正常心肌与肥厚心肌跨室壁不应期离散度实验研究

目的：探讨在体犬正常心室肌以及肥厚心室肌三层之章否存在跨室壁的不应期离散。方法：采用特制电极直接测量在体三层心肌的不应期。结果：正常心肌三层之间的不应期呈均一性,没有显的不应期离散。同正常心肌相比,肥厚心肌三层不应期均有延长,而中层心肌延长的幅度最大,使得跨室壁的不应期离散度增大。采用突然的循环长度改变可使跨室壁的不应期离散度增大更加明显。结论：正常犬三层心肌之间不存在跨室壁的不应期梯度,而肥厚心肌中存在跨室壁的不应期离散。采用长－短间期和短－长间期刺激可使跨室壁的不应期离散度增大。     

胺碘酮对肥厚心肌钙调蛋白激酶活性的影响

目的观察口服胺碘酮对肥厚心肌细胞钙调蛋白激酶(CaMK)活性的影响,探讨胺碘酮抗心律失常的作用机制。方法30只家兔随机分为假手术组、心肌肥厚组和胺碘酮组,每组10只,喂养3个月,制备兔左室楔形心肌块。同步记录楔形心肌块容积心电图和内、外膜心肌细胞跨膜动作电位(TAP),程序电刺激诱发室性心律失常,并观察各组QT间期、跨室壁复极离散度(TDR)、早期后除极(EAD)和尖端扭转型室性心动过速(Tdp)的诱发率。利用放射免疫法测定心肌细胞CaMK活性。结果胺碘酮组和心肌肥厚组QT间期、内外膜心肌细胞TAP复极90%时程(APD90)和TDR均较假手术组明显延长(P<0.01),胺碘酮组QT间期和内、外膜心肌细胞APD90与心肌肥厚组相比进一步延长(P<0.05),但对TDR无明显影响。与假手术组比较,心肌肥厚组EAD和Tdp的发生率较假手术组明显升高(P<0.01),胺碘酮组EAD和Tdp的发生率较心肌肥厚组降低(P<0.05)。心肌肥厚组心肌细胞CaMK活性较假手术组明显升高,胺碘酮组CaMK活性较心肌肥厚组降低(P均<0.05)。结论胺碘酮抗心律失常的作用机制可能部分与抑制CaMK活性有关。     

缺血预适应对犬在体三层心肌单向动作电位和不应期的影响

探讨缺血预适应(IPC)抗急性缺血心律失常的部分电生理机制。12只犬随机分为对照组(n=6)和IPC组(n=6),采用特制电极记录和测量三层心肌单相动作电位(MAP)及有效不应期(ERP),测量并分析MAP时程(MAPD),MAPD跨室壁离散(TDR)及ERP跨室壁离散(TDE)。结果:对照组缺血时MAPD缩短,ERP延长且三层心肌延长的幅度不一致,IPC组缺血时MAPD缩短与ERP延长均不明显,两者相比具有显著差别(P<0.05)。两组三层心肌之间的MAPD变化一致,不存在TDR,对照组缺血时ERP变化明显不一致,TDE增大,与IPC组相比较具有显著差别(P<0.05或<0.01)。结论:IPC减少急性缺血时MAPD缩短、ERP延长及TDE,这可能是其抗心律失常的部分机制。     

胺碘酮急性和慢性给药对正常和肥厚心肌电生理作用的差别

目的研究胺碘酮对肥厚心肌与正常心肌急性和慢性电生理作用的差别。方法采用缩窄腹主动脉的SD大鼠为实验模型,4周后形成左室肥厚,应用酶解技术获得单个心室肌细胞;应用膜片钳技术检测内向电流INa、ICa-L和外向电流Ik、Ito、Ik1,应用多非利特阻滞Ikr,所测Ik代表Iks;急性实验采用不同浓度胺碘酮灌流心肌细胞,慢性试验采用胺碘酮100mg·kg-1·d-1灌胃4周。结果肥厚心肌细胞电重构特征为Ito、Ik、Iks、Ik1外向电流密度降低;胺碘酮对肥厚心肌急性电生理作用为INa、Iks阻滞强度大于正常心肌,但ICa-L阻滞弱于正常心肌;胺碘酮的慢性作用,正常心肌与肥厚心肌相似,表现Ito、Ik、Iks阻滞,对内向电流影响较小。结论胺碘酮对肥厚心肌细胞的急性和慢性电生理作用,均提示其有利于肥厚心肌的抗心律失常治疗。     

急性缺血时犬3层心肌单向动作电位时程和有效不应期变化

目的:探讨急性缺血对犬在体3层心肌的电生理影响。方法:将12只犬随机分为急性缺血组(6只)和假手术组(6只)。应用单向动作电位(MAP)技术和特制的复合电极同步记录MAP和测定有效不应期(ERP),并分析跨室壁复极离散(TDR)和跨室壁不应期离散(TDE)。结果:在急性缺血组,MAP时程从[(201·67±21·42)ms缩短至(169·50±13·81)ms,P<0·05],而ERP不同程度地延长,且TDE增大。在假手术组,MAP时程和ERP没有明显变化。2组3层心肌之间MAP时程是一致的,不存在TDR。结论:急性缺血时MAP时程缩短,但3层心肌之间没有差别,而ERP延长伴随TDE增大。这可能在急性缺血时心律失常的发生中扮演重要角色。     

预处理对缺血再灌注时心肌电生理的影响

目的探讨缺血预适应（IPC）对缺血/再灌注心律失常的影响及其机制。方法12只犬随机分为对照组（n=6）和IPC组（n=6）,采用特制电极记录技术,观察和测量三层心肌单相动作电位（MAP）及有效不应期（ERP）,分析室性心律失常发生率、MAP时程（MAPD）、MAPD跨室壁离散（TDR）及ERP跨室壁离散（TDE）。结果对照组6只中有4只发生室速/室颤,而IPC组6只中仅1只发生室速/室颤。对照组缺血时MAPD同步缩短,而ERP延长且三层心肌延长的幅度不一致,再灌注时逐步恢复。IPC组缺血时MAPD缩短与ERP延长均不明显,与对照组相比,具有显著差异（P<0.05）。各组三层心肌之间的MAPD是一致的。对照组缺血/再灌注时ERP明显不一致,TDE增大,而IPC组TDE小,两者相比较具有显著差异（P<0.05或P<0.01）。结论IPC减少缺血/再灌时MAPD、ERP的变化及TDE,这可能是其抗心律失常的部分机制。     

左室壁中层心肌起搏对缺血再灌注犬跨室壁复极离散的影响

目的研究心室壁中层(M层)起搏对缺血再灌注犬跨壁复极离散(TDR)的影响,探讨采用M层起搏技术防治TDR增大相关性心律失常的可行性。方法制作正常犬及缺血再灌注后犬左室楔形心肌组织块模型,观察心内、外膜及M层起搏时,各层心肌动作电位时程(APD)及TDR的变化。结果心室内、外膜和M层起搏,心肌各层APD无显著变化(P﹥0.05);在正常状态时,心外膜起搏时,心外膜与M层之间的传导时间(TM-Epi)(24.3±2.4ms)显著长于心内膜起搏(12.0±0.8 ms)或M层起搏(12.6±0.7 ms)时的TM-Epi(P﹤0.05)。M层起搏时,TDR较外膜起搏明显减小(34.9±5.4 ms vs 71.5±6.1 ms,P﹤0.01),与内膜起搏(35.9±5.4 ms)相比无显著差异(P﹥0.05)。缺血再灌注后,结果与正常状态时相似。心外膜起搏(32.3±5.8 ms)时,TM-Epi较M层起搏(15.1±2.9ms)或内膜起搏(15.3±2.8 ms)进一步延长(P﹤0.05)。M层起搏时,TDR较外膜起搏明显减小(63.3±13.3 msvs 111.1±17.7 ms,P﹤0.01),与内膜起搏(62.8±13.8 ms)相比无显著差异(P﹥0.05)。结论与心外膜起搏相比,M层起搏可有效减小TDR;但与心内膜起搏相比,无明显差别。     

奎尼丁与胺碘酮对犬心室复极和室颤阈值影响的比较

采用记录心外膜单相动作电位和电刺激技术观察口服奎尼丁或胺碘酮4周后的犬心室电生理参数的改变,以探讨奎尼丁和胺碘酮对犬心室电生理效应的影响。结果显示:奎尼丁和胺碘酮延长心室有效不应期分别达42.2%和51.9%(P 均<0.01),延长 Q-T 间期分别达58.1%和62.4%(P 均<0.01)。奎尼丁延长 QRS 时限达47.9%(P<0.01),其延长单相动作电位复极50%～90%Ⅱ寸程(MAPD_(50～90))较胺碘酮更显著(P<0.01),并使其复极离散度(MAPDd)增加105.9%(P<0.01),对室颤阈值(VFT)无显著影响。而胺碘酮延长 QRS 时限无统计学意义(P>0.05),对 MAPDd 无显著影响,提高 VFT 达52.0%(P<0.01)。实验表明胺碘酮能提高心室电稳定性而奎尼丁无助于心室电稳定性的提高。     

四氢巴马汀对在体犬跨室壁复极离散度的影响

从跨室壁复极离散度(TDR)的角度研究左旋四氢巴马汀(L-THP)的电生理作用。采用自制电极同步记录在体犬左室三层心肌细胞的单向动作电位(MAP),观察静脉注射L-THP前后动作电位时程(APD)、振幅(APA)、TDR及各层心肌有效不应期(ERP)的变化。结果:应用L-THP后三层心肌的动作电位复极90%的时程均延长(内、中、外层心肌分别为189.67±23.29msvs182.83±23.70ms、194.67±24.12msvs192.17±24.49ms和185.08±24.53msvs173.42±22.06ms,P均<0.01),内、外层心肌ERP显著增加(分别为164.54±20.53msvs159.08±20.08ms、161.60±21.28msvs150.99±18.93ms,P<0.01)、TDR降低(9.58±2.94msvs18.75±3.77ms,P<0.01),对APA无明显影响。结论:L-THP降低心室肌的TDR,延长心室内、外膜心肌细胞的ERP。     

胺碘酮、索他洛尔与d-索他洛尔对犬心室肌细胞电生理作用的实验研究

目的分析胺碘酮、索他洛尔与d-索他洛尔对犬心室肌细胞电生理作用.方法采用标准玻璃微电极技术,观察胺碘酮、d,l-索他洛尔(即索他洛尔)与d-索他洛尔对犬心室肌细胞动作电位时程(APD)及跨壁复极离散(TDR)的作用,以研究三种药物不同的促心律失常发生率的机制.结果胺碘酮(5μM)对心室壁三层细胞APD作用不一,使M细胞的APD90缩短,而内、外膜的APD90延长,TDR降低.索他洛尔(100μM)使心室壁三层细胞APD90均延长,对M细胞APD延长更明显,使TDR增加.d-索他洛尔(100μM)使心室壁三层细胞APD90均增加,但以M细胞APD90增加最为显著,而且随着d-索他洛尔诱发早期后除极、APD交替变异发生,而在心室肌内、外膜细胞则未见上述变化.结论胺碘酮、索他洛尔及d-索他洛尔三种药物的不同促心律失常作用与其对心室TDR的作用不同有关.     

尼非卡兰和胺碘酮对心房及肺静脉肌细胞动作电位影响的比较

目的比较尼非卡兰和胺碘酮对心房及肺静脉组织动作电位的影响,探讨尼非卡兰在房性心律失常中的作用。方法取15只大耳白兔右心房、左心房和肺静脉组织制成0.5 cm×1.5cm组织条,采用标准玻璃微电极技术,记录各部位组织动作电位和有效不应期,先基础台氏液灌注15 min后,测动作电位和有效不应期为对照组,随后分别用含2.13 mg/L尼非卡兰(尼非卡兰组)和含3.75 mg/L胺碘酮(胺碘酮组)的台氏液灌流15 min后,采用同样方法引发动作电位和测定有效不应期,比较各组动作电位时程和有效不应期。结果与对照组比较,尼非卡兰组和胺碘酮组左心房、右心房、肺静脉肌袖组织动作电位时程均显著延长,胺碘酮组左心房和肺静脉有效不应期显著延长(P<0.05,P<0.01)。结论尼非卡兰的延长心房和肺静脉肌袖组织动作电位时相及不应期的电药理作用与胺碘酮相近,可能是其治疗房性心律失常的基础。     

地尔硫(艹卓)、普罗帕酮和胺碘酮对短阵心房快速除极诱发的心房有效不应期变化的影响

目的　研究地尔硫、普罗帕酮和胺碘酮对短阵心房快速除极诱发的心房有效不应期(ERP)变化的影响。方法　 6 9例室上性心动过速消融成功后的自愿者 ,被随机分为对照组、地尔硫组、普罗帕酮组和胺碘酮组。以 4 0 0ms起搏周长 (PCL)分别对高位右心房、低位右心房、希氏束周围等部位进行S1S2 程序刺激 ,另以 3个不同PCL(35 0、4 0 0和 4 5 0ms)对右心耳进行S1S2 程序刺激 ,应用双极记录法测定各组在基础状态、心房快速除极前、后心房ERP和ERP频率自适应性 (ERP RA)的变化 ,同时观察心房快速除极后程序刺激过程中意外诱发继发性心房颤动 (AF)的情况。结果　基础状态下 ,各组 4 0 0ms周长下心房各部位ERP差异不显著 ;心房快速除极前 ,对照组和地尔硫组心房各部位ERP无明显改变 ,而普罗帕酮组和胺碘酮组心房各部位ERP均明显延长 ;心房快速除极后 ,地尔硫组心房各部位ERP较除极前无明显缩短 ,对照组、普罗帕酮组和胺碘酮组心房各部位ERP较除极前均明显缩短。对照组、普罗帕酮组和胺碘酮组心房快速除极后斜率均值较除极前明显下降 ,地尔硫组心房快速除极后斜率均值较除极前无明显变化。地尔硫组、普罗帕酮组和胺碘酮组心房快速除极后继发AF发生阵数明显低于对照组。结论　预先给予地尔硫可以阻止心     

Mechanisms of termination of supraventricular tachycardias by intravenous class III antiarrhythmic agents. A comparison of amiodarone and sotalol

The effects of amiodarone and sotalol were studied with programmed electrical stimulation of the heart in 19 patients with inducible tachycardia (AV nodal tachycardia: 10 cases, circus movement tachycardia: 9 cases). Amiodarone was administered intravenously at a dose of 300 mg over 2 min and sotalol at a dose of 1.5 mg kg-1 over 10 min. Both i.v. amiodarone and sotalol lengthened the transnodal conduction time, the effective refractory period of the AV node and the AV nodal Wenckebach cycle length. Only sotalol significantly lengthened the effective refractory periods of the right atrium and the right ventricle. Infused intravenously during tachycardia, amiodarone interrupted arrhythmia in five of six patients and sotalol in seven of ten cases. Tachycardia was stopped by blockade of the impulse into the AV node in three amiodarone patients and in five sotalol patients. In the remaining four cases, the weak link of the circuit was the accessory pathway. Thus i.v. sotalol exhibits electrophysiologic effects consistent with both class II and III activity, whereas the effects of i.v. amiodarone are the result of different activities throughout all areas of the cardiac tissue.     

Antiarrhythmic efficacy and electrophysiologic actions of amiodarone in patients with life-threatening ventricular arrhythmias: Potent suppression of spontaneously occurring tachyarrhythmias versus inconsistent abolition of induced ventricular tachycardia

The antiarrhythmic efficacy and the electrophysiologic effects of amiodarone were determined in 13 consecutive patients with symptomatic life-threatening ventricular arrhythmias resistant to conventional agents. Amiodarone was initially given in high doses (1000 to 1800 mg/daily); electrophysiologic effects including induction of ventricular tachycardia (VT) by programmed electrical stimulation (PES) was undertaken before and after a mean period of 28 (range 14 to 56) days of amiodarone therapy. Plasma drug levels determined by high pressure liquid chromatography were within the “therapeutic” range (0.92 to 11.99 mg/L). Antiarrhythmic efficacy was determined on the basis of the quantitative analysis of 24-hour Holter recordings. Amiodarone reduced heart rate (HR) (?17.6%, p < 0.001), lengthened PR interval (+15%, p < 0.05), AH interval (+19.8%, P < 0.01), and the QT_o by 13.3% (p < 0.01), without effect on the QRS or HV intervals. The atrial effective refractory period (ERP) increased by 31.3% (p < 0.001) and the ventricular ERP by 22.5% (p < 0.001); ERP of the AV node also increased but could not be determined in all patients because of the longer refractory period of the atrium. Before amiodarone, AV Wenckebach during atrial pacing developed at HR of 150 ± 13 bpm and at 117 ± 7.6 bpm during amiodarone therapy (p < 0.01). In all 13 patients, amiodarone reduced the total counts of premature ventricular beats (PVCs) by 95% to 98% and eliminated complex ventricular ectopic activity (VEA) and runs of VT. The effect has been sustained during a mean follow-up period of 12 months and there have been no symptoms. Before amiodarone was given, VT could be induced by PES in 12 of 13 patients (seven sustained, five nonsustained). On amiodarone, VT was provoked in four (three sustained, one nonsustained). Side effects have included photosensitivity, proximal muscle weakness, elevation of hepatic enzymes, halo vision, and corneal deposits but without impaired vision; these could be reduced in severity or avoided by reduction in drug dosage. These data indicate that amiodarone is highly potent in suppressing symptomatic life-threatening ventricular tachycardias (PVCs, VEA, $\text{VT}\text{VF}$) without always being able to prevent the induction of VT by PES of the heart. The drug can be used in this context without the need for invasive electrophysiologic studies.     

Effect of acute subendocardial ischemia on ventricular refractory periods

OBJECTIVES: To investigate the impact of acute subendocardial ischemia on the dispersion of ventricular refractory periods. METHODS: Acute subendocardial ischemia was induced in sheep by partial ligation of the left circumflex coronary artery and rapid pacing of the left atrium. The ventricular effective refractory period (ERP) was measured in five areas of the left ventricle by a programmed premature stimulation technique. RESULTS: The average ERP and ERP dispersion remained unchanged in the control group (n=5, P>0.05). In the study group (n=5), the ERP was shortened following subendocardial ischemia. ERP dispersion decreased significantly from 48+/-9 ms to 36+/-13 ms 30 min after the ischemia (P=0.02). There was neither spontaneous nor stimulation-induced ventricular arrhythmia after ischemia. CONCLUSION: Acute subendocardial ischemia leads to a homogenous reduction of ventricular ERP. This may partially explain why subendocardial ischemia is associated with a low incidence of ventricular arrhythmia.     

自主神经系统对在体犬跨室壁三层心肌不应期不均一性影响的研究

为探讨自主神经系统对在体犬跨室壁三层心肌细胞不应期离散度的影响 ,分别在基础和缺血状态下 ,在交感神经和迷走神经刺激的过程中 ,用程序刺激法测定健康家犬在体心外膜心肌、中层心肌和心内膜心肌的不应期。结果 :在基础状态下 ,交感神经刺激能缩短三层心肌细胞的不应期 ,中层心肌细胞的不应期缩短最明显 ,跨室壁三层心肌不应期的离散度由 3± 2ms增加到 18± 6ms(P <0 .0 1) ;迷走神经刺激能延长三层心肌的不应期 ,心内膜心肌增加明显 ,跨室壁不应期离散度由 3± 2ms增加到 9± 4ms(P <0 .0 5 )。在急性缺血状态下 ,交感神经刺激延长三层心肌细胞的不应期 ,其中中层心肌细胞的不应期增加最明显 ,与刺激前相比 ,跨室壁不应期离散度由 4± 3ms增加到 16± 4ms(P <0 .0 1) ;迷走神经刺激对三层心肌细胞的不应期影响较小 ,与刺激前相比 ,跨室壁不应期离散度无显著变化。结论 :在基础及缺血状态下 ,交感神经刺激均能增加跨室壁不应期离散度 ;迷走神经刺激对跨室壁不应期离散度无显著影响。     

迷走神经刺激对心力衰竭兔跨室壁离散度影响的研究

目的研究迷走神经刺激对心力衰竭兔跨室壁离散度的影响。方法用阿霉素制作兔心力衰竭模型,采用单相动作电位（MAP）记录技术分别记录10只正常兔和9只心力衰竭兔左心室心肌内、中、外膜3层的MAP,分别于刺激前、后记录MAP,测量90％的动作电位时限（MAPD90）,分析跨室壁复极离散度（TDR）的变化。结果在迷走神经刺激前,心力衰竭组与正常组比较,MAPD90有所缩短,TDR则明显增大（P〈0．05）;在迷走神经刺激前后的自身比较中,心力衰竭组和正常组MAPD90都有所延长,正常组TDR差异无统计学意义（P〉0．05）,心力衰竭组TDR差异有统计学意义（P〈0．05）。结论迷走神经刺激可使心力衰竭组的TDR减小,从而减少恶性室性心律失常的发生率。     

Effect of amiodarone in the Wolff-Parkinson-White syndrome

The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.     

Dose-dependent electrophysiologic effects of amiodarone in the immature canine heart

The electrophysiologic effects of incremental doses of intravenous amiodarone were studied in the intact neonatal canine heart and were compared with the responses observed in the adult. Seven neonatal puppies aged 5 to 14 days, and 6 adult dogs were studied. Assessment of sinus and atrioventricular (AV) nodal function and atrial and ventricular refractory periods was performed using standard His bundle recording techniques and programmed extrastimulation before and after doses of 2.5, 5 and 10 mg/kg of intravenous amiodarone. Amiodarone depressed sinus node cycle length, sinus node recovery time and AV nodal conduction in both groups. Atrial and ventricular refractory periods were also prolonged in a dose-dependent fashion in both the neonatal and adult dogs. Although similar responses to amiodarone were observed in both groups, the immature dogs were more sensitive to amiodarone in prolongation of atrial refractory periods and depression of sinus node recovery time. The neonatal group, however, demonstrated more resistance to amiodarone-induced depression of AV nodal conduction. Thus, intravenous amiodarone produces dose-dependent electrophysiologic changes in the neonate similar to those in the adult, although the significant differences in drug sensitivity may be clinically important.