High throughput phenotyping of left and right ventricular cardiomyopathy in calcineurin transgene mice
| Autor: | Kristin Moreth, Luciana Caminha Afonso, Helmut Fuchs, Valérie Gailus-Durner, Hugo A. Katus, Raffi Bekeredjian, Lorenz Lehman, Martin Hrabě de Angelis |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Ventricular Dysfunction Right Mice Transgenic Ventricular Function Left Ventricular Myosins Electrocardiography Ventricular Dysfunction Left Predictive Value of Tests Animals Radiology Nuclear Medicine and imaging Genetic Predisposition to Disease Promoter Regions Genetic Heart Failure Hypertrophy Right Ventricular Myosin Heavy Chains Ventricular Remodeling Calcineurin Hemodynamics Cardiomyopathy Hypertrophic Magnetic Resonance Imaging Echocardiography Doppler High-Throughput Screening Assays Mice Inbred C57BL Disease Models Animal Phenotype Disease Progression Ventricular Function Right Female Hypertrophy Left Ventricular Cardiology and Cardiovascular Medicine |
| Zdroj: | The international journal of cardiovascular imaging. 31(4) |
| ISSN: | 1875-8312 |
| Popis: | Consistent protocols for the assessment of diastolic and systolic cardiac function to assure the comparability of existing data on preclinical models are missing. Calcineurin transgene (CN) mice are a preclinical model for hypertrophic and failing hearts. We aimed at evaluating left and right ventricular structural and functional remodeling in CN hearts with an optimized phenotyping protocol. We developed a protocol using techniques and indices comparable to those from human diagnostics for comprehensive in vivo cardiac screening using high-frequency echocardiography, Doppler, electrocardiography and cardiac magnetic resonance (CMR) techniques. We measured left and right ventricular dimensions and function, pulmonary and mitral flow pattern and the hearts electrophysiology non-invasively in1 h per mouse. We found severe biventricular dilation and a drastic decline in performance in accordance with a condition of heart failure (HF), diastolic dysfunction and defects in electrical conduction in 8-week-old calcineurin transgenic mice. Echocardiography of the left ventricle was performed with and without anesthesia. In all cases absolute values on echocardiography compared with CMR were smaller for LV dimension and wall thickness, resulting in higher fractional shorting and ejection fraction. The study protocol described here opens opportunities to assess the added value of combined echocardiography, Doppler, CMR and ECG recording techniques for the diagnosis of biventricular cardiac pathologies i.e. of HF and to study symptom occurrence and disease progression non-invasively in high-throughput. Phenotyping CN hearts revealed new symptom occurrence and allowed insights into the diverse phenotype of hypertrophic failing hearts. |
| Databáze: | OpenAIRE |
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