title: Mitochondrial depolarization and electrophysiological changes during ischemia in the rabbit and human heart.
abstract: Instability of the inner mitochondrial membrane potential (ΔΨm) has been implicated in electrical dysfunction, including arrhythmogenesis during ischemia-reperfusion. Monitoring ΔΨm has led to conflicting results, where depolarization has been reported as sporadic and as a propagating wave. The present study was designed to resolve the aforementioned difference and determine the unknown relationship between ΔΨm and electrophysiology. We developed a novel imaging modality for simultaneous optical mapping of ΔΨm and transmembrane potential (Vm). Optical mapping was performed using potentiometric dyes on preparations from 4 mouse hearts, 14 rabbit hearts, and 7 human hearts. Our data showed that during ischemia, ΔΨm depolarization is sporadic and changes asynchronously with electrophysiological changes. Spatially, ΔΨm depolarization was associated with action potential duration shortening but not conduction slowing. Analysis of focal activity indicated that ΔΨm is not different within the myocardium where the focus originates compared with normal ventricular tissue. Overall, our data suggest that during ischemia, mitochondria maintain their function at the expense of sarcolemmal electrophysiology, but ΔΨm depolarization does not have a direct association to ischemia-induced arrhythmias.
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Sulkin
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
authors.forename: Bas J
authors.initials: BJ
authors.lastname: Boukens
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
authors.forename: Megan
authors.initials: M
authors.lastname: Tetlow
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Gutbrod
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
authors.forename: Fu Siong
authors.initials: FS
authors.lastname: Ng
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri igor@wustl.edu.
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000200:Action Potentials; D000818:Animals; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D061848:Optical Imaging / Q000379:methods; D011817:Rabbits
keywords: arrhythmia; imaging; ischemia; metabolism