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.     

Reverse-remodeling effects of angiotensin II type 1 receptor blocker in a canine atrial fibrillation model.

BACKGROUND: The reverse-remodeling effect of angiotensin II type 1 receptor blocker (ARB) on atrial fibrillation (AF) is unclear. METHODS AND RESULTS: Sustained AF was induced in 20 dogs by 4-week rapid atrial pacing. The AF duration, atrial effective refractory period (AERP) and intra-atrial conduction time (CT) were measured every 2 weeks. After 4-week pacing, dogs were randomly assigned to control (n=10) and ARB (olmesartan; n=10) groups. Olmesartan was administered orally (3 mg.kg(-1).day(-1)) after pacing was terminated, and continued for the 4-week recovery period. After 4-week pacing, AERP shortening, CT prolongation and AF maintenance were not significantly different between the 2 groups. During the recovery, AERP recovered to baseline in both groups. CT remained prolonged in the control group during the recovery, but recovered to baseline in the olmesartan group. The mean AF duration in the olmesartan group after 4-week-recovery was significantly shorter than that in the control group (58+/-20 vs 1,337+/-226 s, p<0.001). Olmesartan significantly decreased interstitial fibrosis compared with the control group (9+/-1% vs 15+/-1 at the right atrial appendage, p<0.001). CONCLUSION: Olmesartan has a reverse-remodeling effect on AF-induced structural changes, indicating that it may be useful for preventing AF recurrence after the termination of sustained AF.     

n-3 polyunsaturated fatty acids prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model

Objective

It has been recently reported that atrial fibrillation (AF) is associated with inflammation and inflammatory cytokines, and n-3 polyunsaturated fatty acids (PUFAs) might be of anti-inflammatory effects. This study was to evaluate the anti-inflammatory effect of PUFAs on AF in a canine sterile pericarditis model.

Methods

20 dogs were randomly assigned to two groups: control group (10 dogs) and PUFA treatment group (10 dogs), in which sterile pericarditis was created by open-chest operation. PUFAs were administered orally (2 g/day) 4 weeks before the operation till the end of the study. Before and 2 days after the operation, CRP, IL-6, TNF-α levels, the inducibility and maintenance of AF, the atrial effective refractory period (AERPs), and intra-atrial conduction time were determined.

Results

Before the operation, there were no significant differences in any of the parameters between the two groups. On the second postoperative day, the PUFA group had a lower CRP level (7.6 ± 0.5 vs. 11.7 ± 1.3 mg/dl, P < 0.0001), a lower IL-6 level (112.0 ± 37.3 vs. 142.0 ± 19.6 pg/ml, P < 0.01), a lower TNF-α level (83.3 ± 8.5 vs. 112.4 ± 8.2 pg/ml, P < 0.0001), a less AF inducibility (percentage of burst attempts leading to AF episodes: 11 ± 7.4 vs. 28 ± 10.3, P < 0.001) and maintenance [median AF duration: 1105 s (655.8-1406.5) vs. 2516.5 s (1187-3361), P < 0.05], a longer AERP (133.4 ± 4.1 vs. 129.8 ± 4.3 ms, P < 0.05), and a shorter intra-atrial conduction time (46.6 ± 4.4 vs. 51.9 ± 4.8 ms, P < 0.05) than the control group.

Conclusions

Dietary n-3 PUFA supplementation attenuates the inducibility and maintenance of AF in the sterile pericarditis model by reducing the production of proinflammatory cytokines.     

Prednisone prevents inducible atrial flutter in the canine sterile pericarditis model

Background: Atrial fibrillation (AF) and atrial flutter (AFL) are common following cardiac surgery and are associated with significant morbidity. We tested the hypothesis that suppression of the inflammatory response with steroids would significantly modify the inducibility of postoperative AF/AFL in the canine sterile pericarditis model.
Methods: Twenty-three dogs were studied daily from creation of pericarditis to the fourth postoperative day: 11 dogs were treated with oral prednisone (PRED) starting 2 days preoperatively until the end of the study; 12 dogs were controls (CON). EP testing was performed daily using epicardial electrodes placed at initial surgery. High-resolution (404 sites) epicardial mapping was performed during the terminal study. Baseline and daily CRP levels were obtained in all dogs.
Results: Sustained AFL was absent in PRED (0%) versus CON dogs (91%; P < 0.001); AF induced in the early postoperative course in PRED dogs was of very short CL (mean 66 ms). Tissue inflammation was significantly attenuated in PRED dogs. Thresholds were lower in PRED versus CON dogs, significantly so on postoperative day (POD) 3. There was a trend toward lower ERPs in the PRED group at all CLs. CRP levels were markedly reduced in PRED versus CON dogs (peak CRP 78 ± 7 mg/L vs 231 ± 21 mg/L, P < 0.001), and returned to baseline in PRED dogs by POD 4, correlating with a virtual absence of sustained arrhythmia. During open chest mapping studies on POD 4, PRED dogs showed only nonsustained AF/AFL.
Conclusions: Prednisone eliminated postoperative AFL, affected all EP parameters studied, and attenuated the inflammatory response associated with pericarditis.     

Antiarrhythmic effects of JTV-519, a novel cardioprotective drug,on atrial fibrillation/flutter in a canine sterile pericarditis model

Effect of JTV-519 on AF. INTRODUCTION: A new cardioprotective drug, JTV-519, blocks Na+ current and inwardly rectifying K+ current and inhibits Ca2+ current. However, its role in atrial electrophysiology is unknown. We investigated the antiarrhythmic effects of JTV-519 on atrial fibrillation/flutter in the canine sterile pericarditis model. METHODS AND RESULTS: In nine dogs with sterile pericarditis, 38 episodes of sustained (>30 sec) atrial fibrillation (8 dogs) and 24 episodes of sustained atrial flutter (7 dogs) were induced by rapid atrial pacing. When atrial fibrillation or atrial flutter was sustained >15 minutes, it was cardioverted and reinduced. The inducibility of atrial fibrillation/flutter, the atrial effective refractory period, and the intra-atrial conduction time were compared before and after the continuous infusion of JTV-519 (0.03 mg/kg/min). JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). In contrast, atrial flutter was still inducible in 4 dogs after JTV-519 (from 2.7 +/- 2.5 to 1.6 +/- 2.1, P = NS). JTV-519 significantly prolonged effective refractory period (from 123 +/- 18 to 143 +/- 14 msec, from 127 +/- 18 to 151 +/- 12 msec, and from 132 +/- 13 to 159 +/- 9 msec at basic cycle lengths of 200, 300, and 400 msec, respectively, P < 0.01), but it did not affect the intra-atrial conduction time (from 47 +/- 11 msec to 48 +/- 11 msec, P = NS). CONCLUSION: JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.     

Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation

The purpose of the present study was to evaluate the effect of angiotensin II type 1 receptor (AT1R) antagonist on chronic structural remodeling in atrial fibrillation (AF). BACKGROUND: We previously reported that an AT1R antagonist, candesartan, prevents acute electrical remodeling in a rapid pacing model. However, the effect of candesartan on chronic structural remodeling in AF is unclear. METHODS: Sustained AF was induced in 20 dogs (10 in a control group and 10 in a candesartan group) by rapid pacing of the right atrium (RA) at 400 beats/min for five weeks. Candesartan was administered orally (10 mg/kg/day) for one week before rapid pacing and was continued for five weeks. The AF duration, atrial effective refractory period (AERP) at four sites in the RA, and intra-atrial conduction time (CT) from the RA appendage to the other three sites were measured every week. RESULTS: The mean AF duration in the control group after five weeks was significantly longer than that with candesartan (1,333 +/- 725 vs. 411 +/- 301 s, p < 0.01). The degree of AERP shortening after five weeks was not significantly different between the two groups. The CT from the RA appendage to the low RA after five weeks with candesartan was significantly shorter than that in the control (43 +/- 14 vs. 68 +/- 10 ms, p < 0.05). The candesartan group had a significantly lower percentage of interstitial fibrosis than the control group (7 +/- 2% vs. 16 +/- 1% at the RA appendage, p < 0.001). CONCLUSIONS: Candesartan can prevent the promotion of AF by suppressing the development of structural remodeling.     

Antiarrhythmic Efficacy of a New Class III Antiarrhythmic Drug RG-2.

We studied effects of a new class III antiarrhythmic drug RG-2 in a canine model of vagally-mediated atrial fibrillation (AF). RG-2 was intravenously infused to anesthetized open-chest dogs in progressive doses (5, 10, 20 and 40 mg/kg, n=6) during vagally-induced AF. RG-2 significantly dose-dependently increased atrial effective refractory period (AERP) with and without vagal stimulation, but did not change conduction velocity. Five mg/kg terminated vagally-induced AF in 4 of 6 dogs but did not prevent AF reinduction. However, additional doses of drug 20 and 40 mg/kg successfully terminated AF in 100% as well as prevented AF reinduction in 50% and 72% of cases, respectively. Activation mapping (224 epicardial electrodes) showed that under drug influence there was gradual reduction of wavelet number until termination of the reentrant excitation. AF cycle length increased before AF termination from 91+/-4 to 140+/-8 ms (p<0.01). These changes correlated with drug-induced increasing of AERP. In conclusion, the ability of RG-2 to terminate and prevent reinduction of experimental AF appears to be associated with a significant prolongation of the AERP.     

阿托伐他汀对犬心房及肺静脉电活动的影响

目的 观察阿托伐他汀对犬心房及肺静脉电活动的影响。方法 将实验动物犬随机分为对照组(n=7)和试药组(n=7),其中试药组于术前4周每天服用阿托伐他汀（2 mg/kg）直至术前结束。之后分别测各组犬心房及肺静脉不应期,并进行房颤的诱发。结果 试药组犬的心房各部位不应期均较对照组延长,频率适应性较对照组提高。在房颤的诱发中,试药组房颤的诱发率较对照组低。 结论 阿托伐他汀可有效改善犬的心房电活动,从而对房颤的发生及复发起到抑制作用。     

Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting

Atrial fibrillation (AF) is one of the most common postoperative arrhythmias in patients who undergo coronary artery bypass grafting (CABG). The aim of this study was to evaluate the effect of preoperative atorvastatin on postoperative atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass (CCABG). One hundred consecutive patients undergoing elective CCABG, without history of AF or previous statin treatment, were enrolled and randomly assigned to a statin group (atorvastatin 20 mg/d, n = 49) or a control group (placebo, n = 51) starting 7 days preoperatively. The primary endpoint was the occurrence of postoperative AF. C-reactive protein (CRP) levels were assessed in all selected patients before surgery and every 24 hours postoperatively until discharge from hospital. Atorvastatin significantly reduced the incidence of postoperative AF and postoperative peak CRP level versus placebo (18% versus 41%, P = 0.017; 129.3 ± 24.3 mg/L versus 149.3 ± 32.5 mg/L, P < 0.0001). Kaplan-Meier curves confirmed a significantly better postoperative atrial fibrillation-free survival in the statin group (χ(2) = 7.466, P = 0.006). Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF (OR = 0.235, P = 0.007), whereas high postoperative CRP levels were associated with increased risk (OR = 2.421, P = 0.015). Preoperative atorvastatin administration may inhibit inflammatory reactions to prevent atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass.     

Single site radiofrequency catheter ablation of atrial fibrillation: studies guided by simultaneous multisite mapping in the canine sterile pericarditis model

OBJECTIVES: To test the hypothesis that when activation of Bachmann's bundle (BB) is critical to the unstable reentrant circuits that maintain atrial fibrillation (AF) in the sterile pericarditis canine model, a lesion in BB would prevent induction of stable AF. BACKGROUND: One mechanism of induced AF in this model is multiple unstable reentrant circuits, which frequently include BB as part of the reentrant pathway. METHODS: Simultaneous multisite mapping studies during AF and after ablation of BB were performed by recording (384 to 396 electrodes) from both atria and the atrial septum during six induced AF episodes in six dogs with sterile pericarditis. Activation maps of AF (mean duration, 24 +/- 28 min) during 12 consecutive 100-ms windows were analyzed. RESULTS: During AF, multiple unstable reentrant circuits (mean, 1.2 +/- 0.2 per window; range, 1 to 4) were observed, 68% involving BB. Nonactivation zones (mean duration, 57 +/- 16 ms in the right atrium and 53 +/- 23 ms in the left atrium) observed during AF were reactivated by a wave front most often coming from the atrial septum via BB (right atrium, 62%; left atrium, 67%). After successful radiofrequency catheter ablation of the midportion of BB, AF >5 s was not induced in all dogs. Mapping studies of transient AF (< or =5 s) induced after ablation showed neither reentrant circuits nor wave fronts activating the right atrium via BB. CONCLUSIONS: In this AF model, catheter ablation of BB terminates and prevents the induction of AF by preventing 1) formation of unstable reentrant circuits that involve BB, and 2) activation of the atrial-free walls after a nonactivation period.     

Supervulnerable phase immediately after termination of atrial fibrillation

INTRODUCTION: Recent studies with the implantable atrial cardioverter have shown that atrial fibrillation (AF) recurs almost immediately after successful cardioversion in about 27% of cases. In the present study, we determined the electrophysiologic properties of the caprine atrium immediately after spontaneous termination of AF both before and after 48 hours of AF-induced electrical remodeling. METHODS AND RESULTS: In eight goats, atrial effective refractory period (AERP), intra-atrial conduction velocity, and atrial wavelength were measured during sinus rhythm both before (t = 0) and after 48 hours (t = 48) of electrically maintained AF (baseline). After baseline, a 5-minute paroxysm of AF was induced, during which the refractory period (RPAF) was determined. AERP, conduction velocity, and atrial wavelength also were measured immediately after spontaneous restoration of sinus rhythm (post-AF values). Both in normal and remodeled atria, immediately after AF, AERP and conduction velocity were markedly decreased compared with baseline (P < 0.01). In normal atria, post-AF AERP (107+/-14 msec) gradually prolonged from its AF value (114+/-17 msec) to its baseline value (138+/-13 msec). Conduction velocity decreased from 130+/-9 cm/sec to 117+/-9 cm/sec. After 48 hours of AF, AERP had shortened to 74+/-8 msec. RPAF was 89+/-9 msec. Surprisingly, immediately after termination of AF, AERP shortened further to 58+/-6 msec (P < 0.01). Post-AF conduction velocity decreased from 136+/-11 cm/sec to 122+/-10 cm/sec (P < 0.01). As a result, the post-AF atrial wavelength became as short as 7.1+/-1 cm. These changes were transient, and all parameters gradually returned to baseline within 1 to 2 minutes after conversion of AF. CONCLUSION: Due to a combined decrease in AERP and conduction velocity, marked shortening of the atrial wavelength occurs during the first minutes after conversion of AF. In electrically remodeled atria, this results in a transient ultrashort value of AERP (<60 msec) and atrial wavelength (7.1 cm). These observations imply a highly vulnerable substrate for reentry immediately after termination of AF. During this supervulnerable phase, both early and later premature beats reinitiated immediate recurrences of AF.     

Electrophysiological and antiarrhythmic effects of the novel antiarrhythmic agent AZD7009: a comparison with azimilide and AVE0118 in the acutely dilated right atrium of the rabbit in vitro.

AIMS: To compare the electrophysiological and antiarrhythmic effects of AZD7009, azimilide, and AVE0118 in the acutely dilated rabbit atria in vitro. METHODS AND RESULTS: In the isolated Langendorf-perfused rabbit heart, the atrial effective refractory period (AERP) and the inducibility of atrial fibrillation (AF) were measured at increasing concentrations of AZD7009 (0.1-3 microM), azimilide (0.1-3 microM), and AVE0118 (0.3-10 microM). In separate groups of atria, termination of sustained AF was assessed. In non-dilated atria, the AERP was 82+/-1.3 ms (mean+/-SEM) and AF could not be induced. Dilation significantly reduced the AERP to 49+/-1.0 ms (P<0.001) and 92% of the atria became inducible. Perfusion with AZD7009, azimilide, and AVE0118 concentration-dependently increased the AERP and reduced the AF inducibility. At the highest concentrations of AZD7009, azimilide, and AVE0118, AERP and AF inducibility changed from 50+/-4.5 to 136+/-6.6 ms and 80 to 0% (both P<0.001) from 51+/-3.0 to 105+/-9.9 ms (P<0.001) and 80 to 0% (P<0.01) and from 46+/-2.8 to 85+/-6.0 ms and 90 to 0% (both P<0.001). Restoration of sinus rhythm was seen in 6/6, 5/6, and 5/6 hearts perfused with AZD7009, azimilide, and AVE0118, respectively. CONCLUSION: In the dilated rabbit atria, AZD7009, azimilide, and AVE0118 concentration-dependently increased AERP, effectively prevented AF induction, and rapidly restored sinus rhythm.     

Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart

INTRODUCTION: Atrial dilation and rapid pacing reduce atrial effective refractory periods (AERPs), thereby increasing the susceptibility to sustained atrial fibrillation (AF) in Langendorff-perfused rabbit hearts. It is unclear whether similar pathophysiologic mechanisms are operative in short-term electrophysiologic changes caused by dilation and rapid pacing. Therefore, we analyzed whether both forms of short-term electrophysiologic changes are similarly affected by pharmacologic interventions acting on different potential mechanisms underlying these changes. METHODS AND RESULTS: Thirty Langendorff-perfused rabbit hearts underwent a protocol with stepwise increase of intra-atrial pressure from 0 to 12 cm H2O followed by 10 minutes of rapid pacing at 4 cm H2O. The protocol was repeated after addition of glibenclamide (10 micromol/L, n = 7), cariporide (1 micromol/L, n = 7), or verapamil (1 micromol/L, n = 9). In the basal state, increase of intra-atrial pressure from 0 to 12 cm H2O decreased AERPs from 85 +/- 11 to 55 +/- 9 msec (P < 0.01), rapid pacing at low intra-atrial pressure (4 cmH2O) decreased AERP to a similar extent, from 81 +/- 11 to 60 +/- 10 (P < 0.01). At higher intra-atrial pressure, decrease of AERP was more pronounced (10 cm H2O: 37 +/- 2 msec) (n = 7). Addition of verapamil decreased basal AERP from 86 +/- 10 msec to 68 +/- 11 msec (P < 0.05). Short-term electrophysiologic changes due to atrial dilation were abolished; changes due to rapid pacing were reduced but still present. Glibenclamide and cariporide had no significant effect. CONCLUSION: Langendorff-perfused rabbit heart is a suitable model for studying short-term electrophysiologic changes due to both rapid pacing and atrial dilation. AERPs are shortened to a similar extent by both mechanisms, whereas a combination of the two leads to more pronounced AERP reduction. Calcium overload plays a crucial role in short-term electrophysiologic changes caused by atrial dilation, whereas atrial ischemia or acidosis has no significant impact.     

心力衰竭犬心房电生理特性的研究

为观察心力衰竭 (简称心衰 )犬心房肌电生理特性的改变 ,探讨充血性心衰时心房颤动 (AF)发生机制。选择14只犬随机分为起搏组 (n =7)和假手术组 (n =7) ,在左、右房各缝植 4对电极 ,电极尾端经皮下由犬背部穿出。假手术组犬埋置起搏器后不起搏。起搏组犬置入实验用VOO型起搏器快速心室起搏 (2 2 0次 /分 ) 6周 ,建立心衰犬模型 ,分别于起搏前、起搏 6周后 ,测定心房有效不应期 (AERP)、AERP离散度 (AERPd)、房内和房间传导时间及心房肌传导速度 ,记录AF诱发情况。结果 :①假手术组犬术前与术后比较 ,心功能和心房电生理特性均无明显变化。②心室快速起搏 6周犬AERP较起搏前略延长 ,但差异无显著性。起搏 6周犬AERPd较起搏前明显增大 (4 0 .4±15 .6msvs 2 2 .6± 10 .2ms,P <0 .0 5 )。与起搏前比较 ,起搏 6周犬房内及房间传导时间明显延长 (CTRA5 4 .7± 7.2msvs 33.1± 9.5ms ;CTLA5 2 .3± 8.9msvs 31.7± 6 .3ms ;CTRA LA6 9.7± 8.2msvs 4 2 .8± 7.9ms,P均 <0 .0 5 ) ,心房肌传导速度显著减慢 (CVRA5 4 .8± 7.9cm/svs 90 .7± 8.4cm/s ;CVLA5 7.4± 9.6cm/svs 94 .6± 10 .2cm/s,P均 <0 .0 5 )。③心衰犬AF诱发率、诱发次数、AF持续时间较起搏前明显增加。假手术组犬术前、术后比较AF诱发情况无?     

去迷走神经效应对心房颤动作用的实验研究

目的探讨去迷走神经效应在心房颤动中的作用。方法将16只成年健康犬随机分成切除脂肪垫组和保留脂肪垫组,心外膜缝植动物起搏器后快速起搏犬心房,观察两组心房有效不应期（AERP）及其离散度（AERPd）、心房颤动诱发率、持续时间等。结果两组持续心房起搏6周后,起搏器停止工作0、3、7h,保留脂肪垫组AERP和AERPd分别为（115±19）ms、（126±24）ms、（132±19）ms和（440±55）ms、（480±47）ms、（40±69）ms,与起搏前比较差异均有统计学意义（P〈0．05）,与保留脂肪垫组比较差异均无统计学意义（P〉005）。保留脂肪垫组持续性心房颤动诱发率714％,持续时间（52±62）min,阵发性心房颤动持续时间明显延长,切除脂肪垫组未诱发出持续性心房颤动。结论去迷走神经可减少实验犬心房颤动诱发率及控制持续时间。     

Detection of hypertensive patients at risk for paroxysmal atrial fibrillation during sinus rhythm by computer-assisted P wave analysis.

OBJECTIVE AND METHODS: To determine whether hypertensive patients at risk for paroxysmal atrial fibrillation (AF) could be detected while in sinus rhythm, a computer-based 12-lead surface electrocardiogram was recorded in 50 hypertensive patients with history of paroxysmal AF (group A) and in 60 hypertensive patients without history of AF (group B). The maximum P-wave duration (P(maximum)), the minimum P-wave duration (P(minimum)), P-wave dispersion (Pdispersion = Pmaximum Pminimum), adjusted P-wave dispersion (APdispersion = Pdispersion/square root of the number of measurable leads), mean P-wave duration (mean P) and the standard deviation of the P-wave duration in all measured leads (SDP) were calculated. RESULTS: Pdispersion, APdispersion and SDP were significantly higher in group A than in group B (Pdispersion, 52 +/- 19 versus 41 +/- 15 ms, P< 0.001; APdispersion, 15.2 +/- 5.5 versus 11.9 +/- 4.6 ms, P< 0.001; SDP, 16 +/- 5 versus 13 +/- 5 ms, P < 0.001). P(minimum), mean P and left ventricle ejection fraction (LVEF) were significantly lower in group A than in group B (Pminimum, 79 +/- 18 versus 91 +/- 13 ms, P < 0.001; mean P, 108 +/- 18 versus 116 +/- 13 ms, P= 0.005; LVEF, 64 +/- 5 versus 69 +/- 8%, P< 0.001). Pminimum, Pdispersion, mean P, SDP, APdispersion and LVEF were found to be significant univariate predictors of paroxysmal AF, whereas only Pminimum (P< 0.001) remained a significant independent predictor of paroxysmal AF in the multivariate analysis. CONCLUSION: Hypertensive patients at risk for paroxysmal AF could be detected while in sinus rhythm by computer-assisted electrocardiographic P-wave analysis.     

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。     

Effect of electrical and structural remodeling on spatiotemporal organization in acute and persistent atrial fibrillation

INTRODUCTION: Atrial fibrillation (AF) may originate from discrete sites of periodic activity. We studied the effect of structural and electrical remodeling on spatiotemporal organization in acute and persistent AF. METHODS AND RESULTS: Atrial effective refractory periods (AERPs) were recorded from five different sites at baseline and after pacing in acute AF (n = 8 dogs) and persistent AF (n = 8). Four persistent AF dogs subsequently were cardioverted to sinus rhythm to allow AERP recovery. Periodicity was quantified by calculating power spectra on left atrial electrograms obtained from a 64-electrode basket catheter. Left atrial size was measured by intracardiac echocardiography and structural changes were assessed by electron microscopy. Mean AERPs decreased after pacing in acute (128 +/- 16 msec to 108 +/- 29 msec, P < 0.001) and persistent AF (135 +/- 16 msec to 104 +/- 24 msec, P < 0.0001). AERP recovery was established after 7 days of sinus rhythm. Structural changes were mild in acute AF, severe in persistent AF, and remained severe after AERP recovery. A single dominant frequency was identified in 94% of acute AF bipoles, 57% in persistent AF, and 76% after AERP recovery. Average correlation coefficient was 0.82 among acute AF bipoles, 0.63 in persistent AF, and 0.73 after AERP recovery. CONCLUSION: Transition from acute to persistent AF is associated with loss of spatiotemporal organization. A single dominant frequency recruits the majority of the left atrium in acute AF. Persistent AF, however, is associated with structural remodeling and dominant frequency dispersion. Recovery of refractoriness only partially restores spatiotemporal organization, indicating a major role for structural remodeling in the maintenance of persistent AF.     

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。     

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.