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 (Ca_i) 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 Ca_i 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 Ca_iP, respectively) were used to measure heterogeneity. Higher VmP and Ca_iP 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 Ca_iP (70 ± 13%) than unsuccessful MW shocks (VmP 76 ± 10%, p < 0.001; Ca_iP 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 Ca_iP were not significantly different. The MW shocks more frequently created regions of low Ca_i surrounded by regions of high Ca_i (post-shock Ca_i 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 Ca_i transients. Less heterogeneous Ca_i transients reduces the probability of Ca_i sinkhole formation, thereby preventing the post-shock reinitiation of ventricular fibrillation.