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1 Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
2 Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA
* To whom correspondence should be addressed. E-mail: chengy{at}ccf.org.
Introduction: Investigation of the mechanisms of arrhythmia genesis and maintenance has benefited from the use of optical mapping techniques employing excitation-contraction uncouplers (ECUs). We investigated the effect of the ECUs 2,3-butanedione monoxime (BDM) and cytochalasin D (Cyto D) on the induction and maintenance of arrhythmia by electric shocks. Methods and Results: Electrical activity was optically mapped from anterior epicardium of rabbit hearts (n = 9) during shocks (-100-V, 8 ms) applied from a ventricular lead at various phases of action potential duration (APD). Restitution curves (RC) were obtained using S1S2 and APD70 protocols. Compared with Cyto D, BDM significantly shortened APD90 although no significant difference in dispersion of repolarization was observed. Wavelength also shortened in BDM. In general, shock-induced arrhythmias in BDM and Cyto D were ventricular tachycardic (VT) in nature. With respect to shock-induced sustained arrhythmias (SISA), the vulnerable window was wider and the incidence was higher under BDM than in Cyto D. There was also a difference in morphology of VT between the two agents. The arrhythmias in BDM usually resemble monomorphic VT, especially those lasting longer than 30 seconds. In contrast, arrhythmias in Cyto D more resembled polymorphic VT. However, the average number of phase singularities increased under Cyto D versus BDM while no significant difference in the dominant frequency of SISA was observed. BDM reduced the slope of RC compared with Cyto D, but duration of arrhythmia under BDM was significantly increased compared to that in Cyto D. Conclusion: BDM increased arrhythmia genesis and maintenance relative to Cyto D.
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