Atrial Flutter with 1:1 Atrioventricular Conduction Caused by Propafenone

We describe a case of 1:1 atrial flutter in a patient with coronary disease taking propafenone. In atrial flutter, the atrial rate is usually about 300 beciis/min with 2:1 AV conduction and a ventricular rate of 150 beats/min. Class IA antiarrhythmic drugs, especially quinidine and disopyramide, may cause 1:1 AV response because they reduce atrial rate and are vagolytic. However, propafenone is a Class IC agent and has no anticholinergic properties, and the occurrence of 1:1 AV conduction at a rate of about 250 beats/min is an important side, effect that, although uncommon, should be recognized.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

高效液相色谱法同时测定兔血清中普罗帕酮和奎尼丁的浓度

目的 :建立高效液相色谱法同时测定家兔血清普罗帕酮和奎尼丁的浓度。方法 :应用YWG -C18(5mm×150mm) ,流动相为甲醇 :醋酸钠 -醋酸缓冲液 :二乙胺 :水 (70 :24.5:0.5:5) ,紫外波长254nm检测。结果 :普罗帕酮、奎尼丁平均回收率分别为99.1 % ,97.9 % ,日内日间精密度分别为 (2.2～3.9) %,(2.6～4.4) %。结论 :方法简单、灵敏、准确 ,可用于临床治疗药物监测。     

Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (V˙_max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙_max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. Received: 25 July 1996 / Accepted: 14 October 1996     

盐酸普罗帕酮注射液细菌内毒素检查方法的确立

目的：验证盐酸普罗帕酮注射液细菌内毒素检查法的可行性。方法：通过抑制／增强试验确定盐酸普罗帕酮注射液的有效稀释浓度和细菌内毒素限值。结果：0．35mg/ml的盐酸普罗帕酮溶液无干扰作用，其内毒素限值符合规定。结论：盐酸普罗帕酮注射液可用细菌内毒素检查法来控制其细菌内毒素含量。     

心律平对房室旁道的电生理作用

应用经食道心房调搏方法观察心律平对房室旁道的电生理作用。结果显示：（１）心律平可明显延长房室旁道前向传导的有效不应期（ＥＲＰ）。（２）对心房和房室传导系统ＥＲＰ亦有延长作用。（３）可降低经旁道１：１下传心室率,并可延长经旁道道传时间和心动过速周期长度。（４）９／１２例病人持续性房室折返性心动过这终止发作,并且证实均止于旁道的逆传途径。以上资料表明心律平延长房室旁道ＥＲＰ的作用,是其治疗预激合并快速心律失常的电生理基础     

心律平治疗室性及室上性心律失常疗效分析

目的 观察心律平治疗室性及室上性心律失常的疗效及副作用。方法 对于107例经心电图及临床确诊的室性及室上性心律失常患者，按口服心律平剂量不同分为：300mg／d组(33例)、450mg/d组(66例)、600mg/d组(8例)三组，10d为1个疗程；分析心律失常类型、心律平剂量与疗效的关系、副作用及原因。结果 心律平对室性及室上性心律失常总有效率分别为89．6％与79．7％(P＞0．05)；3种剂量与疗效关系不大(P＞0．05)；发生副反应19例，占17．8％，无效17例，占15.9％。结论 心律平对室性及室上性心律失常均；有良好治疗作用，较为安全。     

普罗帕酮对钾通道亚型Kv4.2和Kv4.3电流的影响

目的　研究普罗帕酮对钾通道亚型Kv4 2和Kv4 3电流的影响。方法　采用全细胞膜片钳技术记录稳定表达Kv4 2和Kv4 3电流的人胚胎肾细胞株 (HEK2 93细胞 )电流的变化。结果　①普罗帕酮明显抑制Kv4 2和Kv4 3电流 ,呈浓度依赖性 ,IC50 分别为 1 0 3 μmol·L- 1 和 71 μmol·L- 1 ;②普罗帕酮明显加速Kv4 2和Kv4 3电流失活 ,1 0μmol·L- 1 的普罗帕酮可使Kv4 2电流衰减时间常数τ由(38 9± 2 1 )ms变为 (9 9± 1 8)ms ,半数最大失活膜电位V1 /2 由 (- 66 6± 0 8)mV左移至 (- 70 9± 1 1 )mV ;1 0 0μmol·L- 1 的普罗帕酮可使Kv4 3电流衰减时间常数τ(1 4 4 8± 2 0 8)ms变为 (1 8 5± 2 8)ms,半数最大失活膜电位V1 /2 由 (- 4 5 6± 1 9)mV左移至 (- 52 3± 2 1 )mV ;③普罗帕酮明显左移Kv4 2和Kv4 3电流的激活曲线 ,1 0μmol·L- 1 的普罗帕酮可使Kv4 2电流半数最大激活膜电位V1 /2 由 (- 4 1± 0 5)mV左移至 (- 1 6 1± 2 4)mV ;1 0 0μmol·L- 1 的普罗帕酮可使Kv4 3半数最大激活膜电位V1 /2由 (- 6 0± 1 1 )mV左移至 (- 1 6 5± 3 0 )mV。结论　普罗帕酮明显抑制Kv4 2 ,Kv4 3电流 ,该作用可能是其治疗心律失常的机制之一。     

心律平与胺碘酮治疗心律失常疗效比较的Meta分析

目的 评价文献中运用心律平与胺碘酮治疗心律失常的疗效.方法 运用计算机检索Pubmed、EMbase、Cochrane图书馆、中国生物医学文献数据库中关于心律平和胺碘酮在治疗心律失常疗效的随机对照试验,将检索时限定为2000年1月～2014年7月.对检索到的论文进行客观质量评价,应用Cochrane协作网提供的Rev Man 5.3软件进行Meta分析.结果 通过药物静脉注射给药,2组心律失常总有效率差异有统计学意义(OR=1.68,95％ CI:1.25 ～2.26,P＜0.0001);药物口服给药,2组心律失常总有效率差异有统计学意义(OR=1.49,95％ CI:1.09 ～ 2.03,P=0.010);2组不良反应发生率比较差异无统计学意义(OR=0.85,95％ CI:0.62 ～ 1.16,P＞0.05).结论 胺碘酮组治疗心率失常的疗效优于心律平,但对于药物的不良反应率并不增加.     

An Unusual Case Of Right Ventricular Outflow Tract Tachycardia

In this report, we describe an unusual case of right ventricular outflow tract (RVOT) tachycardia with episodes of repetitive monomorphic ventricular tachycardia (VT), paroxysmal sustained VT and incessant monomorphic VT of the same morphology. Diltiazem, adenosine, or metoprolol failed to interrupt these arrhythmias. However, administration of intravenous propafenone completely eliminated all ventricular ectopic activity. Electrophysiologic study performed off propafenone showed that the ventricular ectopic activity originated from a single locus at the anterior wall of the RVOT. Two radiofrequency applications at this site resulted in complete elimination of ventricular ectopic activity.