Tissue Slices from Adult Mammalian Hearts as a Model for Pharmacological Drug Testing

Aim: Isolated papillary muscles and enzymatically dissociated myocytes of guinea-pig hearts are routinely used for experimental cardiac research. The aim of our study is to investigate adult mammalian ventricular slices as an alternative preparation. Method: Vibratome cut ventricular slices (350 mu m thick) were examined histologically and with 2-photon microscopy for fibre orientation. Intracellular action potentials were recorded with conventional glass microelectrodes, extracellular potentials were measured with tungsten platinum electrodes and multi-electrode arrays (MEA). Results: Dominant direction of fibre orientation was absent in vertical and horizontal transmural slices, but was longitudinal in tangential slices. Control action potential duration (APD(90), 169.9 +/- 4 ms) and drug effects on this parameter were similar to papillary muscles. The L-type Ca-channel blocker nifedipine shortened APD(90) with a half maximal effective concentration (EC50) of 4.5 mu M. The I-Kr blocker E4031 and neuroleptic drug risperidone prolonged APD(90) with EC50 values of 31 nM and 0.67 mu M, respectively. Mapping field potentials on multi-electrode arrays showed uniform spread of excitation with a mean conduction velocity of 0.47 m.s(-1). Conclusion: Slices from adult mammalian hearts could become a useful routine model for electrophysiological and pharmacological research. Copyright (C) 2009 S. Karger AG, Basel