Superiority of Biphasic Over Monophasic Defibrillation Shocks Is Attributable to Less Intracellular Calcium Transient Heterogeneity

Objectives The purpose of this study was to test the hypothesis that superiority of biphasic waveform (BW) over monophasic waveform (MW) defibrillation shocks is attributable to less intracellular calcium (Cai) transient heterogeneity. Background The mechanism by which BW shocks have a higher defibrillation efficacy than MW shocks remains unclear. Methods We simultaneously mapped epicardial membrane potential (Vm) and Cai during 6-ms MW and 3-ms/3-ms BW shocks in 19 Langendorff-perfused rabbit ventricles. After shock, the percentage of depolarized area was plotted over time. The maximum (peak) post-shock values (VmP and CaiP, respectively) were used to measure heterogeneity. Higher VmP and CaiP imply less heterogeneity. Results The defibrillation thresholds for BW and MW shocks were 288 ± 99 V and 399 ± 155 V, respectively (p = 0.0005). Successful BW shocks had higher VmP (88 ± 9%) and CaiP (70 ± 13%) than unsuccessful MW shocks (VmP 76 ± 10%, p < 0.001; CaiP 57 ± 8%, p < 0.001) of the same shock strength. In contrast, for unsuccessful BW and MW shocks of the same shock strengths, the VmP and CaiP were not significantly different. The MW shocks more frequently created regions of low Cai surrounded by regions of high Cai (post-shock Cai sinkholes). The defibrillation threshold for MW and BW shocks became similar after disabling the sarcoplasmic reticulum (SR) with thapsigargin and ryanodine. Conclusions The greater efficacy of BW shocks is directly related to their less heterogeneous effects on shock-induced SR Ca release and Cai transients. Less heterogeneous Cai transients reduces the probability of Cai sinkhole formation, thereby preventing the post-shock reinitiation of ventricular fibrillation.