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

Abstract

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 μm 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 (APD₉₀, 169.9 ± 4 ms) and drug effects on this parameter were similar to papillary muscles. The L-type Ca-channel blocker nifedipine shortened APD₉₀ with a half maximal effective concentration (EC₅₀) of 4.5 μM. The I_Kr blocker E4031 and neuroleptic drug risperidone prolonged APD₉₀ with EC₅₀ values of 31 nM and 0.67 μM, 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.

Pip5 Transduction Peptides Direct High Efficiency Oligonucleotide-mediated Dystrophin Exon Skipping in Heart and Phenotypic Correction in mdx Mice

“…Live heart tissue slices were prepared from the left ventricle of 4-6 months mdx mice [34]. In brief, hearts were rapidly excised, ventricular tissue blocks were dissected and mounted onto the specimen holder of a high precision vibratome (7000 smz, Campden Instruments, UK), in ice-cold Tyrode solution.…”

Coagulation factor Xa induces an inflammatory signalling by activation of protease-activated receptors in human atrial tissue

“…The activated human factor X (FXa) was used in the concentration of 50 nM (Dunn, Germany). The viability of human atrial tissue slices cultured or stimulated in vivo was confirmed using established vital staining technique (CellTracker Green CMFDA, Invitrogen, Karlsruhe, Germany) (Bussek et al, 2009). The living slices were incubated for 1-2 h with the final concentration of 5 mM dye in serum-free medium and imaged as stitched mosaic with a fluorescent microscope (Zeiss Axiovert 200 m) using an excitation wavelength filter of 480/40 nm, a diachroic filter 505 nm long pass and emission wavelength between filter of 535/50 nm.…”

Influence of ischemic core muscle fibers on surface depolarization potentials in superfused cardiac tissue preparations: a simulation study

“…1), pulmonary vein sleeves, ventricular slices as well as trabeculae and papillary muscles are widely used in experiments to study the physiology of cardiac function in health and disease [5, 21, 22, 40]. Unlike in isolated myocytes, gap junctions and extracellular matrix are preserved, allowing to characterize electrophysiological function under conditions similar to those in intact hearts (see Fig.…”

“…In contrast to larger preparations, where perfusion is essential to ensure adequate oxygen supply as well as wash out of waste products throughout the preparation [47], due to its simplicity, superfusion with oxygenated solutions is typically employed for thin-walled tissue samples [5, 17, 21–23, 40]. Although superfusion is adequate to maintain preparations viable for prolonged experimental procedures, this is not the case with larger samples where the thickness of the muscle wall exceeds the diffusion length [2].…”