In Vivo Restoration of Myocardial Conduction With Carbon Nanotube Fibers.


Journal

Circulation. Arrhythmia and electrophysiology
ISSN: 1941-3084
Titre abrégé: Circ Arrhythm Electrophysiol
Pays: United States
ID NLM: 101474365

Informations de publication

Date de publication:
08 2019
Historique:
entrez: 13 8 2019
pubmed: 14 8 2019
medline: 9 4 2020
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 31401852
doi: 10.1161/CIRCEP.119.007256
pmc: PMC6858663
mid: NIHMS1533004
doi:

Substances chimiques

Carbon Fiber 0
Nanotubes, Carbon 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e007256

Subventions

Organisme : NHLBI NIH HHS
ID : K08 HL130587
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151508
Pays : United States

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Auteurs

Mark D McCauley (MD)

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.).
CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.).
Department of Medicine, Baylor College of Medicine (M.D.M., B.G., M.R.), Houston.
Departments of Medicine (Section of Cardiology), Bioengineering, and Physiology and Biophysics, University of Illinois at Chicago, College of Medicine (M.D.M., S.P.).
Jesse Brown Veterans Affairs Medical Center (M.D.M., S.P.).

Flavia Vitale (F)

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.).
Department of Neurology, Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia (F.V.).

J Stephen Yan (JS)

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.).
Department of Bioengineering, Rice Univerisity, Houston, TX (J.S.Y.).

Colin C Young (CC)

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.).

Brian Greet (B)

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.).
CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.).
Department of Medicine, Baylor College of Medicine (M.D.M., B.G., M.R.), Houston.

Marco Orecchioni (M)

Department of Chemistry and Pharmacy, University of Sassari, Italy (M.O., L.G.D.).
Division of Inflammation Biology, La Jolla Institute for Immunology, CA (M.O.).

Srikanth Perike (S)

Departments of Medicine (Section of Cardiology), Bioengineering, and Physiology and Biophysics, University of Illinois at Chicago, College of Medicine (M.D.M., S.P.).
Jesse Brown Veterans Affairs Medical Center (M.D.M., S.P.).

Abdelmotagaly Elgalad (A)

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.).
CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.).

Julia A Coco (JA)

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.).

Mathews John (M)

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.).

Doris A Taylor (DA)

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.).
CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.).

Luiz C Sampaio (LC)

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.).
CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.).

Lucia G Delogu (LG)

Department of Chemistry and Pharmacy, University of Sassari, Italy (M.O., L.G.D.).
Instituto di Ricerca Pediatrica, Fondazione Citta Della Speranza, Padova, Italy (L.G.D.).

Mehdi Razavi (M)

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.).
CHI-Baylor St. Luke's Medical Center (M.D.M., B.G., A.E., D.A.T., L.C.S., M.R.).
Department of Medicine, Baylor College of Medicine (M.D.M., B.G., M.R.), Houston.

Matteo Pasquali (M)

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.).

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Classifications MeSH