Mark D McCauley1,2,3,4,5, Flavia Vitale6,7, J Stephen Yan6,8, Colin C Young6, Brian Greet1,2,3, Marco Orecchioni9,10, Srikanth Perike4,5, Abdelmotagaly Elgalad1,2, Julia A Coco6, Mathews John1, Doris A Taylor1,2, Luiz C Sampaio1,2, Lucia G Delogu9,11, Mehdi Razavi1,2,3, Matteo Pasquali6. 1. Electrophysiology Clinical Research and Innovation, Regenerative Medicine Research, and Cullen Cardiovascular Surgery Research, Texas Heart Institute (M.D.M., B.G., A.E., M.J., D.A.T., L.C.S., M.R.). 2. CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.). 3. Department of Medicine, Baylor College of Medicine (M.D.M., B.G., M.R.), Houston. 4. Departments of Medicine (Section of Cardiology), Bioengineering, and Physiology and Biophysics, University of Illinois at Chicago, College of Medicine (M.D.M., S.P.). 5. Jesse Brown Veterans Affairs Medical Center (M.D.M., S.P.). 6. Departments of Chemical and Biomolecular Engineering, Chemistry, and Materials Science and NanoEngineering, The Smalley-Curl Institute, Rice University, Houston, TX (F.V., J.S.Y., C.C.Y., J.A.C., M.P.). 7. Department of Neurology, Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia (F.V.). 8. Department of Bioengineering, Rice Univerisity, Houston, TX (J.S.Y.). 9. Department of Chemistry and Pharmacy, University of Sassari, Italy (M.O., L.G.D.). 10. Division of Inflammation Biology, La Jolla Institute for Immunology, CA (M.O.). 11. Instituto di Ricerca Pediatrica, Fondazione Citta Della Speranza, Padova, Italy (L.G.D.).
Abstract
BACKGROUND: Impaired myocardial conduction is the underlying mechanism for re-entrant arrhythmias. Carbon nanotube fibers (CNTfs) combine the mechanical properties of suture materials with the conductive properties of metals and may form a restorative solution to impaired myocardial conduction. METHODS: Acute open chest electrophysiology studies were performed in sheep (n=3). Radiofrequency ablation was used to create epicardial conduction delay after which CNTf and then silk suture controls were applied. CNTfs were surgically sewn across the right atrioventricular junction in rodents, and acute (n=3) and chronic (4-week, n=6) electrophysiology studies were performed. Rodent toxicity studies (n=10) were performed. Electrical analysis of the CNTf-myocardial interface was performed. RESULTS: In all cases, the large animal studies demonstrated improvement in conduction velocity using CNTf. The acute rodent model demonstrated ventricular preexcitation during sinus rhythm. All chronic cases demonstrated resumption of atrioventricular conduction, but these required atrial pacing. There was no gross or histopathologic evidence of toxicity. Ex vivo studies demonstrated contact impedance significantly lower than platinum iridium. CONCLUSIONS: Here, we show that in sheep, CNTfs sewn across epicardial scar acutely improve conduction. In addition, CNTf maintain conduction for 1 month after atrioventricular nodal ablation in the absence of inflammatory or toxic responses in rats but only in the paced condition. The CNTf/myocardial interface has such low impedance that CNTf can facilitate local, downstream myocardial activation. CNTf are conductive, biocompatible materials that restore electrical conduction in diseased myocardium, offering potential long-term restorative solutions in pathologies interrupting efficient electrical transduction in electrically excitable tissues.
BACKGROUND:Impaired myocardial conduction is the underlying mechanism for re-entrant arrhythmias. Carbon nanotube fibers (CNTfs) combine the mechanical properties of suture materials with the conductive properties of metals and may form a restorative solution to impaired myocardial conduction. METHODS: Acute open chest electrophysiology studies were performed in sheep (n=3). Radiofrequency ablation was used to create epicardial conduction delay after which CNTf and then silk suture controls were applied. CNTfs were surgically sewn across the right atrioventricular junction in rodents, and acute (n=3) and chronic (4-week, n=6) electrophysiology studies were performed. Rodent toxicity studies (n=10) were performed. Electrical analysis of the CNTf-myocardial interface was performed. RESULTS: In all cases, the large animal studies demonstrated improvement in conduction velocity using CNTf. The acute rodent model demonstrated ventricular preexcitation during sinus rhythm. All chronic cases demonstrated resumption of atrioventricular conduction, but these required atrial pacing. There was no gross or histopathologic evidence of toxicity. Ex vivo studies demonstrated contact impedance significantly lower than platinum iridium. CONCLUSIONS: Here, we show that in sheep, CNTfs sewn across epicardial scar acutely improve conduction. In addition, CNTf maintain conduction for 1 month after atrioventricular nodal ablation in the absence of inflammatory or toxic responses in rats but only in the paced condition. The CNTf/myocardial interface has such low impedance that CNTf can facilitate local, downstream myocardial activation. CNTf are conductive, biocompatible materials that restore electrical conduction in diseased myocardium, offering potential long-term restorative solutions in pathologies interrupting efficient electrical transduction in electrically excitable tissues.
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