Abstract

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratome-sliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verified viability. Optically mapped transmembrane potentials confirmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.

Highlights

  • Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization

  • The availability of cardiac ventricular samples is mostly limited to trabeculae or papillary muscles from intracardiac ablation p­ rocedures[7,15,21,22] and to a reduced number of explanted failing hearts or hearts from organ donors not transplanted for technical r­ easons[6,11,15,16,19,20,23,24]

  • We present transmural core biopsies as a safe and widely available method to obtain ventricular tissues during routine cardiac surgery for structural and functional characterization

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Summary

Introduction

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically. There is a need for a higher throughput system that allows the characterization of ventricular tissue electrophysiology in health and disease, with a representation of inter- and intra-individual variability in the spatial and temporal ­domains[23,25,26,27,28]

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