title: Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase.
abstract: Electrocardiography is an important method for evaluation and risk stratification of patients with cardiac hypertrophy. We hypothesized that the recently developed transgenic mouse model of cardiac hypertrophy (ErbB2(tg)) will display distinct ECG features, enabling WT (wild type) mice to be distinguished from transgenic mice without using conventional PCR genotyping. We evaluated more than 2000 mice and developed specific criteria for genotype determination by using cageside ECG, during which unanesthetized mice were manually restrained for less than 1 min. Compared with those from WT counterparts, the ECG recordings of ErbB2(tg) mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2(tg) data revealed significant correlation between heart weight and the ECG parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2(tg) from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes in other rodent models of cardiac hypertrophy. Furthermore, with appropriate modifications, this method might be translated for use in other species.
authors: Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors: Polina
authors: P
authors: Sysa-Shah
authors: Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, Maryland, Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark.
authors: Lars L
authors: LL
authors: Sørensen
authors: Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: M Roselle
authors: MR
authors: Abraham
authors: Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. kgabriel@jhmi.edu.
authors: Kathleen L
authors: KL
authors: Gabrielson
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D004562:Electrocardiography; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D008822:Mice, Transgenic; D010641:Phenotype; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C483804:Erbb2 protein, rat