Autonomic Denervation With Magnetic Nanoparticles

Article

关键词: PAROXYSMAL ATRIAL-FIBRILLATION;    GANGLIONATED PLEXI;    DRUG-DELIVERY;    SUPERPARAMAGNETIC NANOPARTICLES;    BIOMEDICAL APPLICATIONS;    EXPERIMENTAL-MODEL;    CATHETER ABLATION;    VAGAL DENERVATION;    ACRYLAMIDE;    NERVE;   

DOI  :  10.1161/CIRCULATIONAHA.110.940288

来源: SCIE

【 摘 要 】

Background-Prior studies indicated that ablation of the 4 major atrial ganglionated plexi (GP) suppressed atrial fibrillation. Methods and Results-Superparamagnetic nanoparticles (MNPs) made of Fe3O4 (core), thermoresponsive polymeric hydrogel (shell), and neurotoxic agent (N-isopropylacrylamide monomer [NIPA-M]) were synthesized. In 23 dogs, a right thoracotomy exposed the anterior right GP (ARGP) and inferior right GP (IRGP). The sinus rate and ventricular rate slowing responses to high-frequency stimulation (20 Hz, 0.1 ms) were used as the surrogate for the ARGP and IRGP functions, respectively. In 6 dogs, MNPs carrying 0.4 mg NIPA-M were injected into the ARGP. In 4 other dogs, a cylindrical magnet (2600 G) was placed epicardially on the IRGP. MNPs carrying 0.8 mg NIPA-M were then infused into the circumflex artery supplying the IRGP. The hydrogel shell reliably contracted in vitro at temperatures >= 37 degrees C, releasing NIPA-M. MNPs injected into the ARGP suppressed high-frequency stimulation-induced sinus rate slowing response (40 +/- 8% at baseline; 21 +/- 9% at 2 hours; P=0.006). The lowest voltage of ARGP high-frequency stimulation inducing atrial fibrillation was increased from 5.9 +/- 0.8 V (baseline) to 10.2 +/- 0.9 V (2 hours; P=0.009). Intracoronary infusion of MNPs suppressed the IRGP but not ARGP function (ventricular rate slowing: 57 +/- 8% at baseline, 20 +/- 8% at 2 hours; P=0.002; sinus rate slowing: 31 +/- 7% at baseline, 33 +/- 8% at 2 hours; P=0.604). Prussian Blue staining revealed MNP aggregates only in the IRGP, not the ARGP. Conclusions-Intravascularly administered MNPs carrying NIPA-M can be magnetically targeted to the IRGP and reduce GP activity presumably by the subsequent release of NIPA-M. This novel targeted drug delivery system can be used intravascularly for targeted autonomic denervation. (Circulation. 2010;122:2653-2659.)

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