What question did this study set out to answer?

To determine whether cardiac myofibroblasts exert contractile forces on cardiomyocytes to impair electrical propagation via mechanoelectric feedback mechanisms.

May 3, 2011CirculationOpen Access

Mechanical Coupling Between Myofibroblasts and Cardiomyocytes Slows Electric Conduction in Fibrotic Cell Monolayers

Q: What is the clinical evidence from this study?

Population: Cardiac fibrosis (in vitro model). Intervention: Blebbistatin, gadolinium, or streptomycin vs. Untreated (control) and transforming growth factor-β-treated (fibrotic) monolayers. Primary outcome: Longitudinal conduction velocity, transverse conduction velocity, and normalized action potential upstroke velocity.

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Key result

Application of blebbistatin or mechanosensitive channel blockers to fibrotic monolayers increased longitudinal conduction velocity from 14.4 to 35.9 cm/s and transverse velocity from 4.1 to 10.3 cm/s.

Key Points

To determine whether cardiac myofibroblasts exert contractile forces on cardiomyocytes to impair electrical propagation via mechanoelectric feedback mechanisms.
Assessed optical mapping electrophysiology in TGF-β-treated (fibrotic) versus untreated cocultured monolayers of myofibroblasts and neonatal rat ventricular cells.
Evaluated conduction velocity and action potential upstroke velocity following pharmacological inhibition with blebbistatin, gadolinium, streptomycin, or connexin43 silencing.
Measured single-cell traction forces of myofibroblasts under TGF-β stimulation and channel blocker treatments.
Fibrotic monolayers exhibited significantly lower longitudinal conduction velocity (14.4 ± 0.7 vs. 27.2 ± 0.8 cm/s), transverse conduction velocity (4.1 ± 0.3 vs. 8.5 ± 0.4 cm/s), and action potential upstroke velocity (3.1 ± 0.2% vs. 4.9 ± 0.1% per ms) compared with controls.
Treatment with blebbistatin, gadolinium, or streptomycin restored longitudinal conduction velocity (35.9 ± 1.5 cm/s), transverse velocity (10.3 ± 0.6 cm/s), and upstroke velocity (4.5 ± 0.1% per ms) in fibrotic monolayers, while reducing spiral-wave inducibility.
Traction force in myofibroblasts increased with TGF-β and decreased with blebbistatin, while remaining unchanged with mechanosensitive channel blockers.

Structured PICO

Population

Monolayers of cocultured myofibroblasts and neonatal rat ventricular cells (untreated control and transforming growth factor-β-treated fibrotic)

Intervention

Application of excitation-contraction uncoupler blebbistatin or mechanosensitive channel blocker gadolinium or streptomycin

Comparator

Untreated (control) and transforming growth factor-β-treated (fibrotic) anisotropic monolayers without inhibitors

Outcome

Longitudinal conduction velocity, transverse conduction velocity, and normalized action potential upstroke velocity (dV/dt(max))surrogate

Myofibroblast-myocyte mechanical interactions impair cardiac conduction via increased mechanosensitive channel activation, suggesting a novel mechanism for arrhythmogenesis in fibrotic hearts.

Discussion

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Implication

Should not change clinical practice in fibrotic hearts; hypothesis-generating for mechanosensitive channel targeting in arrhythmogenesis.

Cite This Study

Thompson et al. (2011) studied Cardiac fibrosis (in vitro model). Blebbistatin, gadolinium, or streptomycin vs. Untreated (control) and transforming growth factor-β-treated (fibrotic) monolayers was evaluated on Longitudinal conduction velocity, transverse conduction velocity, and normalized action potential upstroke velocity. Application of blebbistatin or mechanosensitive channel blockers to fibrotic monolayers increased longitudinal conduction velocity from 14.4 to 35.9 cm/s and transverse velocity from 4.1 to 10.3 cm/s.

synapsesocial.com/papers/6a12412541f2b0889a38d19d https://doi.org/10.1161/circulationaha.110.015057

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Mechanical Coupling Between Myofibroblasts and Cardiomyocytes Slows Electric Conduction in Fibrotic Cell Monolayers

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Mechanical Coupling Between Myofibroblasts and Cardiomyocytes Slows Electric Conduction in Fibrotic Cell Monolayers

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider