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CLINICAL RESEARCH: HEART RHYTHM DISORDER

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

Gyo-Seung Hwang, MD, PhD^_*, Liang Tang, PhD, Boyoung Joung, MD, PhD, Norishige Morita, MD, PhD^_*, Hideki Hayashi, MD, PhD^_*, Hrayr S. Karagueuzian, PhD, James N. Weiss, MD, Shien-Fong Lin, PhD and Peng-Sheng Chen, MD^,_*

^_* Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California
Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana

Manuscript received December 12, 2007; revised manuscript received May 21, 2008, accepted May 27, 2008.

^_* Reprint requests and correspondence: Dr. Peng-Sheng Chen, Krannert Institute of Cardiology, 1801 N. Capitol Avenue, E475, Indianapolis, Indiana 46202 (Email: chenpp{at}iupui.edu).

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.

Key Words: electrical stimulation • polarity • resuscitation • sarcoplasmic reticulum

Abbreviations and Acronyms   APD = action potential duration   BW = biphasic waveform   Cai = intracellular calcium   CaiP = the peak (maximum) area showing higher than average intracellular calcium after shock   CaiPT = time from shock to the peak post-shock intracellular calcium   DFT50 = shock strength associated with 50% probability of successful defibrillation    = the average fluorescence level   LV = left ventricular   MW = monophasic waveform   RV = right ventricular   S1 = baseline stimulus   SR = sarcoplasmic reticulum   VF = ventricular fibrillation   VmP = the peak (maximum) area showing simultaneous depolarization of the membrane potential after shock   VmPT = time from shock to the peak area showing simultaneous depolarization of the membrane potential after shock

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