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Ventricular myocyte injury by high-intensity electric field: Effect of pulse duration
Luiza Ns Prado1, Jair T Goulart, Marcelo Zoccoler
1Department of Biomedical Engineering, School of Electrical and Computer Engineering, University of Campinas, São Paulo, Brazil. pedrox@ceb.unicamp.br.
Insights
High-intensity electric fields (HEF) can injure cardiac cells during defibrillation. This study found that a 0.5 ms pulse duration optimizes safety, suggesting shorter durations may improve defibrillation outcomes.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Electrophysiology
Background:
- High-intensity electric fields (HEF) are crucial for terminating ventricular fibrillation.
- HEF application can lead to cardiac cell injury.
- Understanding the relationship between HEF pulse characteristics and cell injury is vital for improving therapeutic safety.
Purpose of the Study:
- To determine the relationship between high-intensity electric fields (HEF) pulse duration and cardiomyocyte lethal injury.
- To establish strength-duration (SxD) curves for both cell lethality and excitation.
- To identify an optimal pulse duration for maximizing the stimulation safety factor (SSF).
Main Methods:
- Survival analysis was used to generate lethality curves and determine the HEF intensity required to kill 50% of cells (E50).
- Strength-duration (SxD) curves for lethality and excitation were plotted for pulse durations ranging from 0.1 ms to 70 ms.
- The stimulation safety factor (SSF) was calculated as the ratio of the SxD curve for lethality to the SxD curve for excitation.
Main Results:
- Higher HEF intensity was required for cell death with shorter pulse durations.
- The highest stimulation safety factor (SSF) was observed at a pulse duration of 0.5 ms, not the shortest duration tested.
- The defibrillation threshold is duration-dependent, with shorter durations potentially offering increased safety.
Conclusions:
- Optimizing HEF pulse duration is critical for enhancing defibrillation safety.
- A pulse duration of 0.5 ms appears to provide the greatest safety margin, balancing efficacy and cardiomyocyte injury.
- Clinical application of shorter stimulus durations, deviating from the typical 10 ms, may improve patient outcomes by increasing defibrillation safeness.
Abstract:
Although high-intensity electric fields (HEF) application is currently the only effective therapy available to terminate ventricular fibrillation, it may cause injury to cardiac cells. In this study we determined the relation between HEF pulse length and cardiomyocyte lethal injury. We obtained lethality curves by survival analysis, which were used to determine the value of HEF necessary to kill 50% of cells (E50) and plotted a strength-duration (SxD) curve for lethality with 10 different durations: 0.1, 0.2, 0.5, 1, 3, 5, 10, 20, 35 and 70 ms. For the same durations we also obtained an SxD curve for excitation and established an indicator for stimulatory safeness (stimulation safety factor - SSF) as the ratio between the SxD curve for lethality and one for excitation. We found that the lower the pulse duration, the higher the HEF intensity required to cell death. Contrary to expectations, the highest SSF value does not correspond to the lowest pulse duration but to the one of 0.5 ms. As defibrillation threshold has been described as duration-dependent, our results imply that the use of shorter stimulus duration - instead of the one typically used in the clinic (10 ms) - might increase defibrillation safeness.
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