What is the clinical evidence from this study?

Population: Atrial fibrillation (n=25). Intervention: Myeloperoxidase (MPO) vs. Control (vehicle). Primary outcome: Conduction velocity in neonatal rat ventricular myocyte (NRVM) monolayers (p=<0.0001).

What does this research mean for the field?

Myeloperoxidase exposure promotes arrhythmogenic structural and electrophysiological remodeling by reducing inward rectifier potassium current, depolarizing resting membrane potentials, and causing heterogeneous conduction slowing that favors reentrant arrhythmias. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

August 15, 2026BMC MedicineOpen Access

Myeloperoxidase induces arrhythmogenic structural and electrophysiological remodeling: implications for atrial fibrillation

Q: What are the key findings of this study?

Myeloperoxidase exposure significantly reduced conduction velocity (14.7 vs. 20.9 cm/s, p<0.0001) and depolarized resting membrane potentials, promoting structural and electrophysiological remodeling that favors reentrant arrhythmias.

Q: What does this research mean for the field?

Myeloperoxidase exposure promotes arrhythmogenic structural and electrophysiological remodeling by reducing inward rectifier potassium current, depolarizing resting membrane potentials, and causing heterogeneous conduction slowing that favors reentrant arrhythmias. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether myeloperoxidase induces arrhythmogenic structural and electrophysiological remodeling in atrial tissue by altering ion channels, fibrotic microarchitecture, and tissue heterogeneity.

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Key result

Myeloperoxidase cuts conduction velocity ~30%, driving structural and electrophysiological remodeling that favors reentrant arrhythmias.

P<0.0001
n=25

Why the study?

Although myeloperoxidase accumulates in the atria in atrial fibrillation, whether it promotes arrhythmogenic structural and electrophysiological remodeling remains to be determined.

Does myeloperoxidase exposure promote arrhythmogenic structural and electrophysiological remodeling in atrial tissue and ventricular myocytes?

Key Points

To determine whether myeloperoxidase induces arrhythmogenic structural and electrophysiological remodeling in atrial tissue by altering ion channels, fibrotic microarchitecture, and tissue heterogeneity.
Cultured neonatal rat ventricular and atrial myocyte monolayers, human atrial fibroblasts, and left atrial slices from persistent atrial fibrillation patients with 1 µg/mL myeloperoxidase or control for at least 24 hours.
Assessed tissue conduction using electrical mapping, cellular electrophysiology with microelectrode and patch-clamp recordings, and fibrotic remodeling via immunohistochemistry and qPCR.
Conduction velocity decreased in myeloperoxidase-exposed rat ventricular monolayers (14.7 [2.7] vs. 20.9 [1.8] cm/s, p = 0.0001), and in human atrial slices longitudinally (18.9 [6.2] vs. 35.7 [10.3] cm/s, p = 0.004) and transversely (9 [3.3] vs. 21.7 [3.5] cm/s, p = 0.0001).
In single rat ventricular myocytes, myeloperoxidase reduced resting membrane potential (-70.3 [1.1] vs. -77.2 [3.7] mV, p = 0.0009), action potential upstroke velocity (51.9 [28.5] vs. 99.8 [41.7] V/s, p = 0.03), inward rectifier potassium current IK1 at -50 mV by 76% (p = 0.01), and KCNJ2 expression by 35% (p = 0.03).
Myeloperoxidase exposure in human atrial slices increased COL1A1 by 40% (p = 0.03) and TIMP1 by 30% (p = 0.009), forming longer collagen fibers (14.4 [1.9] vs. 11.4 [2.2] µm, p = 0.002) and a more complex fibrotic network with increased branching.

Structured PICO

Does myeloperoxidase exposure promote arrhythmogenic structural and electrophysiological remodeling in atrial tissue and ventricular myocytes?

Population

In vitro and ex vivo study utilizing neonatal rat cardiomyocytes and human left atrial slices from patients with persistent atrial fibrillation to evaluate the arrhythmogenic effects of myeloperoxidase.

Intervention

Myeloperoxidase (MPO) 1 µg/mL for at least 24 hours.

Comparator

Vehicle (milliQ) control for at least 24 hours.

Outcome

Myocardial conduction (conduction velocity), cellular electrophysiology (resting membrane potential, action potential upstroke velocity), and fibrotic remodeling (extracellular matrix gene expression, collagen deposition).surrogate

Main Result

Absolute Event Rate: 14.7% vs 20.9%

p-value: p=<0.0001

Myeloperoxidase exposure promotes arrhythmogenic structural and electrophysiological remodeling, including reduced IK1, depolarized resting membrane potential, and patchy fibrosis, suggesting it as a potential therapeutic target in atrial fibrillation.

Limitations

Complex structure of the atrial appendage resulted in some slices containing fibrofatty infiltrates or non-viable myocardial tissue.
Values of conduction heterogeneity could not be reliably established in sufficient numbers of human atrial tissue samples due to regional capture.
Cultured NRVM monolayers are isotropic, less mature, and have a lower conduction velocity than normal adult myocardium.
Limitation in acquiring all measures of interest due to smaller myocardial areas that may be disconnected in atrial appendage slices.
Values of conduction heterogeneity could not be reliably established in sufficient numbers of atrial tissue samples due to regional capture.

Discussion

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Implication

MPO antagonism should not yet alter AF practice; extends prior data to diseased human atria and leaves open inhibitor studies.

Cite This Study

Al‐Shama et al. (2026) studied Atrial fibrillation (n=25). Myeloperoxidase (MPO) vs. Control (vehicle) was evaluated on Conduction velocity in neonatal rat ventricular myocyte (NRVM) monolayers (p=<0.0001). Myeloperoxidase exposure significantly reduced conduction velocity (14.7 vs. 20.9 cm/s, p<0.0001) and depolarized resting membrane potentials, promoting structural and electrophysiological remodeling that favors reentrant arrhythmias.

synapsesocial.com/papers/6a801a0e75c2e31742c867ba https://doi.org/10.1186/s12916-026-05076-4

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Myeloperoxidase induces arrhythmogenic structural and electrophysiological remodeling: implications for atrial fibrillation

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Myeloperoxidase induces arrhythmogenic structural and electrophysiological remodeling: implications for atrial fibrillation

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Also Consider

Also Consider