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Updated: Feb 14, 2026

Simultaneous Isolation and Culture of Atrial Myocytes, Ventricular Myocytes, and Non-Myocytes from an Adult Mouse Heart
Published on: June 14, 2020
Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts
Michelle L Munro1,2, Xin Shen1,3, Marie Ward1
1Department of Physiology, University of Auckland, Auckland, New Zealand.
Insights
Structural changes in heart failure (HF) impact contractile function. This study links cardiomyocyte organization and microtubule changes to force development in human heart trabeculae, revealing significant structural variability.
Area of Science:
- Cardiology
- Cell Biology
- Biomedical Engineering
Background:
- Heart failure (HF) involves impaired cardiac contractility, altered excitation-contraction (EC) coupling, and cardiomyocyte disorganization.
- Structural changes in HF include tissue fibrosis and alterations within cardiomyocytes, affecting key EC coupling components like the ryanodine receptor (RyR) and junctophilin-2 (JPH2), as well as transverse tubular system architecture.
Purpose of the Study:
- To directly correlate structural alterations with force development in ventricular trabeculae from human hearts with end-stage heart failure.
- To investigate the influence of cardiomyocyte organization and cellular structures on mechanical function in failing human hearts.
Main Methods:
- Ventricular trabeculae were excised from explanted human hearts with end-stage heart failure.
- Trabeculae underwent immediate force measurements followed by fixation, sectioning, and immuno-staining for structural analysis.
- Correlations were established between functional parameters (peak stress, time-to-peak stress) and structural metrics (myocyte cross-sectional area, JPH2 localization).
Main Results:
- Peak stress in trabeculae was highly variable and strongly correlated with myocyte cross-sectional area (MCSA), not total trabecula area.
- Cardiomyocytes exhibited microtubule densification linked via JPH2 to time-to-peak stress.
- Fractional MCSA variability in trabeculae was significantly higher than in adjacent free wall samples.
Conclusions:
- Specific structural parameters, including MCSA and microtubule organization, are implicated in the functional impairment observed in human heart failure.
- The significant structural variability within ventricular trabeculae must be considered when interpreting functional data in heart failure research.
Abstract:
Heart failure (HF) is defined by compromised contractile function and is associated with changes in excitation-contraction (EC) coupling and cardiomyocyte organisation. Tissue level changes often include fibrosis, while changes within cardiomyocytes often affect structures critical to EC coupling, including the ryanodine receptor (RyR), the associated protein junctophilin-2 (JPH2) and the transverse tubular system architecture. Using a novel approach, we aimed to directly correlate the influence of structural alterations with force development in ventricular trabeculae from failing human hearts. Trabeculae were excised from explanted human hearts in end-stage failure and immediately subjected to force measurements. Following functional experiments, each trabecula was fixed, sectioned and immuno-stained for structural investigations. Peak stress was highly variable between trabeculae from both within and between failing hearts and was strongly correlated with the cross-sectional area occupied by myocytes (MCSA), rather than total trabecula cross-sectional area. At the cellular level, myocytes exhibited extensive microtubule densification which was linked via JPH2 to time-to-peak stress. Trabeculae fractional MCSA variability was much higher than that in adjacent free wall samples. Together, these findings identify several structural parameters implicated in functional impairment in human HF and highlight the structural variability of ventricular trabeculae which should be considered when interpreting functional data.
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