute increase of RA pressure did not increase in the diseased heart, suggesting that electrophysiological remodeling may play a role, at least in a compensated state, for the prevention of AF due to an acute increase of atrial pressure.     

左旋卡尼汀对犬心房急性电重构的影响

目的观察左旋卡尼汀（L-carn itine,L-CN）对犬心房颤动（房颤）所引发心房急性电重构的预防作用。方法12只犬随机分为L-CN组和生理盐水对照组。以800次/m in的频率快速起搏右心房1 s以诱发短阵房颤,在恢复窦性心律即刻重复发放刺激以维持房颤2 h。观察各组房颤前后不同时间段的右心房有效不应期（AERP）、AERP的频率适应性及右心房内传导速度（CV）的变化。结果房颤后盐水组AERP显著缩短（P<0.05）,L-CN组房颤前后AERP无显著缩短;盐水组的AERP的频率适应性显著下降（P<0.05）,L-CN组该指标无显著变化;房颤前后两组间右心房内CV无明显改变。结论L-CN能够有效防止房颤诱发的心房急性电重构。     

犬急性心房颤动电重构现象的实验研究

目的 观察短阵心房颤动(房颤)的电重构现象及其恢复过程，探讨电重构与房颤再发及维持的关系。方法 15只健康成年犬于左、右心房外膜7个部位缝合双极记录电极，自心耳给予600次／min起搏诱发2h房颤，其中5只犬每间隔10min测量左、右心耳的心房有效不应期(AERP)，观察其恢复过程；另10只犬在房颤前后分别测量在起搏周长350ms、250ms、200ms时7个部位的AERP并记录电生理检查时房颤的诱发率及其持续时间。结果 2h房颤后心房各点AERP显著缩短，对心率适应不良，AERP离散度增高，继发性房颤诱发率增高、持续时间延长。AERP缩短可持续30min，60-80min后恢复。左心耳AERP恢复过程慢于右心耳。可诱发房颤的部位AERP更短，与继发性房颤的平均持续时间呈显著性负相关。可诱发房颤的心房其AERP离散度明显增高，但与继发性房颤的持续时间无关。AERP心率适应不良部位继发性房颤的诱发率高于生理性AERP心率适应性部位。低位右心房及左心耳部位的期前兴奋易于诱发房颤。结论 2h诱发的房颤足以使健康心房发生类似持续性房颤的电重构，电重构使房颤易于再发。AERP离散度与房颤的诱发有关，AERP缩短与房颤的持续性有关，房性早搏的发生部位与房颤的易患性有关。     

Mind the model: effect of instrumentation on inducibility of atrial fibrillation in a sheep model

INTRODUCTION: Atrial electrical remodeling, shortening of the atrial effective refractory period (AERP) underlying atrial fibrillation (AF) has been described in different animal models. However, there remains some controversy regarding the time course of this electrical remodeling and the need for secondary factors in the development of AF. We investigated the effect of instrumentation on the inducibility of AF. We hypothesized that epicardial instrumentation could be a confounding factor that accelerates the development of AF. METHODS AND RESULTS: Thirty sheep were rapidly atrially paced at 600 beats/min for 15 weeks: 15 were endocardially instrumented and paced (endo), and 15 were both endocardially and epicardially instrumented. Six of these animals were endocardially paced (sham) and 9 were epicardially paced (epi). The underlying rhythm was determined at regular intervals, and electrophysiologic study was performed. AF developed significantly faster in the epi group. After 3 weeks of pacing, the cumulative incidence of sustained AF (>1 hour) already was 70% in this group versus only 14% and 20% in the endo and sham groups, respectively. After 15 weeks of pacing, this difference was no longer evident. Baseline AERP and minimal AERP, reached before the development of AF, were not significantly different in the three groups. Epicardial instrumentation (epi and sham) increased baseline left and right atrial pressures, but only epicardial stimulation (epi) led to early development of AF. CONCLUSION: In this sheep model of AF, the experimental setup is a major determinant of the inducibility of AF. Not epicardial instrumentation per se but epicardial stimulation accelerated the development of AF. Different animal models     

Differences in organization between acute and chronic atrial fibrillation in dogs

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.     

心房电重构与房颤关系的基础研究

目的检查观测心房电生理改变与房颤（AF）发生和持续的关系,探讨心房电重构与房颤的内在联系。方法健康成年杂种犬14只（雌雄不拘,体重10．0～12．5kg）,随机分为2组：对照组（A组）和起搏组（B组）。右侧开胸将电极置于右心房,以400次／min的频率快速起搏右心房（A组只手术不起搏）,分别于实验开始及起搏6h后对每只犬进行电生理检查,测定心房有效不应期（AERP）。起搏开始及起搏后测定burst刺激诱发房颤的频率和持续时间。结果A组在整个时间内AERP无变化,B组心房快速起搏后,AERP明显缩短。A、B两组起搏前房颤的频率和持续时间差异无统计学意义。A组起搏前、后房颤的频率和持续时间无变化,B组心房快速起搏后房颤的频率增多,持续时间延长。结论快速心房起搏可以引起心房有效不应期缩短,即心房电重构。心房电重构造成的心房有效不应期等电生理变化促进了房颤的发生和维持,是心房电重构与房颤关系的基础。     

夹竹桃麻素对兔心房电重构的影响

目的探讨烟酰胺腺嘌呤二核苷酸磷酸氧化酶抑制剂夹竹桃麻素对兔心房急性电重构的预防作用。方法选择新西兰白兔18只,随机分为对照组、心房快速起搏组和夹竹桃麻素+心房快速起搏组(夹竹桃麻素组),每组6只。对照组和心房快速起搏组术前生理盐水3 ml/(kg·d)灌胃3 d,夹竹桃麻素组予30 mg/(kg·d)药物灌胃3d。对照组术中不行心房快速起搏,心房快速起搏组与夹竹桃麻素组术中以最快的能维持心房1:1起搏的频率(500～600/min)给予快速刺激。分别在0、0.5、1.0、1.5、2.0、2.5和3.0 h时,测量基础刺激周长分别为200 ms和1 50 ms的右心房有效不应期(atrial effective rcfractory period,AERP),分析AERP频率适应性的变化,并记录心房颤动(房颤)的诱发情况。结果对照组和夹竹桃麻素组AERP_(200)和AERP_(150)无明显变化,心房快速起搏组AERP_(200)和AERP_(150)与心房快速起搏时间呈负相关(r=—0.650,P<0.01;r=—0.498,P<0.01);对照组和夹竹桃麻素组AERP频率适应性指标无明显变化,心房快速起搏组AERP频率适应性与心房快速起搏时间呈负相关(r=一0.341,P<0.05);心房快速起搏组和夹竹桃麻素组的房颤诱发率分别为66.67%和16.67%,平均房颤持续时间分别为37.75 min和0.67 min,差异有统计学意义(P<0.05)。结论夹竹桃麻素能够减缓心房电重构的发生、发展,降低房颤的持续时间。     

Is There an Optimal Pacing Site to Prevent Atrial Fibrillation?: An Experimental Study in the Chronically Instrumented Goat

INTRODUCTION: Atrial pacing can reduce the number of recurrences of atrial fibrillation (AF). It is unclear the extent to which this effect is determined by the site(s) of pacing. METHODS AND RESULTS: In six electrically remodeled goats (24-hour AF), the window of inducibility of AF was determined by applying premature stimuli (S1-S2) at the right (RA) or left (LA) atrium (baseline values). Determination of the window of inducibility of AF at RA and LA was repeated during preventive pacing at four sites: RA, LA, Bachmann's bundle (BB), and RA+LA (biatrial). Mapping was used to elucidate the mechanisms of prevention of AF. At baseline, the window of inducibility of AF was 49 +/- 9 msec at RA and 45 +/- 17 msec at LA. Initiation of AF was associated with conduction block of the premature beat at BB. Preventive pacing at BB markedly shortened the window of inducibility of AF at RA (25 +/- 11 msec) and LA (17 +/- 8 msec, P < 0.01). Pacing at RA only shortened the window of inducibility of AF at LA (23 +/- 9 msec, P < 0.01), whereas pacing at LA only shortened the window of inducibility of AF at RA (23 +/- 11 msec, P < 0.01). Biatrial pacing failed to shorten the window of inducibility of AF both at RA and LA. Prevention of AF by pacing was due to prolongation of the premature interval at BB. CONCLUSION: In the caprine model of AF, BB is a critical area of conduction of premature beats and initiation of AF. Pacing at BB can prevent but not completely abolish the initiation of AF by single premature beats (shortening of the window of inducibility). Prevention of AF by pacing is based on prolongation of the premature interval at BB, thus preventing conduction block and reentry. In general, the optimal site for preventive pacing is close to the area of block and remote from the origin of premature beats.     

Chronic atrial dilation, electrical remodeling, and atrial fibrillation in the goat.

OBJECTIVES: This study was designed to investigate the mutual effects of chronic atrial dilation and electrical remodeling on the characteristics of atrial fibrillation (AF). BACKGROUND: Both electrical remodeling and atrial dilation promote the inducibility and perpetuation of AF. METHODS: In seven goats AF was induced during 48 h by burst pacing, both at baseline and after four weeks of slow idioventricular rhythm (total AV block). Atrial size and refractory period (AERP) were monitored together with the duration and cycle length of AF paroxysms (AFCL). After four weeks of total atrioventricular (AV) block, the conduction in both atria was mapped during AF. Six non-instrumented goats served as controls. RESULTS: At baseline, AF-induced electrical remodeling shortened AERP and AFCL to the same extent (from 185 +/- 9 ms to 149 +/- 14 ms [p < 0.05] and from 154 +/- 11 ms to 121 +/- 5 ms [p < 0.05], respectively). After four weeks of AV block the right atrial diameter had increased by 13.2 +/- 3.0% (p < 0.01). Surprisingly, in dilated atria electrical remodeling still shortened the AERP (from 165 +/- 9 ms to 132 +/- 15 ms [p < 0.05]) but failed to shorten the AFCL (140 +/- 19 ms vs. 139 +/- 11 ms [p = 0.98]). Mapping revealed a higher incidence of intra-atrial conduction delays during AF. Histologic analysis showed no atrial fibrosis but did reveal a positive correlation between the size of atrial myocytes and the incidence of intra-atrial conduction block (r = 0.60, p = 0.03). CONCLUSIONS: In a goat model of chronic atrial dilation, AF-induced electrical remodeling was unchanged. However, AFCL no longer shortened during electrical remodeling. Thus, in dilated atria a wider excitable gap exists during AF, probably caused by intra-atrial conduction defects and a higher contribution of anatomically defined re-entrant circuits.     

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.     

普罗帕酮在短期电重构后山羊心房的抗心律失常作用研究

为研究普罗帕酮对短期电重构后清醒山羊心房的电生理特性的影响,探讨其抗心律失常作用的可能机制,在7只山羊的左房游离壁外膜缝合4对电极,经皮下隧道将电极导线引至颈部皮肤外。术后2周测量不同基础刺激周长(BCL)时的心房有效不应期(AERP)、BCL为200ms时的心房传导速度(CV)并计算心房波长(WL)。心房快速刺激维持心房颤动(简称房颤)6h后静脉滴注(简称静滴)生理盐水,重复上述指标测量。2天后,在房颤6h后静滴普罗帕酮,重复上述测量。结果:①在基础状态下,AERP表现出频率适应性;②6h的房颤后,在静滴生理盐水时,AERP的频率依赖特性丧失。BCL为200ms时,AERP及WL均缩短,CV变化不显著;③在静滴普罗帕酮时,AERP显示使用依赖特性。BCL为200ms时,与基础状态时比较,AERP延长,CV及WL缩短;但与静滴盐水时相比,WL无明显变化。结论:在经过6h的电重构后,普罗帕酮使AERP表现为使用依赖特性。快速心房刺激时,普罗帕酮使AERP明显延长,CV明显缩短。     

Electrical Remodeling and Atrial Dilation During Atrial Tachycardia are Influenced by Ventricular Rate: Role of Developing Tachycardiomyopathy

INTRODUCTION: Atrial fibrillation (AF) and congestive heart failure (CHF) are two clinical entities that often coincide. Our aim was to establish the influence of concomitant high ventricular rate and consequent development of CHF on electrical remodeling and dilation during atrial tachycardia. METHODS AND RESULTS: A total of 14 goats was studied. Five goats were subjected to 3:1 AV pacing (A-paced group, atrial rate 240 beats/min, ventricular rate 80 beats/min). Nine goats were subjected to rapid 1:1 AV pacing (AV-paced group, atrial and ventricular rates 240 beats/min). During 4 weeks, right atrial (RA) and left ventricular (LV) diameters were measured during sinus rhythm. Atrial effective refractory periods (AERP) and inducibility of AF were assessed at three basic cycle lengths (BCL). After 4 weeks of rapid AV pacing, RA and LV diameters had increased to 151% and 113% of baseline, whereas after rapid atrial pacing alone, these parameters were unchanged. Right AERP (157+/-10 msec vs 144+/-16 msec at baseline with BCL of 400 msec in the A-paced and AV-paced group, respectively) initially decreased in both groups, reaching minimum values within 1 week. Subsequently, AERP partially recovered in AV-paced goats, whereas AERP remained short in A-paced goats (79+/-7 msec vs 102+/-12 msec after 4 weeks; P < 0.05). Left AERP demonstrated a similar time course. Inducibility of AF increased in both groups and reached a maximum during the first week in both groups, being 20% and 48% in the A-paced and AV-paced group, respectively. CONCLUSION: Nature and time course of atrial electrical remodeling and dilation during atrial tachycardia are influenced by concurrent high ventricular rate and consequent development of CHF.