Cardiac slices as a predictive tool for arrhythmogenic potential of drugs and chemicals

Thomas Meyer1, Katharina Stuerz, Elke Guenther

  • 1Multi Channel Systems MCS GmbH, Aspenhaustr. 21, 72770 Reutlingen, Germany. meyer@multichannelsystems.com

Abstract

Insights

Cardiac slices offer a novel assay for drug-induced arrhythmia, bridging the gap between cell and organ models. This method provides a more accurate reflection of cardiac tissue function for safety pharmacology screening.

Area of Science:

  • Cardiovascular Pharmacology
  • Drug Safety Assessment
  • Tissue Engineering

Background:

  • Cardiac arrhythmia, particularly Torsade des Pointes, is a major safety concern in drug development.
  • Current cellular assays inadequately model complex multicellular arrhythmogenic mechanisms.
  • Organ-based models are costly and lack throughput for early-stage screening.

Purpose of the Study:

  • To review and describe cardiac slice assays as a bridge between cellular and organ-based safety pharmacology.
  • To compare cardiac slices with established safety pharmacological assays.
  • To highlight the utility of cardiac slices in addressing challenges in drug-induced arrhythmia detection.

Main Methods:

  • Description and review of the cardiac slice assay methodology.
  • Comparison of cardiac slices with existing in vitro and in vivo safety pharmacology models.
  • Utilizing microelectrode arrays with up to 256 electrodes for electrophysiological recordings.

Main Results:

  • Cardiac slices, established in brain research, are gaining traction in cardiac safety pharmacology.
  • Cardiac slices can be cultured and recorded over multiple days.
  • High-density electrode arrays enable detailed electrophysiological data acquisition.

Conclusions:

  • Cardiac slices effectively bridge the gap between cellular and organ-based assays in cardiac safety pharmacology.
  • This assay more accurately reflects the functional properties of a cardiac syncytium compared to single-cell assays.
  • Cardiac slices offer a promising, higher-throughput alternative for assessing drug-induced arrhythmia risk.

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