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HTP protocol for detection of cardiac pathologies


Reduced systolic and/or diastolic heart function can be caused by multiple cardiovascular events such as myocardial infarction, chronic hypertension or chronic valve disease. Loss of cardiomyocytes and pathological cardiac remodeling in combination with apparent clinical symptoms are summarized as heart failure (HF). HF not only results in a significant decrease in the quality of life but is also an important cause of morbidity and mortality worldwide. Still, however, the mechanisms responsible for the transition from a compensated cardiac hypertrophy to HF are still poorly understood. Therefore, there is a need to precisely assess cardiac function in preclinical models.

The protein phosphatase calcineurin was early identified as a potent inducer of the cardiac hypertrophy and its activation is associated with the transition from hypertrophy to HF. Using Calcineurin transgene (CN) mice scientists from the German Mouse Clinic 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 in awake mice and cardiac magnetic resonance (CMR) techniques. The scientists measured left and right ventricular dimensions and function, pulmonary and mitral flow pattern and the hearts electrophysiology non-invasively in less than 1 h per mouse. The novel study protocol allows the diagnosis of biventricular cardiac pathologies and to study symptom occurrence and disease progression non-invasively in high throughput (HTP).

In CN mice the scientists identified left ventricular dilation and reduced performance of CN hearts, defects in electrical conduction and right ventricular cardiomyopathy.

Moreth et al., High throughput phenotyping of left and right ventricular cardiomyopathy in calcineurin transgene mice. Int J Cardiovasc Imaging, DOI 10.1007/s10554-015-0596-z