In Vivo Restoration of Myocardial Conduction with Carbon Nanotube Fibers

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Project Summary / Abstract This is an application for a VA Merit Award Research Grant for Dr. Mark McCauley, a physician-scientist and staff Cardiologist/Electrophysiologist at the Jesse Brown VA Medical Center in Chicago. This award will provide Dr. McCauley with the support necessary to validate carbon nanotube fibers (CNTf) as a biocompatible, electrically conductive substance able to enhance ventricular conduction in the heart. To achieve these goals, Dr. McCauley has assembled a team of Electrophysiologists (Drs. Avitall and Razavi) and Bioengineers (Drs. Pasquali, Avitall, and Perin), who are Consultants on this application. Reduced myocardial conduction velocity (MCV) is a significant contributor to lethal cardiac arrhythmias including monomorphic ventricular tachycardia (VT) and sudden cardiac death (SCD). Due to underlying traditional coronary disease risk factors, and military-related exposures such as PTSD and agent orange, Veterans are more susceptible to developing VT and SCD. Previously, restoration of native myocardial conduction has not been possible because of lack of a biocompatible material that combines strength, fatigue- resistance, conductibility, and low impedance to charge transfer properties. Recently, CNTf have been described that combine these properties into a manufactured suture-like material. Published and preliminary data from our laboratory suggest that CNTf are capable of transferring electrical charge between electroanatomically distinct areas of myocardium, such as across ventricular scar and the AV junction. Additionally, CNTf are biocompatible materials with a unique high capacitance, low impedance material/tissue interface. The central hypothesis is that CNTf have such a low tissue-material impedance, that source-sink mismatch between electroanatomically separated tissues is sufficiently reduced to facilitate trans-myocardial conduction within cardiac tissue. To test this hypothesis, three Specific Aims are proposed: Aim 1 – Assess whether CNTf reduce source-sink mismatch across ventricular scar; Aim 2 – Determine whether CNTf increase MCV across post-infarction ventricular scar and prevent VT; Aim 3 – Determine the conductive stability, tensile strength, and inflammatory response to long- term CNTf implants. The innovation of our project is that for the first time, we are able to bridge electrically separate tissues with CNTf to facilitate trans-myocardial transfer of electrical signal. Our expected outcome from completion of the proposed Aims is an enhanced understanding of the mechanisms underlying CNTf-based electrical conduction, and the development of strong pre-clinical data necessary for the future application of CNTf to reduce adverse cardiac events in Veterans.