The canine model with chronic, complete atrio-ventricular block

被引:71
作者
Oros, Avram [1 ]
Beekman, Jet D. M. [1 ]
Vos, Marc A. [1 ]
机构
[1] UMC Utrecht, Div Heart & Lungs, Dept Med Physiol, NL-3584 CM Utrecht, Netherlands
关键词
hypertrophy and electrical remodeling; ventricular arrhythmias and sudden cardiac death; drug-induced Torsades de Pointes; acquired long-QT syndrome; beat-to-beat variability of repolarization;
D O I
10.1016/j.pharmthera.2008.03.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Proarrhythmic susceptibility to drug-induced Torsades de Pointes is restricted to individuals with a predisposed phenotype characterized by a reduced repolarization reserve. Additional factors are often involved in a further impairment of repolarization, possibly culminating with dangerous ventricular polymorphic tachyarrhythmias. Drugs that block repolarizing currents represent such an additional hit. The dog model with chronic, complete atrio-ventricular block has been used frequently for proarrhythmic drug screening. The ventricular remodeling seen after ablation of the AV node enhances the susceptibility for repolarization-dependent arrhythmias. In this review, we I) describe the cellular and molecular basis of ventricular remodeling, 2) validate the CAVB dog as a drug screening model and 3) introduce a new surrogate predictive proarrhythmic parameter: beat-to-beat variability of repolarization. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:168 / 178
页数:11
相关论文
共 111 条
[1]   Cardiac channelopathies: it's in the genes [J].
Ackerman, MJ .
NATURE MEDICINE, 2004, 10 (05) :463-464
[2]   Unique topographical distribution of m cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome [J].
Akar, FG ;
Yan, GX ;
Antzelevitch, C ;
Rosenbaum, DS .
CIRCULATION, 2002, 105 (10) :1247-1253
[3]  
Antoons G, 2005, J MOL CELL CARDIOL, V39, P195
[4]   Cellular basis for triggered ventricular arrhythmias that occur in the setting of compensated hypertrophy and heart failure: considerations for diagnosis and treatment [J].
Antoons, Gudrun ;
Oros, Avram ;
Bito, Virginie ;
Sipido, Karin R. ;
Vos, Marc A. .
JOURNAL OF ELECTROCARDIOLOGY, 2007, 40 (06) :S8-S14
[5]   Window Ca2+ current and its modulation by Ca2+ release in hypertrophied cardiac myocytes from dogs with chronic atrioventricular block [J].
Antoons, Gudrun ;
Volders, Paul G. A. ;
Stankovicova, Tania ;
Bito, Virginie ;
Stengl, Milan ;
Vos, Marc A. ;
Sipido, Karin R. .
JOURNAL OF PHYSIOLOGY-LONDON, 2007, 579 (01) :147-160
[6]  
Antzelevitch C, 1997, J ELECTROCARDIOL, V30, P168
[7]   Inhibition of cardiac potassium currents by pentobarbital [J].
Bachmann, A ;
Mueller, S ;
Kopp, K ;
Brueggemann, A ;
Suessbrich, H ;
Gerlach, U ;
Busch, AE .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2002, 365 (01) :29-37
[8]   Cardiac excitation-contraction coupling [J].
Bers, DM .
NATURE, 2002, 415 (6868) :198-205
[9]   Interaction of different potassium channels in cardiac repolarization in dog ventricular preparations:: role of repolarization reserve [J].
Biliczki, P ;
Virág, L ;
Iost, N ;
Papp, JG ;
Varró, A .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 137 (03) :361-368
[10]   LONG-TERM OBSERVATION OF ATRIAL AND VENTRICULAR RATES IN THE UNANESTHETIZED DOG WITH COMPLETE ATRIOVENTRICULAR-BLOCK [J].
BOUCHER, M ;
DUBRAY, C ;
DUCHENEMARULLAZ, P .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1982, 395 (04) :341-343