比较普鲁卡因胺和伊布利特经右心房给药与静脉给药时对犬药物浓度、电生理参数及房颤终止的影响。

Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide and ibutilide are delivered into the right atrium versus intravenously.

作者信息

Vereckei A, Warman E, Mehra R, Zipes D P

机构信息

Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.

出版信息

J Cardiovasc Electrophysiol. 2001 Mar;12(3):330-6. doi: 10.1046/j.1540-8167.2001.00330.x.

DOI:10.1046/j.1540-8167.2001.00330.x

PMID:11291807

Abstract

INTRODUCTION

We tested the hypothesis that right intra-atrial (i.a.) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (AF) than intravenous (i.v.) drug delivery.

METHODS AND RESULTS

Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during i.a. and i.v. drug administration at > or = 2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 microg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during i.a. and i.v. drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between i.v. (5/7 procainamide; 4/8 ibutilide) or i.a. (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide).

CONCLUSION

Our data do not support any beneficial effect of i.a. versus i.v. procainamide or ibutilide delivery.

摘要

引言

我们检验了这样一个假说，即与静脉给药相比，右心房内（i.a.）给予抗心律失常药物会导致更高的血清药物峰值浓度、更大的电生理效应以及更高的终止心房颤动（AF）的疗效。

方法与结果

八只犬接受9.7mg/kg普鲁卡因胺输注，八只犬接受0.02mg/kg伊布利特输注，均在5分钟内注射。每只犬在i.a.和i.v.给药期间，以≥2天的间隔分别进行一次电生理（EP）研究和一次AF终止研究（各共四项研究）。在不同时间点测量右心房起搏夺获阈值、右心房有效不应期（ERP）、复极化70%和90%时的右心房和右心室单相动作电位（MAP）持续时间（MAPD70、MAPD90）、AH、HV和QT间期、QRS宽度、动脉收缩压和舒张压以及心输出量。从冠状窦和股静脉采集血样用于药物水平测定。在整个研究过程中，以400毫秒的周期长度对右心房进行起搏。通过快速右心房起搏诱发AF，并通过以1.5至3μg/kg/min输注乙酰甲胆碱来维持。在开始抗心律失常药物输注前，使持续性AF持续10分钟。我们发现i.a.和i.v.给药期间冠状窦和股静脉中普鲁卡因胺浓度无显著差异。两种给药途径之间，右心房ERP、MAPD70、MAPD90以及所有其他测量的EP参数的时间进程和增加程度没有差异。在静脉给药（5/7例普鲁卡因胺；4/8例伊布利特）或i.a.给药（3/8例普鲁卡因胺；3/8例伊布利特）之间，以及在不同药物之间（8/15例普鲁卡因胺；7/16例伊布利特），AF终止情况均未发现显著差异。