What is the clinical evidence from this study?

Study design: Other. Population: Ventricular arrhythmias (n=24). Intervention: α-Alumina nanoparticles vs. Double-distilled water. Primary outcome: QTc interval (p=<0.001).

What question did this study set out to answer?

The study aims to explore the electrophysiological mechanisms and crystal phase-dependent effects of alumina nanoparticles on cardiac function.

July 12, 2026BMC Cardiovascular Disorders0 citationsOpen Access

Alumina nanoparticles-induced reduction in Ito, f contributes to the occurrence of ventricular arrhythmias

Q: What are the key findings of this study?

α-Alumina nanoparticles significantly prolonged QTc intervals to 119.53 ms and reduced Ito,f current density by 81.8%, contributing to the occurrence of ventricular arrhythmias.

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

The study aims to explore the electrophysiological mechanisms and crystal phase-dependent effects of alumina nanoparticles on cardiac function.

HDHaoze DengSoochow University MXMengdie XiaSoochow University YLYiyang LiAir Force Engineering University

Key Result

α-Alumina nanoparticles significantly prolonged QTc intervals to 119.53 ms and reduced Ito,f current density by 81.8%, contributing to the occurrence of ventricular arrhythmias.

Key Points

The study aims to explore the electrophysiological mechanisms and crystal phase-dependent effects of alumina nanoparticles on cardiac function.
Intraperitoneal injection of aluminum oxide nanoparticles in rats at 100 mg/kg.
Exposure of neonatal rat ventricular myocytes to nanoparticle concentrations of 20–100 µg/mL.
Utilization of electrocardiography, monophasic action potential recording, and patch-clamp electrophysiology for analysis.
α-Al₂O₃-NPs prolonged QT intervals by 23.34% (119.53 ± 9.59 ms; p < 0.001).
MAPD₉₀ increased significantly in the α-Al₂O₃-NPs group (187.6 ± 4.9 ms; p < 0.001).
I to, f current density was inhibited by 81.8% at 100 µg/mL of α-Al₂O₃-NPs (p < 0.001).

Structured PICO

Population

24 male Sprague-Dawley rats and neonatal rat ventricular myocytes were exposed to alumina nanoparticles to assess acute cardiotoxicity and electrophysiological changes.

Intervention

α-, γ-, and mix-phase Al₂O₃-NPs via intraperitoneal injection (100 mg/kg) in rats and exposure (20–100 µg/mL) in NRVMs

Comparator

Control group

Outcome

Electrocardiographic abnormalities (QT intervals, arrhythmia scores), monophasic action potential duration (MAPD90), Ito,f current density, and ultrastructural damagesurrogate

Alpha-phase alumina nanoparticles induce QT prolongation and ventricular arrhythmias in rats, likely mediated by the inhibition of Ito,f currents.

Main Result

Absolute Event Rate: 119.53% vs 96.92%

p-value: p=<0.001

Limitations

The intraperitoneal dose of 100 mg/kg was an acute challenge dose and does not reproduce environmental or occupational human exposure levels.
Intraperitoneal administration was used, which may not reflect pulmonary or gastrointestinal absorption pathways.
In vitro concentrations (20-100 μg/mL) were used for mechanistic evaluation and are not direct equivalents of environmental exposure levels.

Abstract

Aluminum oxide nanoparticles (Al₂O₃-NPs) are currently widely applied, although they are known to induce electrocardiographic abnormalities, their crystal phase-dependent effects (including α- and γ-phases) and underlying electrophysiological mechanisms remain unclear. Cardiac injury of α-, γ-, and mix-phase Al₂O₃-NPs was investigated via intraperitoneal injection (100 mg/kg) in rats and exposure (20–100 µg/mL) in neonatal rat ventricular myocytes (NRVMs). Multidimensional analyses included electrocardiography (ECG), monophasic action potential (MAP) recording, patch-clamp electrophysiology (I to, f current), and transmission electron microscopy (TEM). α-Al₂O₃-NPs significantly prolonged QT intervals (119.53 ± 9.59 ms, increased by 23.34%; p < 0.001) and elevated arrhythmia scores (2.6 ± 0.6 vs. 0 in controls; p < 0.01), whereas γ-Al₂O₃-NPs showed no such effects. The monophasic action potential duration at 90% repolarization (MAPD₉₀) in the α-Al₂O₃-NPs group was 187.6 ± 4.9 ms, which was significantly increased compared with the control group ( p < 0.001). α-Al₂O₃-NPs were found to inhibit I to, f current density in a dose-dependent manner, with a significant reduction of 81.8% observed at 100 µg/mL ( p < 0.001). Ultrastructural damage (myofibril disorganization, mitochondrial cristae fragmentation) and intracellular accumulation of nanoparticles were observed in α-Al₂O₃-NPs group by TEM, with no observed effects for γ-Al₂O₃-NPs. Alumina nanoparticles exhibit crystal phase-dependent cardiotoxicity. α-Al₂O₃-NPs induce QT prolongation, MAPD prolongation, ventricular arrhythmias, and ultrastructural damage in rat hearts. In parallel, α-Al₂O₃-NPs suppress Ito, f currents in cultured neonatal rat ventricular myocytes. These findings suggest that Ito, f inhibition may contribute, to the electrophysiological abnormalities induced by α-Al₂O₃-NPs and provide new insights into the potential mechanisms underlying nanoparticle-induced ventricular arrhythmias.

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