Regional, age-dependent, and genotype-dependent differences in ventricular action potential duration and activation time in 410 Langendorff-perfused mouse hearts

被引:0
作者
Christoph Waldeyer
Larissa Fabritz
Lisa Fortmueller
Joachim Gerss
Dierk Damke
Andreas Blana
Sandra Laakmann
Nina Kreienkamp
Daniela Volkery
Günter Breithardt
Paulus Kirchhof
机构
[1] University Hospital Muenster,Department of Cardiology and Angiology
[2] Interdisciplinary Center for Clinical Research,Department of Medical Informatics and Biomathematics
[3] University Hospital Muenster,Medizinische Klinik und Poliklinik C, Kardiologie und Angiologie
[4] Universitätsklinikum Münster,undefined
来源
Basic Research in Cardiology | 2009年 / 104卷
关键词
Transgenic models; Action potential; Mouse; Repolarization; Aging; Genotype; Arrhythmia; Sex;
D O I
暂无
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学科分类号
摘要
Although numerous studies have reported the effects of genetic alterations on murine electrophysiology, the range of normal values for ventricular activation, repolarization, and arrhythmias in mouse hearts is not known. We analyzed right ventricular (RV), left ventricular (LV), and septal activation times, monophasic action potential durations (APD), and right ventricular effective refractory periods during spontaneous rhythm, induced AV nodal block, right ventricular pacing (100–300 ms paced cycle length), and programmed stimulation in 410 beating, Langendorff-perfused, wild-type mouse hearts of CD1, DBAC3H, FVBN, C57/Bl6, and hybrid backgrounds (age 203 ± 132 days). Action potential duration was longer at longer cycle lengths. LV-APD prolonged more than RV-APD, resulting in an increased heterogeneity of APD at longer pacing cycle lengths. Higher heart weight/body weight ratio and DBAC3H and FVB/N backgrounds were associated with long APD, C57Bl/6 background was associated with short APD. Activation times were longer in older hearts. There were no clear-cut sex-dependent APD differences. Sustained spontaneous arrhythmias occurred in 1% of hearts, non-sustained arrhythmias in 18%. Induction of AV block and C57Bl/6 genetic background were associated with spontaneous arrhythmias. Programmed stimulation induced arrhythmias in 51% of hearts. Inducible arrhythmias were associated with advanced age and shorter refractory periods. Ventricular APD in beating mouse hearts show rate- and site-dependent changes comparable to man and large animals. Bradycardia provokes spontaneous arrhythmias in mouse heart, while age-dependent conduction slowing and short refractory periods predispose to induced arrhythmias. Genetic background influences repolarization and arrhythmogenesis. These findings provide systematic data for the design and interpretation of arrhythmia studies in murine disease models.
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页码:523 / 533
页数:10
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