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Living cardiac tissue slices: An organotypic pseudo two-dimensional model for cardiac biophysics research.
MedLine Citation:
PMID:  25124067     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Living cardiac tissue slices, a pseudo two-dimensional (2D) preparation, have received less attention than isolated single cells, cell cultures, or Langendorff-perfused hearts in cardiac biophysics research. This is, in part, due to difficulties associated with sectioning cardiac tissue to obtain live slices. With moderate complexity, native cell-types, and well-preserved cell-cell electrical and mechanical interconnections, cardiac tissue slices have several advantages for studying cardiac electrophysiology. This potential has, thus far, mainly been explored using multi electrode arrays. Here, we combine tissue slices with optical mapping to monitor trans-membrane potential (Vm) and intracellular Ca(2+) concentration ([Ca(2+)]i). This combination opens up the possibility of studying the effects of experimental interventions upon action potential (AP) and calcium transients (CaT) dynamics in 2D, and with relatively high spatio-temporal resolution. As an intervention, we conducted proof-of-principle application of stretch. Mechanical stimulation of cardiac preparations is well-established for membrane patches, single cells and whole heart preparations. For cardiac tissue slices, is possible to apply stretch perpendicular or parallel to the dominant orientation of cells, while keeping the preparation in a constant focal plane for fluorescent imaging of in-slice functional dynamics. Slice-to-slice comparison furthermore allows one to assess transmural differences in ventricular tissue responses to mechanical challenges. We developed and tested application of axial stretch to cardiac tissue slices, using a manually-controlled stretching device, and recorded Vm and [Ca(2+)]i by optical mapping before, during, and after application of stretch. Living cardiac tissue slices, exposed to axial stretch, show an initial shortening in both AP and CaT duration upon stretch application, followed in most cases by a gradual prolongation of AP and CaT duration during stretch maintained up to 50 min. After release of sustained stretch, AP duration (APD) and CaT duration reverted to shorter values. Living cardiac tissue slices are a promising experimental model for the study of cardiac mechano-electric interactions. The methodology described here can be refined to achieve more accurate control over stretch amplitude and timing (e.g. using a computer-controlled motorised stage, or by synchronising electrical and mechanical events) and through monitoring of regional tissue deformation (e.g. adding motion tracking).
Authors:
Ken Wang; Derek Terrar; David J Gavaghan; Razik Mu-U-Min; Peter Kohl; Christian Bollensdorff
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-11
Journal Detail:
Title:  Progress in biophysics and molecular biology     Volume:  -     ISSN:  1873-1732     ISO Abbreviation:  Prog. Biophys. Mol. Biol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401233     Medline TA:  Prog Biophys Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ltd.
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