COMPARISON OF SHOCK-INDUCED DAMAGE BY DIFFERENT WAVEFORMS ASSESSED BY SPONTANEOUS CONTRACTIONS IN RAT MYOCYTES

Introduction: Application of high-intensity electric fields to the heart is the only effective therapy against ventricular fibrillation. However, it can cause injury in the cell membrane. Objective: The focus of this study was to investigate the aggressiveness of a single high-intensity stimulus with different waveforms applied to isolated rat ventricular myocytes. Methods: The experimental protocol was approved by institutional Committee for Ethics in Animal Use (protocol nº 5470-1/2020). The tested biphasic waveforms were: a) a waveform similar to those generated by a particular commercially available defibrillator, with exponential decay in the first phase and a flat second phase (EXF); b) a truncated exponential waveform similar to those delivered by most defibrillators (EXP); c) ascending ramp (ASC), which has been recently tested in some studies and d) square pulses (SQR), delivered by an electrical stimulator specifically designed for this purpose. The damage to the membrane (transient electroporation) was assessed as the rate of spontaneous contractions (rSC) during the first minute after a shock with amplitude equal to 12x the stimulation threshold. Duration of the shock-induced injury was assessed as the time for rSC to decay by half of its initial value (t1/2), estimated from monoexponential fit to the rSC values determined during 3 min after the shock. rSC was measured with the aid of a software, developed by our team, capable of monitoring myocyte shortening in recorded video files. Results: The average rSC during the first minute after a EXF shock (mean [95% confidence interval] = 44.8 [35.5, 57.0] min-1; N=28) was higher than after EXP and SQR (30.5 [24.3, 38.3] min-1 and 19.0 [12.1, 28.8] min-1, respectively; N=28, p< 0.01). The t1/2 after EXF (3.53 [2.44, 4.63] min) was greater than after EXP and ASC (1.74 [0.82, 2.67] min and 1.70 [1.24, 2.15] min, respectively, p< 0.05). Conclusion: The EXF waveform apparently causes a greater level of damage than the other tested configurations in isolated cardiomyocytes, as concluded from the stronger spontaneous activity immediately after the shock, which also took longer to subside.
This work was supported by Financiadora de Estudos e Projetos (FINEP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant n° 304017/2022).