Mapping of reentrant spontaneous polymorphic ventricular tachycardia in a Scn5a+/- mouse model

被引:30
|
作者
Martin, Claire A. [1 ]
Guzadhur, Laila [2 ]
Grace, Andrew A. [2 ]
Lei, Ming [3 ]
Huang, Christopher L. -H. [1 ]
机构
[1] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England
[2] Univ Cambridge, Dept Biochem, Cambridge CB2 3EG, England
[3] Univ Manchester, Sch Clin & Lab Sci, Cardiovasc Grp, Manchester M13 9PL, Lancs, England
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2011年 / 300卷 / 05期
基金
英国惠康基金; 英国医学研究理事会;
关键词
Brugada Syndrome; transgenic mouse; arrhythmia; conduction; BRUGADA-SYNDROME; OUTFLOW TRACT; CELLULAR BASIS; ST ELEVATION; CONDUCTION; REPOLARIZATION; MECHANISMS; ARRHYTHMOGENESIS; TACHYARRHYTHMIAS; HETEROGENEITIES;
D O I
10.1152/ajpheart.00034.2011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Martin CA, Guzadhur L, Grace AA, Lei M, Huang CL. Mapping of reentrant spontaneous polymorphic ventricular tachycardia in a Scn5a+/- mouse model. Am J Physiol Heart Circ Physiol 300: H1853-H1862, 2011. First published March 4, 2011; doi:10.1152/ajpheart.00034.2011.-Two major mechanisms have been postulated for the arrhythmogenic tendency observed in Brugada Syndrome (BrS): delays in conduction or increased heterogeneities in repolarization. We use a contact mapping system to directly investigate the interacting roles of these two mechanisms in arrhythmogenesis using a genetic murine model for BrS for the first time. Electrograms were obtained from a multielectrode recording array placed against the left ventricle and right ventricle (RV) of spontaneously beating Langendorff-perfused wild type (WT) and Scn5a+/- mouse hearts. Scn5a+/- hearts showed activation waves arriving at the epicardial surface consistent with slowed conduction, which was exacerbated in the presence of flecainide. Lines of conduction block across the RV resulting from premature ventricular beats led to the formation of reentrant circuits and polymorphic ventricular tachycardia. WT hearts showed an inverse relationship between activation times and activation recovery intervals measured at the epicardial surface, which resulted in synchronicity of repolarization times. In contrast, Scn5a+/- hearts, despite having smaller mean activation recovery intervals, demonstrated a greater heterogeneity compared with WT. Isochronal maps showed that their normal activation recovery interval gradients at the epicardial surface were disrupted, leading to heterogeneity in repolarization times. We thus directly demonstrate the initiation of arrhythmia in the RV of Scn5a+/- hearts. This occurs as a result of the combination of repolarization heterogeneities leading to lines of conduction block and unidirectional conduction, with conduction slowing allowing the formation of reentrant circuits. The repolarization heterogeneities may also be responsible for the changing pattern of block, leading to the polymorphic character of the resulting ventricular tachycardia.
引用
收藏
页码:H1853 / H1862
页数:10
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