Author + information
- Received March 23, 2018
- Revision received June 11, 2018
- Accepted June 13, 2018
- Published online August 29, 2018.
- Lilei Yu, MD, PhDa,b,
- Benjamin S. Scherlag, PhDc,
- Kenneth Dormer, PhDd,
- Isaac Rutel, PhDe,
- Bing Huang, MD, PhDa,b,
- Xiaoya Zhou, MD, PhDa,b,
- Aneetta E. Kuriakose, MS, BSf,
- Kytai K. Nguyen, PhDf and
- Sunny Po, MD, PhDc,∗ ()
- aDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- bCardiovascular Research Institute, Wuhan University, Wuhan, China
- cSection of Cardiovascular Diseases and Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
- dIntegrative Physiology and Pharmacology Department, College of Osteopathic Medicine, Liberty University, Lynchburg, Virginia
- eDepartment of Radiological Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
- fDepartment of Bioengineering, the University of Texas at Arlington, Arlington, Texas
- ↵∗Address for correspondence:
Dr. Sunny S. Po, Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 1200 Everett Drive, TCH-6E103, Oklahoma City, Oklahoma.
Objectives This study sought to develop a novel targeted delivery therapy to ablate the major atrial ganglionated plexi (GP) using magnetic nanoparticles carrying a CaCl2 payload.
Background Prior studies indicated the role of hyperactivity of the cardiac autonomic nervous system in the genesis of atrial fibrillation.
Methods Twenty-eight male mongrel dogs underwent a bilateral thoracotomy. CaCl2-encapsulated magnetic nanoparticles (Ca-MNP) included magnetite in a sphere of biocompatible, biodegradable poly(lactic-co-glycolic acid). A custom external electromagnet focusing the magnetic field gradient (2,600 G) on the epicardial surface of the targeted GP was used to pull Ca-MNP into and release CaCl2 within the GP. The ventricular rate slowing response to high frequency stimulation (20 Hz, 0.1 ms) of the GP was used to assess the GP function.
Results The minimal effective concentration of CaCl2 to inhibit the GP function was 0.5 mmol/l. Three weeks after CaCl2 (0.5 mmol/l, n = 18 GP) or saline (n = 18 GP) microinjection into GP, the increased GP function, neural activity, and atrial fibrillation inducibility, as well as shortened effective refractory period in response to 6 h of rapid atrial pacing (1,200 beats/min) were suppressed by CaCl2 microinjection. After intracoronary infusion of Ca-MNP, the external electromagnet pulled Ca-MNP to the targeted GP and suppressed the GP function (n = 6 GP) within 15 min.
ConclusionS Ca-MNP can be magnetically targeted to suppress GP function by calcium-mediated neurotoxicity. This novel approach may be used to treat arrhythmias related to hyperactivity of the cardiac autonomic nervous system, such as early stage of atrial fibrillation, with minimal myocardial injury.
- atrial fibrillation
- autonomic nervous system
- calcium neurotoxicity
- ganglionated plexi
- magnetic nanoparticles
Part of this study and the electromagnet were supported by NanoMed Targeting System Inc. Dr. Yu has received a grant (no. 81530011) from the National Nature Science Foundation of China. Dr. Scherlag holds a patent related to this paper; receives funding from NanoMed Targeting System; and owns stock shares of NanoMed Targeting System. Dr. Dormer holds a patent related to this paper; receives funding from NanoMed Targeting System; and owns stock shares of NanoMed Targeting System. Dr. Rutel has received funding from NanoMed Targeting Systems; serves on the Scientific Advisory Board for NanoMed Targeting Systems; and owns stock in NanoMed Targeting Systems. Dr. Po holds a patent related to this paper; receives funding from NanoMed Targeting System; owns stock shares of NanoMed Targeting System; receives research funding from NanoMed Targeting System; and has received an in-house grant of the Heart Rhythm Institute, University of Oklahoma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received March 23, 2018.
- Revision received June 11, 2018.
- Accepted June 13, 2018.
- 2018 American College of Cardiology Foundation
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