An ex vivo platform to simulate cardiac physiology: a new dimension for therapy development and assessment.

Abstract

PURPOSE: Cardiac research and development of therapies and devices is being done with in silico models, using computer simulations, in vitro models, for example using pulse duplicators or in vivo models using animal models. These platforms, however, still show essential gaps in the study of comprehensive cardiac mechanics, hemodynamics, and device interaction. The PhysioHeart platform was developed to overcome these gaps by the ability to study cardiac hemodynamic functioning and device interaction ex vivo under in vivo conditions. METHODS: Slaughterhouse pig hearts (420 ± 30 g) were used for their morphological and physiological similarities to human hearts. Hearts were arrested, isolated and transported similar to transplantation protocols. After preparation, the hearts were connected to a special circulatory system that has been engineered using physical and medical principles. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved while hemodynamic parameters were continuously monitored. RESULTS: Normal cardiac hemodynamic performance was achieved both qualitatively, in terms of pulse waveforms, and quantitatively, in terms of average cardiac output (4 l/min) and pressures (110/75 mmHg). Cardiac performance was controlled and kept at normal levels for up to 4 hours, with only minor deterioration of hemodynamic performance. CONCLUSIONS: With the PhysioHeart platform we were able to reproduce normal physiological cardiac conditions ex vivo. The platform enables us to study, under different but controlled physiological conditions, form, function, and device interaction through monitoring of performance parameters and intra-cardiac visualization. Although the platform has been used for pig hearts, application of the underlying physical and engineering principles to physiologically comparable hearts from different origin is rather straightforward.