左旋卡尼汀对犬心房急性缺血诱发电生理变化的影响

目的观察左旋卡尼汀（L—CN）对犬心房急性缺血时心房肌电生理改变及心房颤动（房颤）诱发率的影响。方法2003—2005年将解放军总医院的12只健康杂种犬随机分为L—CN用药组和生理盐水对照组。结扎右冠状动脉心房分支，造成心房肌局部缺血。观察各组缺血前后右心房不同部位的有效不应期（AERP）、右心房内传导速度（CV）的变化，计算右心房内心房激动波波长（WL）和房颤的诱发率并行心房肌病理学检查。结果（1）结扎右冠脉后盐水组缺血区心肌AERP均明显缩短；L—CN组右冠脉结扎后AERP无显著缩短。（2）冠脉结扎前后，两组右心房内CV均无明显改变。（3）结扎冠脉后，盐水组右心房内WL明显缩短；L—CN组的WL无显著变化。（4）盐水组结扎右冠脉后在不同时间段测量时均诱发房颤，L—CN组结扎冠脉后均未诱发房颤。（5）盐水组可见不同程度的心肌缺血，以冠脉结扎处近端为显著；L—CN组不同部位心肌均未见缺血变化。结论L—CN能够有效防止心肌缺血诱发的电生理变化，从而有效减少房颤的发作。     

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。     

射频消融第三脂肪垫对犬心房电生理参数及心房颤动诱发的影响

目的研究射频消融第三脂肪垫对犬心房电生理参数及心房颤动(房颤)诱发的影响。方法观察12只杂种犬在不同起搏周长下,消融第三脂肪垫前后心房不同部位有效不应期(AERP)、AERP离散度、AERP频率适应性,房颤诱发率及其诱发窗口的变化。结果与消融前相比,消融后心率变化差异无统计学意义(P>0.05)。随着起搏周长变短,AERP明显缩短,且差异具有统计学意义(均为P<0.05)。消融术后高位左心房、低位左心房、左心耳部位AERP明显缩短,高位右心房、低位右心房、右心耳部位AERP明显延长(均为P<0.05)。AERP离散度差异无统计学意义(P>0.05)。消融后不同测量部位的房颤诱发率均降低及房颤诱发窗口增宽。结论消融第三脂肪垫达到部分去迷走神经化,使左心房AERP缩短,同时使房颤诱发率降低及房颤诱发窗口增宽。     

迷走神经活动对心房电重构的影响

目的 研究迷走神经干预对心房电重构的影响.方法 24只杂种犬随机分为3组,为排除交感神经对心房电重构的影响,3组犬均应用美托洛尔阻断交感神经效应.A组10只犬快速心房起搏过程中无迷走神经干预,B组8只犬应用阿托品阻断迷走神经效应,C组6只犬在快速心房起搏过程中同时进行迷走神经刺激.在右心房(RA)、冠状静脉窦(CS)和右心室(RV)放置多极导管.通过RA电极导管进行600次/min心房起搏30 min构建急性心房电重构模型.在右心房快速起搏前后测量基础状态(无迷走神经刺激)和迷走神经刺激下的心房有效不应期(AERP)和心房颤动(房颤)易感窗口(VW).结果 A组犬右心房快速起搏后基础状态下及迷走神经刺激时的AERP较起搏前明显缩短(P＜0.05).B组犬右心房快速起搏后基础状态下及迷走神经刺激时的AERP较起搏前无明显变化(P＞0.05).C组犬右心房快速起搏后基础状态下及迷走神经刺激时的AERP较起搏前明显缩短(P＜0.05).A组及C组右心房快速起搏后AERP缩短值明显大于B组(P＜0.05),但A组及C组AERP缩短值差异无统计学意义(P＞0.05).迷走神经刺激下,B组犬在右心房快速起搏前后均较难诱发房颤(VW接近0),A组及C组犬右心房快速起搏后较起搏前容易诱发房颤(P＜0.05).结论 短期右心房快速起搏导致的心房电重构过程中伴随着迷走神经兴奋性增强.迷走神经兴奋性增强及迷走神经刺激加重心房电重构,导致房颤易感性增加.迷走神经阻滞能减轻心房电重构,降低房颤易感性.     

左旋卡尼汀在犬心房急性电重构中的抗氧化作用

目的: 探讨左旋卡尼汀(L-carnitine,L-CN)抑制犬心房颤动（房颤）时心房急性电重构的作用机制。方法: 18条成年杂种犬,随机分为生理盐水（NS）组、L-CN组和正常对照 (normal control,NC) 组。NS组予右心房600次/min快速起搏,诱发并维持房颤2 h;起搏前半小时静推生理盐水(300 mg/kg) ,继以液速50 ml/h维持静脉点滴2 h。L-CN组:右心房600次/min快速起搏,诱发并维持房颤2 h,起搏前半小时静推L-CN(300 mg/kg),继以2.5 mg/（kg·min）（液速50 ml/h）维持静脉点滴2 h。在不同观察时间点测定房颤前后电生理指标及静脉血氧化及抗氧化指标的变化。结果: ①房颤后NS组心房有效不应期（AERP）显著缩短(P<0.01),AERP的频率适应性显著下降(P<0.01);L-CN组房颤前后AERP和频率适应性无显著缩短;L-CN组较NS组房颤诱发率明显降低(P<0.05)。②NS组房颤时静脉血氧化应激产物较NC组显著增多(P<0.05),抗氧化指标显著下降(P<0.01)。③ L-CN组丙二醛（Malondialdehyd,MDA）生成显著减少(P<0.01),超氧化物歧化酶（superoxide dismutase,SOD）显著增加(P<0.05)。结论: L-CN对房颤时氧化应激及电重构有明显保护作用,这种保护机制可能通过清除自由基,抑制脂质过氧化而发挥作用。     

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。     

慢-快综合征心房电重构和逆向电重构现象的实验研究

目的：建立犬窦房结功能不良（SND）下心房快速刺激心房颤动（房颤）的模型，探讨缓慢心律失常下慢-快综合征发生的心房电重构和逆向电重构现象。方法：12只健康成年犬用甲醛损伤犬窦房结建立SND模型，于左、右心房外膜7个部位自身前后对照观察心房有效不应期（AERP）变化及离散度、房颤的诱发率及AERP的恢复过程。结果：SND和心房快速刺激可导致犬心房各部位AERP缩短，AERP离散度增高。心房快速刺激终止后，AERP逐渐恢复，且左心耳AERP恢复过程慢于右心耳。低位右心房及左心耳部位的期前兴奋更易诱发房颤。结论：SND可致心房各部位AERP缩短且程度不同，是SND时易发生房颤的电生理基础，SND本身引起的心房电重构是慢-快综合征发生的重要机制，心脏电学顿抑是重要的电生理学现象。     

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。     

交感神经对犬快速右心房起搏诱发阵发性心房颤动的影响

目的研究交感神经对犬快速右心房起搏所诱发的心房颤动(房颤)中的作用。方法选择杂种犬28只,随机分为4组:交感刺激组、交感离断组、异丙肾上腺素组(Iso组)、美托洛尔组(Met组),每组7只。各组分别于交感神经干预前后检测心房有效不应期(AERP)及快速右心房起搏的房颤诱发情况,观察各组交感神经干预对其的影响。结果与基础状态比较,交感刺激组和Iso组干预后AERP明显缩短(P<0.05),交感离断组和Met组AERP明显延长(P<0.01);Iso组房颤诱发率明显升高(P<0.01)。与交感刺激组和Met组比较,Iso组房颤诱发率明显升高(P<0.01)。随着AERP时程延长,房颤的诱发率逐渐下降,呈负相关线性趋势(r=-0.728,P=0.003)。结论交感神经活性与心房电重构有一定的联系,单纯刺激交感神经不能改变房颤的诱发频率,但交感神经递质可使房颤更易于诱发。     

风心病慢性房颤心外膜标测心房有效不应期的对比研究

目的:研究风心病慢性房颤的电生理特征。方法:对29例风心病伴或不伴慢性房颤的病人在行二尖瓣置换术时,采用心外膜标测技术测定左、右心房各部位的有效不应期(AERP)及右房内和房间的传导时间。结果:风心病慢性房颤组左、右心房AERP比窦性心律明显缩短(P<0.05),左、右心房各部分的AERF,之间有明显差异(P< 0.01),即存在明显离散性;慢性房颤组的右房和房间传导时间在转复为窦性心律和缩短刺激右房高位问期时均显著长于正常对照组(P<0.05)。结论:风心病慢性房颤心房各部位AERP的差异反映了其AERP的离散性,而AERP 的离散性在房颤的诱发和维持过程中起着重要作用。     

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。     

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.     

Effects of ryanodine receptors block on spontaneous initiation of atrial fibrillation in the intact canine heart

To study the possible role of intracellular Ca2+ overload in initiation of cholinergic-dependent atrial fibrillation (AF), we tested the effects of ryanodine in canine models of AF. In anesthetized open-chest dogs (n=10) AF was induced by two methods: (I) perfusion (9 ml/min) with normal Tyrode solution containing acetylcholine (ACh) into the sinus node artery (SNA) and (II) stimulation of the right vagal nerve (VS, 5 sec train). AF was induced in all dogs: by perfusion with ACh (3.7-/+1.5 mcM) into the SNA in 97-/+3% of attempts and by VS in 78-/+6% of attempts. Intravenous infusion of ryanodine (5 mg/kg) did not prevent induction of AF during ACh perfusion (84-/+5%, NS) but completely prevented the induction of AF by VS (4-/+3%, p<0.001). Atrial activation mapping (112 unipolar electrodes) did not show any significant differences between the beginning of ACh-dependent AF in control and after ryanodine treatment. Ryanodine significantly reduced both systolic and diastolic arterial pressures but had no effect on heart rate, atrial effective refractory period (AERP) and conduction velocity for one hour after infusion. Ryanodine, itself, did not exert antivagal activity, so after ryanodine treatment in the presence of VS (8 Hz) the reduction of AERP and the deceleration of heart rate were similar to that in control. These data suggest that ryanodine can suppress the initiation of AF induced by VS but not AF induced by ACh perfusion. We can conclude that the initiation of AF during ACh perfusion unlikely relates to triggering activity induced by intracellular Ca2+ overload. In addition, we suggest that besides ACh some 'unclear' ryanodine sensitive factor(s) contribute to the initiation of AF induced by VS.     

The pharmacological response of ischemia-related atrial fibrillation in dogs: evidence for substrate-specific efficacy

OBJECTIVE: Acute atrial ischemia produces a substrate for atrial fibrillation (AF) maintenance, but the response of this substrate to antiarrhythmic-drugs has not been defined. The present study assessed the effects of class 1-4 antiarrhythmic-drugs on the electrophysiological consequences of acute atrial ischemia, and compared effects in ischemic AF with those in vagal AF. METHODS AND RESULTS: Isolated atrial ischemia was created by ligating a right coronary artery branch perfusing the right atrial free wall. Experiments were performed in dogs treated with loading and maintenance doses of flecainide (class 1; n=5), nadolol (class 2, n=7), dofetilide (class 3, n=5), or diltiazem (class 4, n=7) prior to coronary artery occlusion. Dogs subjected to coronary occlusion without pre-treatment (n=10) served as controls. Coronary artery occlusion substantially increased AF duration, e.g. from 7+/-4 s (pre-ischemic baseline) to 876+/-245 s at 3 h of ischemia, and caused substantial ischemic zone conduction slowing. Diltiazem and nadolol prevented AF promotion (AF durations 12+/-8 s and 4+/-1 s at 3 h of ischemia respectively; each p<0.001 vs control) and suppressed ischemic conduction slowing. Flecainide and dofetilide failed to prevent ischemia-induced AF promotion (e.g. AF duration at 3-hour ischemia 779+/-417 and 801+/-414 respectively, p=NS vs control) and failed to alter ischemia-induced conduction slowing. A different pattern of response occurred with vagal AF: flecainide was highly effective in reducing vagal AF duration; dofetilide, diltiazem, and nadolol were ineffective. CONCLUSIONS: Beta-blockade and Ca(2+) antagonism suppress the arrhythmic consequences of acute atrial ischemia, whereas Na(+) channel or K(+)-channel block are ineffective. These results are relevant to understanding the effects of different classes of antiarrhythmic-drugs on AF occurring in coronary disease patients.