The Society for Heart Valve Disease



Development of a Calcification Model for Aortic Valves of Isolated Mouse Hearts

Nicole Kiesendahl1, Sabine Merten1, Svenja van Geul1, Sebastian Jansen1, Irina Moshkova2, Benita Hermanns-Sachweh3, Ulrich Steinseifer1.
1Dept. of Cardiovascular Engineering, Inst. of Applied Medical Engineering, Helmholtz Institute, RWTH University, Aachen, Germany, 2Institute for Molecular Cardiovascular Research, RWTH University Hospital, Aachen, Germany, 3Institute for Pathology, RWTH University Hospital, Aachen, Germany.

The progressive aging and tissue failure caused by calcification of the leaflets is still a main problem of bioprosthetic heart valves. In lack of reliable in vitro test methods, the calcification process and potential anti-calcification treatments are usually analyzed in vivo in large or small animals. However, studies on large animals are time and cost consuming, whereas studies on small animals are generally limited to subcutaneous implantation outside the main circulatory system. This study focuses on the development of an accelerated calcification model for aortic valves of isolated mouse hearts. It shall be used to develop appropriate calcification fluids, which generate realistic calcification structures as seen in strong calcifying Fetuin A knock-out reference mice.
The test apparatus is based on a commercial system for the isolated heart perfusion of small rodents (Langendorff Apparatus). It had to be modified, as the Langendorff concept bases on the retrograde heart perfusion via the coronaries at closed aortic valve. The modified model requires an anterograde heart perfusion via left ventricular system similar to the Working Heart Model. However, in our model an active function of the heart is not possible due to the non-physiological calcium- and phosphate-concentrations of the perfusate, which are needed to induce accelerated calcification. Thus, a pulsatile flow through the cannulated left ventricle and across the aortic valve is generated via a piston pump.
So far, we tested three different fluids with various electrolyte compositions under physiological temperature- and pH-conditions.
Test duration was 24 hours. Qualitative and quantitative analyses of the hearts are performed by histology and scanning electron microscopy.
Calcification of the aortic valves of isolated mouse hearts could be generated, depending on the fluid composition. It could be detected by von Kossa staining. Further analyses via scanning electron microscopy and a comparative evaluation of the calcifying potential of the different fluids are ongoing.
A model for a rapid calcification of aortic valves of isolated mouse hearts could be established. Further data analyses and a correlation of the calcification patterns with in vivo calcified knock-out mice have yet to be performed.
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