What does this research mean for the field?

Cardiac monolayers maintain electrical wave propagation even with up to 75% non-conducting cells because cardiomyocytes self-organize into branching networks, overcoming the theoretical 40% percolation threshold. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 18, 2019PLoS Computational BiologyOpen Access

Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of non-conducting cells

Q: What is the clinical evidence from this study?

Study design: Other. Population: Cardiac fibrosis (in vitro/in silico model) (n=25). Intervention: High fraction of non-conducting cells (fibroblasts) vs. Randomly distributed cells (theoretical model). Primary outcome: Percolation threshold (critical density of non-conducting cells for wave propagation failure).

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Key result

Cardiac monolayers maintained electrical wave propagation with up to 75% non-conducting cells due to cardiomyocyte self-organization into branching networks, exceeding the 40% theoretical threshold.

Why the study?

The precise cellular mechanisms enabling electrical wave propagation through fibrotic cardiac tissue with a high percentage of fibroblasts (65-75%) remain poorly understood.

Population

Neonatal rat cardiac monolayers and virtual cardiac tissue

Design

Joint in vitro-in silico experimental and computer simulation study

Authors

NKNina KudryashovaLeiden University Medical Center ANAygul NizamievaTa Solutions (China)VTValeriya TsvelayaMinistry of Health of the Russian Federation

Discussion

Member takes

Implication

Hypothesis-generating for fibrotic conduction in vivo; does not support changes to clinical thresholds or models.

Structured PICO

Population

Neonatal rat ventricular cardiomyocytes mixed with cardiac fibroblasts in variable proportion (20-88% fibroblasts) (n=25 monolayers) and virtual cardiac tissue monolayers.

Intervention

In vitro and in silico modeling of high-density non-conducting cells (fibroblasts) with cytoskeleton alignment.

Comparator

Geometric analysis of randomly distributed conducting and non-conducting cells (classic mathematical models) and computational models without cytoskeleton alignment.

Outcome

Percolation threshold (critical density of non-conducting cells causing connectivity loss).surrogate

Main Result

Absolute Event Rate: 75% vs 40%

Cardiac tissue can maintain electrical conduction even with up to 75% non-conducting fibrotic cells due to the self-organization of cardiomyocytes into branching networks via cytoskeleton alignment.

Limitations

Experiments were conducted with 2D cell cultures, which differ from real 3D cardiac tissue.
The study did not take the extracellular matrix (collagen deposition) into account.
Other conducting cell types in the heart, such as myofibroblasts and macrophages, were not considered.
The study did not consider scaling of the percolation threshold with sample size.

Cite This Study

Kudryashova et al. (2019) studied Cardiac fibrosis (in vitro/in silico model) (n=25). High fraction of non-conducting cells (fibroblasts) vs. Randomly distributed cells (theoretical model) was evaluated on Percolation threshold (critical density of non-conducting cells for wave propagation failure). Cardiac monolayers maintained electrical wave propagation with up to 75% non-conducting cells due to cardiomyocyte self-organization into branching networks, exceeding the 40% theoretical threshold.

synapsesocial.com/papers/6a164116a2d9d2b88ec50d59 https://doi.org/10.1371/journal.pcbi.1006597

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Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of non-conducting cells

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of non-conducting cells

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider