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1 Heart & Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH, USA
2 Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH, USA
3 Deaprtment of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
4 Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH, USA; Deaprtment of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
* To whom correspondence should be addressed. E-mail: wmills{at}metrohealth.org.
Introduction: Late myocardial infarction (MI) is associated with ventricular arrhythmias and sudden cardiac death. The exact mechanistic relationship between abnormal cellular electrophysiology, conduction abnormalities, and arrhythmogenesis associated with late MI is not completely understood. Methods and Results: We report a novel, rapid dye superfusion technique to enable whole heart, high resolution optical mapping of late MI. Optical mapping of action potentials was performed in normal rats and rats with anterior MI 7 days after left anterior descending artery ligation. Hearts from normal rats exhibited normal action potentials and impulse conduction. Using programmed stimulation to assess arrhythmia inducibility, 29% of hearts with late MI had inducible sustained ventricular tachycardia, compared to 0% in normal rats. A causal relationship between the site of infarction, abnormal action potential conduction (i.e. block, slow conduction), and arrhythmogenesis was observed. Conclusion: Optical mapping techniques can be used to measure high resolution action potentials in a whole heart model of late MI. This experimental model reproduces many of the electrophysiological characteristics (i.e. conduction slowing, block, ventricular tachycardia) associated with MI in patients. Importantly, the results of this study can enhance our ability to understand the interplay between cellular heterogeneity, conduction abnormalities, and arrhythmogenesis associated with MI.
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