Parameter-dependent modulation of cardiomyocyte metabolic activity by microsecond circular pulsed electric fields

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Cellular Electrophysiology

Background:

• Pulsed-field ablation (PFA) is a novel cardiac arrhythmia treatment using microsecond pulsed electric fields (μsPEFs).
• Understanding μsPEFs' impact on cardiomyocyte metabolic activity and survival is crucial for optimizing PFA protocols.
• Current knowledge gaps exist regarding the precise influence of μsPEFs parameters on cellular response.

Purpose of the Study:

• To systematically investigate the effects of varying μsPEFs parameters on human cardiomyocyte metabolic activity and viability.
• To determine the influence of voltage intensity, pulse packet number, and application number on cellular response.
• To identify voltage and energy thresholds for irreversible cardiomyocyte injury.

Main Methods:

• AC16 human cardiomyocytes were exposed to μsPEFs with systematically varied voltage intensities, pulse packet numbers, and application numbers.
• Metabolic activity was assessed using CCK-8 assays at multiple time points post-exposure.
• Cell death (apoptosis and necrosis) was quantified using Annexin V-FITC/PI flow cytometry.

Main Results:

• Low-voltage μsPEFs (≤ 1400 V) caused minimal metabolic suppression with partial recovery.
• Higher voltages (≥ 1600 V) induced biphasic metabolic responses, leading to significant cell death by 24 hours.
• Increased pulse packets and applications progressively suppressed metabolic activity and reduced cardiomyocyte viability in a dose-dependent manner.

Conclusions:

• Cardiomyocyte metabolic activity and survival demonstrate a clear dose-dependent sensitivity to μsPEFs parameters.
• Distinct voltage and energy thresholds for irreversible injury were identified, highlighting the importance of precise parameter modulation.
• Findings provide critical insights for optimizing PFA protocols to enhance therapeutic efficacy and patient safety.