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.
Bibliographical noteFunding Information:
This study was supported by the National Institutes of Health grants P01 HL78931, R01 HL78932, 58533, and 71140; the University of California Tobacco Related Disease Research Program (14IT-0001); American Heart Association Grant-in-Aid, Western States Affiliate (0255937Y and 0555057Y); a National Scientist Development Grant (0335308N); an Established Investigator Award (#0540093N); Kawata, Laubisch, Price, and Medtronic-Zipes Endowments; and a Chun Hwang Fellowship for Cardiac Arrhythmia Honoring Dr. Asher Kimchi, Los Angeles, California. Medtronic, St. Jude, and Cryocath have donated equipment to our research laboratory. Dr. Chen is a consultant to Medtronic Inc. However, this paper did not include any data on commercial products or advocate off-label use of drugs or equipment.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine