Abstract

BackgroundGenetically manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. It is therefore important to identify animal models that closely mimic physiological and pathological human cardiac function.MethodsIn-vivo phase contrast cardiovascular magnetic resonance (CMR) was used to measure regional three-directional left ventricular myocardial motion with high temporal resolution in mice (N=18), rabbits (N=8), and humans (N=20). Radial, long-axis, and rotational myocardial velocities were acquired in left ventricular basal, mid-ventricular, and apical short-axis locations.ResultsRegional analysis revealed different patterns of motion: 1) In humans and rabbits, the apex showed slower radial velocities compared to the base. 2) Significant differences within species were seen in the pattern of long-axis motion. Long-axis velocities during systole were fairly homogeneously distributed in mice, whereas humans showed a dominant component in the lateral wall and rabbits in the base. 3) Rotational velocities and twist showed the most distinct patterns in both temporal evolution and relative contribution of base, mid-ventricle and apex, respectively. Interestingly, a marked difference in rotational behavior during early-systole was found in mice, which exhibited clockwise rotation in all slice locations compared to counter-clockwise rotation in rabbits and humans.ConclusionsPhase contrast CMR revealed subtle, but significantly different regional myocardial motion patterns in mice, rabbits and humans. This finding has to be considered when investigating myocardial motion pattern in small animal models of heart disease.

Highlights

  • Manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases

  • A marked difference in rotational behavior during early-systole was found in mice, which exhibited clockwise rotation in all slice locations compared to counter-clockwise rotation in rabbits and humans

  • The ratio of myocardial mass and volumes between rabbits and mice (~50-100) is 2–4 times higher compared to the ratio between humans and rabbits (~25)

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Summary

Introduction

Manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. The use of normal, surgically and genetically manipulated small animal models for basic cardiac research is based on three fundamental assumptions: (a) mechanics and function of the heart are comparable across species under baseline conditions; (b) disease models have to be informative the same phenotype across models; (c) one can project from one to another species, in spite of mammalians, their short reproduction times, and their well-defined genome, mice have become a species of choice in cardiovascular research. The use of different transgenic animal models in basic cardiovascular research prompts a detailed investigation of cardiac mechanics on a regional level of the normal animal heart compared to the healthy human heart to identify animal models that closely mimic physiological human cardiac function, before using the most suitable models to investigate pathological cardiac function

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