多非利特可降低急性心肌缺血期间室颤的发生率。一项在猪身上进行的随机研究。

Dofetilide reduces the incidence of ventricular fibrillation during acute myocardial ischaemia. A randomised study in pigs.

作者信息

Andersen H R, Wiggers H, Knudsen L L, Simonsen I, Thomsen P E, Christiansen N

机构信息

Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Denmark.

出版信息

Cardiovasc Res. 1994 Nov;28(11):1635-40. doi: 10.1093/cvr/28.11.1635.

DOI:10.1093/cvr/28.11.1635

PMID:7842456

Abstract

OBJECTIVE

The aim was to investigate whether dofetilide, a new selective cardiac potassium channel blocker, would reduce the incidence of ischaemia induced ventricular fibrillation in closed chest pigs.

METHODS

A randomised, blinded, and placebo controlled study was performed in 32 closed chest pigs with a body weight of 70-90 kg. The animals were given a dofetilide/placebo bolus of 25 micrograms.kg-1 over a 10 min period followed by a maintenance dose of 12.5 micrograms.kg-1.h-1 for the next 130 min. Electrocardiograms were recorded during sinus rhythm and during atrial pacing, before (t0) and 20 min (t20) after the beginning of drug treatment. Twenty minutes after the start of drug treatment, acute myocardial ischaemia was induced by inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon placed in the left anterior descending coronary artery proximal to the first diagonal branch. If ventricular fibrillation occurred during the 2 h ischaemia period the balloon was deflated and defibrillation attempted by dc shocks (360 joules) up to a maximum of 10 shocks.

RESULTS

Basal characteristics for the dofetilide group (n = 16) and the placebo group (n = 16) were similar: body weight 76.1(SD 5.4) kg v 75.4(4.4) kg; heart weight 296(29) g v 302(43) g; and heart rate (RR interval) 854(261) ms v 800(307) ms. During atrial pacing 100 beats.min-1 the paced QT interval (QTp) measured at t0 in the dofetilide group and the placebo group were similar, at 335(36) ms v 330(31) ms, respectively. During drug treatment (t20) the QTp interval increased to 412(38) ms in the dofetilide group (p < 0.001) whereas a much smaller increase to 341(32) ms was observed in the placebo group (p < 0.05). The heart rate and ST elevation in the two groups were similar during coronary artery occlusion. During the 2 h ischaemic period, ventricular fibrillation occurred in 6/16 (38%) of the dofetilide treated pigs, and in 13/16 (81%) of the placebo treated pigs (p < 0.01). Defibrillation was successful in 5/6 (83%) and 6/13 (46%) of the animals, respectively (p = 0.3).

CONCLUSIONS

Dofetilide significantly reduces the incidence of ischaemia induced ventricular fibrillation in closed chest pigs.

摘要

目的

旨在研究新型选择性心脏钾通道阻滞剂多非利特是否会降低闭胸猪缺血诱导性室颤的发生率。

方法

对32只体重70 - 90千克的闭胸猪进行了一项随机、双盲、安慰剂对照研究。动物在10分钟内给予25微克·千克⁻¹的多非利特/安慰剂推注剂量，随后在接下来的130分钟内给予12.5微克·千克⁻¹·小时⁻¹的维持剂量。在窦性心律和心房起搏期间，在药物治疗开始前（t0）和开始后20分钟（t20）记录心电图。药物治疗开始20分钟后，通过在第一对角支近端的左前降支冠状动脉中置入经皮冠状动脉腔内血管成形术（PTCA）球囊充气诱导急性心肌缺血。如果在2小时缺血期发生室颤，则将球囊放气，并尝试通过直流电电击（360焦耳）进行除颤，最多进行10次电击。

结果

多非利特组（n = 16）和安慰剂组（n = 16）的基础特征相似：体重76.1（标准差5.4）千克对75.4（4.4）千克；心脏重量296（29）克对302（43）克；心率（RR间期）854（261）毫秒对800（307）毫秒。在心房起搏100次/分钟时，多非利特组和安慰剂组在t0时测量的起搏QT间期（QTp）相似，分别为335（36）毫秒对330（31）毫秒。在药物治疗期间（t20），多非利特组的QTp间期增加到412（38）毫秒（p < 0.001），而安慰剂组仅增加到341（32）毫秒，增加幅度小得多（p < 0.05）。冠状动脉闭塞期间两组的心率和ST段抬高相似。在2小时缺血期，多非利特治疗的猪中有6/16（38%）发生室颤，安慰剂治疗的猪中有13/16（81%）发生室颤（p < 0.01）。除颤分别在5/6（83%）和6/13（46%）的动物中成功（p = 0.3）。结论：多非利特显著降低闭胸猪缺血诱导性室颤的发生率。