Evaluation system of cardiac cells and tissues with combined micro-electrode array based electrical mapping and optical mapping system

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For progress of regenerative medicine in cardiology, such as bio-pacemaker based on cultured cardiac tissue for arrhythmia therapy, we need a system to evaluate function of cardiac cell, cardiac tissue, and a whole heart where the regenerated tissue is implanted. In this study, combined optical and electrical measurement system of cultured cardiac tissue and whole heart preparation has been developed.1) We have developed a cardiac electric stimulation system with real time feedback of action potential propagation dynamics. In this system, cardiac electrical propagation is visualized by optical mapping method with high spatial and temporal resolution. Propagated excitation wave front is determined in real time, and the location and timing of electrical stimulation is controlled depending on the propagation pattern. It can initiate Make/Break excitation by controlling the timing and location considering the phase (depolarized, repolarized, and resting phase) of the cardiac tissue. The function of the system was confirmed by experiments with Langendorff perfused rabbit heart preparations.2) We have also developed measurement system for cultured cardiac cells and stem cells where temporal and spatial electrical activation patterns are measured by an integrated micro-electrode arrays fabricated with photo lithography (64 channels, 30 μm X 30 μm, electrode spacing: 130 μm), and a fluorescence image of intracellular Ca is measured by a cooled CCD camera. Cardiac cells were separated from neonatal rats and cultured. mechanical contraction was observed after three days in vitro. It grows to contraction of extended areas of cultured cells. Synchronization of the electrical activities and mechanical contraction were also identified. Intracellular calcium concentration was measured by fluorescent dye (fluo-4) simultaneously. Synchronization of calcium dynamics and electrical activities were identified.