Optical Mapping of Cardiac Electromechanics in the In Vivo Setting

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Heart contraction is triggered by a wave of electrical depolarization that propagates through the myocardium. Optical mapping is a fluorescence-based technology for tracking electrical waves as they move through the heart. It is advantageous relative to electrode-based technology in that it images transmembrane potential, rather than extracellular potential, and therefore provides information on electrical recovery, which is a key factor in many dangerous arrhythmias. It also typically has higher spatial resolution than electrical mapping and is not adversely affected by strong electrical stimuli. Because of these advantages, optical mapping has become a mainstay of experimental cardiac electrophysiology research. However, traditional optical mapping has a major disadvantage: because of artifacts caused by cardiac motion, it is typically used in ex vivo hearts in which contraction is pharmacologically arrested. This has precluded its use clinically and in in vivo animal preparations. It has also limited optical mapping’s application to purely electrophysiological questions—important questions in cardiology that involve the bidirectional electromechanical interactions in the heart cannot be addressed when mechanical function has been abolished. Some of this limitation was recently removed by the introduction of a novel method that uses a combination of motion tracking and multi-wavelength excitation to perform optical mapping in isolated beating hearts. This method simultaneously tracks electrical propagation and quantifies deformation of the myocardium due to contraction or loading. It can therefore be used for a new set of questions in cardiac physiology that cannot be directly addressed with traditional optical mapping or other technologies. However, the method still has limitations imposed by the ex vivo preparation, for example, the overly-simple mechanical loading conditions applied to the heart; the effects of autonomic denervation; and the limited oxygen carrying capacity of crystalloid solution, which may affect the heart’s metabolic state. To address these limitations, this project will take the next step and implement in vivo optical mapping: Aim 1: Engineer an optical electromechanical mapping method for use in in vivo, open-chest, large animal preparations. Epicardial motion tracking and excitation ratiometry are key components of the method. Aim 2: Validate the electromechanical measurements generated by the new method and characterize any physiological side effects. Successful completion of these aims will result in a new tool for cardiology research. A few potential applications include: preclinical evaluation of the mechanical efficacy and electrical safety of therapies for ischemic heart disease; investigation of the effects of wall stretch on normal propagation and arrhythmogenesis; investigation of the effects of mechanical loading conditions on electrical propagation; and investigation of the effects of multi-site pacing protocols on regional wall motion.